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Entity

Name
BRAF
Namespace
HGNC
Namespace Version
20150611
Namespace URL
https://arty.scai.fraunhofer.de/artifactory/bel/namespace/hgnc-human-genes/hgnc-human-genes-20150601.belns

Appears in Networks 23

BEL Framework Large Corpus Document v20170611

Approximately 61,000 statements. This is a modified version of the original to use namespace files hosted on Artifactory

BEL Framework Small Corpus Document v20150611

Approximately 2000 hand curated statements drawn from 57 PubMeds.

Selventa Protein Families Definitions v20150611

Selventa Protein Families and Members

Megakaryocyte Differentiation-2.0-Hs v2.0

The Megakaryocyte Differentiation network depicts the causal mechanisms involved in megakaryocyte differentiation in response to upstream signals (e.g. IL11, CXCL12, and THPO).

Senescence-2.0-Hs v2.0

The Mechanisms of Cellular Senescence network depicts the causal mechanisms that are involved in induction of senescence in non-transformed cells in response to a variety of external stimuli (including replicative senescence, stress-induced senescence, and oncogene-induced senescence). The network includes components that participate in intercellular signaling such as growth factors, chemokines, cytokines and proteases, which ultimately lead to manifestation of the senescence-associated secretory phenotype (SASP). \nReviewed during Jamboree2015

Senescence-2.0-Mm v2.0

The Mechanisms of Cellular Senescence network depicts the causal mechanisms that are involved in induction of senescence in non-transformed cells in response to a variety of external stimuli (including replicative senescence, stress-induced senescence, and oncogene-induced senescence). The network includes components that participate in intercellular signaling such as growth factors, chemokines, cytokines and proteases, which ultimately lead to manifestation of the senescence-associated secretory phenotype (SASP). \nReviewed during Jamboree2015

Senescence-2.0-Rn v2.0

The Mechanisms of Cellular Senescence network depicts the causal mechanisms that are involved in induction of senescence in non-transformed cells in response to a variety of external stimuli (including replicative senescence, stress-induced senescence, and oncogene-induced senescence). The network includes components that participate in intercellular signaling such as growth factors, chemokines, cytokines and proteases, which ultimately lead to manifestation of the senescence-associated secretory phenotype (SASP). \nReviewed during Jamboree2015

Alzheimer's Disease Knowledge Assembly v5.0.4

This knowledge assembly is specific to Alzheimer's Disease for the AETIONOMY project. It encodes the pathological mechanisms in neurons in the human brain as well as additional evidence from mice and rats. This model includes different pathways such as apoptosis signaling, calcium signaling, cholesterol homeostasis, endocytosis, GSK activation, inflammatory responses, oxidative stress of mitochondria and endoplasmic reticulum, etc. In this version, we have added additional mechanisms/pathways to describe the functional consequences of SNPs linked with genes implicated in Alzheimer's Disease through GWAS.

Colorectal Cancer Knowledge Assembly - Drugs Pathways and General Biology v1.1.0

Colorectal Cancer Knowledge Assembly with drug associations and Pathways + general CRC biology

Alzheimer's Disease Knowledge Assembly v5.0.6

This knowledge assembly is specific to Alzheimer's Disease for the AETIONOMY project. It encodes the pathological mechanisms in neurons in the human brain as well as additional evidence from mice and rats. This model includes different pathways such as apoptosis signaling, calcium signaling, cholesterol homeostasis, endocytosis, GSK activation, inflammatory responses, oxidative stress of mitochondria and endoplasmic reticulum, etc. In this version, we have added additional mechanisms/pathways to describe the functional consequences of SNPs linked with genes implicated in Alzheimer's Disease through GWAS.

Alzheimer's Disease Knowledge Assembly v5.0.9

This knowledge assembly is specific to Alzheimer's Disease for the AETIONOMY project. It encodes the pathological mechanisms in neurons in the human brain as well as additional evidence from mice and rats. This model includes different pathways such as apoptosis signaling, calcium signaling, cholesterol homeostasis, endocytosis, GSK activation, inflammatory responses, oxidative stress of mitochondria and endoplasmic reticulum, etc. In this version, we have added additional mechanisms/pathways to describe the functional consequences of SNPs linked with genes implicated in Alzheimer's Disease through GWAS.

colorectal cancer Knowledge Assembly - Drugs v1.0.1

colorectal cancer Knowledge Assembly with drug associations.

Colorectal Cancer Model v1.0.0

Colorectal Cancer Model built for i:DSem-BMBF project.

colorectal cancer Drugs resistance v1.0.1.0

colorectal cancer Knowledge Assembly with drug associations.

CRC_combined v1.1

BEL Document

Colorectal Cancer Model v2.0.0

Colorectal Cancer Model

Colorectal Cancer Model v0.0.0

Colorectal Cancer Model

Colorectal Cancer Model v2.0.3

Colorectal Cancer Model

Colorectal Cancer Model v2.0.4

Colorectal Cancer Model, uploaded by reagon

Colorectal Cancer Model v2.0.5

Colorectal Cancer Model, uploaded by reagon

Colorectal Cancer Model v2.0.6

Colorectal Cancer Model, uploaded by reagon

In-Edges 123

act(complex(SCOMP:"CK II Complex"), ma(kin)) increases act(p(HGNC:BRAF), ma(kin))

disruption of the KSR1/CK2 interaction or inhibition of CK2 activity significantly reduces the growth-factor-induced phosphorylation of C-Raf and B-Raf on the activating serine site in the negative-charge regulatory region (N-region). PubMed:17174095

Annotations
Experimental Factor Ontology (EFO)
3T3-L1 cell
NCBI Taxonomy Ids
9606
Uberon
embryonic tissue
Cell Ontology (CL)
neuron
MeSH
Cell Nucleus
Disease Ontology (DO)
lung cancer
MeSH
Sputum
MeSH
Head and Neck Neoplasms

p(HGNC:TSC2) increases act(p(HGNC:BRAF), ma(kin))

We found that tuberin expression increases p42/44 MAPK phosphorylation and B-Raf kinase activity. Short interfering RNA down-regulation of tuberin decreased the p42/44 MAPK phosphorylation and B-Raf activity. Expression of Rheb, the target of the GTPase-activating domain of tuberin, inhibited wild-type B-Raf kinase but not activated forms of B-Raf. PubMed:15150271

Annotations
Experimental Factor Ontology (EFO)
NIH-3T3 cell
NCBI Taxonomy Ids
9606
Uberon
liver
Cell Ontology (CL)
thymocyte
MeSH
Cell Nucleus
Disease Ontology (DO)
neuroblastoma

act(p(HGNC:TSC2), ma(cat)) increases act(p(HGNC:BRAF), ma(kin))

We found that tuberin expression increases p42/44 MAPK phosphorylation and B-Raf kinase activity. Short interfering RNA down-regulation of tuberin decreased the p42/44 MAPK phosphorylation and B-Raf activity. Expression of Rheb, the target of the GTPase-activating domain of tuberin, inhibited wild-type B-Raf kinase but not activated forms of B-Raf. PubMed:15150271

Annotations
Experimental Factor Ontology (EFO)
NIH-3T3 cell
NCBI Taxonomy Ids
9606
Uberon
liver
Cell Ontology (CL)
thymocyte
MeSH
Cell Nucleus
Disease Ontology (DO)
neuroblastoma

p(HGNC:PEBP1) directlyDecreases act(p(HGNC:BRAF), ma(kin))

Collectively, these results indicate that IGFBP7 inhibits BRAF-MEK-ERK signaling by inducing RKIP, which prevents BRAF from phosphorylating MEK. PubMed:18267069

Annotations
Experimental Factor Ontology (EFO)
SK-N-MC cell
NCBI Taxonomy Ids
9606
Uberon
cardiovascular system
Cell Ontology (CL)
melanocyte
MeSH
Cell Nucleus
Disease Ontology (DO)
breast cancer
MeSH
Sputum
MeSH
Head and Neck Neoplasms

act(p(HGNC:HRAS), ma(gtp)) directlyIncreases act(p(HGNC:BRAF), ma(kin))

Figure 1 | The ErbB signalling network. PubMed:11252954

Annotations
Experimental Factor Ontology (EFO)
HeLa cell
NCBI Taxonomy Ids
9606
Uberon
prostate gland
Cell Ontology (CL)
fat cell
MeSH
Cell Nucleus
Disease Ontology (DO)
breast cancer

act(p(HGNC:HRAS), ma(gtp)) directlyIncreases act(p(HGNC:BRAF), ma(kin))

In addition, we found that Rheb inhibits the association of B-Raf with H-Ras. PubMed:16803888

Annotations
Experimental Factor Ontology (EFO)
NCI-H1299 cell
NCBI Taxonomy Ids
9606
Uberon
lung
Cell Ontology (CL)
fibroblast
MeSH
Cell Membrane
Disease Ontology (DO)
liver cancer
MeSH
Sputum
MeSH
Head and Neck Neoplasms

act(p(HGNC:KRAS), ma(gtp)) directlyIncreases act(p(HGNC:BRAF), ma(kin))

Figure 1 | The ErbB signalling network. PubMed:11252954

Annotations
Experimental Factor Ontology (EFO)
HeLa cell
NCBI Taxonomy Ids
9606
Uberon
prostate gland
Cell Ontology (CL)
fat cell
MeSH
Cell Nucleus
Disease Ontology (DO)
breast cancer

p(HGNC:THPO) increases act(p(HGNC:BRAF), ma(kin))

Modified assertion PubMed:11283246

Annotations
Experimental Factor Ontology (EFO)
Dede cell
NCBI Taxonomy Ids
9606
Uberon
skeletal muscle tissue
Cell Ontology (CL)
endothelial cell
MeSH
Cell Membrane
Disease Ontology (DO)
leukemia

p(HGNC:BRAF, pmod(Ph, Ser)) directlyIncreases act(p(HGNC:BRAF), ma(kin))

GSK PI3K Phase 2, part 1: List of non-position specific phosphorylation effects on parent protein's activity, derived from existing causal assertions of position-specific phosphorylations on the parent protein activity. Other:GSK PI3K Phase 2 Temporary Phospho

Annotations
Experimental Factor Ontology (EFO)
HUVEC cell line
NCBI Taxonomy Ids
9606
Uberon
epithelium
Cell Ontology (CL)
cardiac muscle cell
MeSH
Cytoplasm
Disease Ontology (DO)
cerebrovascular disease

p(HGNC:BRAF, pmod(Ph, Ser)) directlyDecreases act(p(HGNC:BRAF), ma(kin))

GSK PI3K Phase 2, part 1: List of non-position specific phosphorylation effects on parent protein's activity, derived from existing causal assertions of position-specific phosphorylations on the parent protein activity. Other:GSK PI3K Phase 2 Temporary Phospho

Annotations
Experimental Factor Ontology (EFO)
HUVEC cell line
NCBI Taxonomy Ids
9606
Uberon
epithelium
Cell Ontology (CL)
cardiac muscle cell
MeSH
Cytoplasm
Disease Ontology (DO)
cerebrovascular disease

act(p(HGNC:NRAS), ma(gtp)) directlyIncreases act(p(HGNC:BRAF), ma(kin))

Figure 1 | The ErbB signalling network. PubMed:11252954

Annotations
Experimental Factor Ontology (EFO)
HeLa cell
NCBI Taxonomy Ids
9606
Uberon
prostate gland
Cell Ontology (CL)
fat cell
MeSH
Cell Nucleus
Disease Ontology (DO)
breast cancer

a(CHEBI:"sorafenib tosylate") directlyDecreases act(p(HGNC:BRAF), ma(kin))

from full text - Sorafenib is a potent TKI of VEGFR-2, VEGFR-3, B-RAF, and PDGFR-B PubMed:19763051

Annotations
Experimental Factor Ontology (EFO)
MCF 10A cell
NCBI Taxonomy Ids
9606
Uberon
lung
Cell Ontology (CL)
endothelial cell
MeSH
Extracellular Matrix
Disease Ontology (DO)
neuroblastoma
MeSH
Sputum
MeSH
Head and Neck Neoplasms

act(p(SFAM:"AKT Family"), ma(kin)) directlyIncreases act(p(HGNC:BRAF), ma(kin))

We show that phosphorylation of B-Raf by Akt occurs at multiple residues within its amino-terminal regulatory domain, at both the conserved and unique phosphorylation sites. The alteration of the serine residues within the Akt consensus sites to alanines results in a progressive increase in enzymatic activity in vitro and in vivo. PubMed:10869359

Annotations
Experimental Factor Ontology (EFO)
MCF7 cell
NCBI Taxonomy Ids
9606
Uberon
uterine cervix
Cell Ontology (CL)
juxtaglomerular complex cell
MeSH
Cell Membrane
Disease Ontology (DO)
leukemia

act(p(SFAM:"AKT Family"), ma(kin)) decreases act(p(HGNC:BRAF), ma(kin))

Moreover, the activity of Akt, a negative regulator of B-Raf, was decreased by calcium restriction. PubMed:15263001

Annotations
Experimental Factor Ontology (EFO)
Caco-2 cell
NCBI Taxonomy Ids
9606
Uberon
cardiac muscle tissue
Cell Ontology (CL)
cardiac muscle cell
MeSH
Cell Nucleus
Disease Ontology (DO)
gastric adenocarcinoma

p(HGNC:BRAF, var(p.Val600Glu)) directlyIncreases act(p(HGNC:BRAF), ma(kin))

From mutations file PubMed:12068308

Annotations
Experimental Factor Ontology (EFO)
Caco-2 cell
NCBI Taxonomy Ids
9606
Uberon
brain
Cell Ontology (CL)
smooth muscle cell
MeSH
Cell Nucleus
Disease Ontology (DO)
lymphoma

p(HGNC:BRAF, var(p.Val600Glu)) directlyIncreases act(p(HGNC:BRAF), ma(kin))

From mutations file PubMed:12670889

Annotations
Experimental Factor Ontology (EFO)
HCT 116 cell
NCBI Taxonomy Ids
9606
Uberon
prostate gland
Cell Ontology (CL)
muscle cell
MeSH
Cytoplasm
Disease Ontology (DO)
skin cancer

p(HGNC:BRAF, var(p.Val600Glu)) directlyIncreases act(p(HGNC:BRAF), ma(kin))

From mutations file PubMed:12778069

Annotations
Experimental Factor Ontology (EFO)
NIH-3T3 cell
NCBI Taxonomy Ids
9606
Uberon
smooth muscle tissue
Cell Ontology (CL)
type B pancreatic cell
MeSH
Cell Nucleus
Disease Ontology (DO)
multiple myeloma

p(HGNC:BRAF, var(p.Val600Glu)) directlyIncreases act(p(HGNC:BRAF), ma(kin))

From mutations file PubMed:12794760

Annotations
Experimental Factor Ontology (EFO)
HeLa cell
NCBI Taxonomy Ids
9606
Uberon
endothelium
Cell Ontology (CL)
B cell
MeSH
Cell Membrane
Disease Ontology (DO)
breast cancer

p(HGNC:BRAF, var(p.Val600Glu)) directlyIncreases act(p(HGNC:BRAF), ma(kin))

From mutations file PubMed:12819038

Annotations
Experimental Factor Ontology (EFO)
HaCaT
NCBI Taxonomy Ids
9606
Uberon
endothelium
Cell Ontology (CL)
cardiac muscle cell
MeSH
Cell Nucleus
Disease Ontology (DO)
adenocarcinoma

p(HGNC:BRAF, var(p.Val600Glu)) directlyIncreases act(p(HGNC:BRAF), ma(kin))

From mutations file PubMed:14602780

Annotations
Experimental Factor Ontology (EFO)
MIA PaCa-2 cell
NCBI Taxonomy Ids
9606
Uberon
intestine
Cell Ontology (CL)
astrocyte
MeSH
Cell Nucleus
Disease Ontology (DO)
neuroblastoma

p(HGNC:BRAF, var(p.Val600Glu)) directlyIncreases act(p(HGNC:BRAF), ma(kin))

From mutations file PubMed:14668801

Annotations
Experimental Factor Ontology (EFO)
HT-1080 cell
NCBI Taxonomy Ids
9606
Uberon
thyroid gland
Cell Ontology (CL)
neutrophil
MeSH
Cell Membrane
Disease Ontology (DO)
brain glioma

p(HGNC:BRAF, var(p.Val600Glu)) directlyIncreases act(p(HGNC:BRAF), ma(kin))

From mutations file PubMed:14734469

Annotations
Experimental Factor Ontology (EFO)
MEF cell line
NCBI Taxonomy Ids
9606
Uberon
aorta
Cell Ontology (CL)
macrophage
MeSH
Cell Nucleus
Disease Ontology (DO)
atherosclerosis

p(HGNC:BRAF, var(p.Val600Glu)) directlyIncreases act(p(HGNC:BRAF), ma(kin))

From mutations file PubMed:14961576

Annotations
Experimental Factor Ontology (EFO)
MKN-45 cell
NCBI Taxonomy Ids
9606
Uberon
endothelium
Cell Ontology (CL)
endothelial cell
MeSH
Cytoplasm
Disease Ontology (DO)
atherosclerosis

p(HGNC:BRAF, var(p.Val600Glu)) directlyIncreases act(p(HGNC:BRAF), ma(kin))

From mutations file PubMed:15009714

Annotations
Experimental Factor Ontology (EFO)
293T/17 cell
NCBI Taxonomy Ids
9606
Uberon
cardiovascular system
Cell Ontology (CL)
macrophage
MeSH
Cell Nucleus
Disease Ontology (DO)
lung cancer

p(HGNC:BRAF, var(p.Val600Glu)) directlyIncreases act(p(HGNC:BRAF), ma(kin))

From mutations file PubMed:15191558

Annotations
Experimental Factor Ontology (EFO)
MCF7 cell
NCBI Taxonomy Ids
9606
Uberon
thyroid gland
Cell Ontology (CL)
monocyte
MeSH
Cell Nucleus
Disease Ontology (DO)
lung cancer

p(HGNC:BRAF, var(p.Val600Glu)) directlyIncreases act(p(HGNC:BRAF), ma(kin))

From mutations file PubMed:15294323

Annotations
Experimental Factor Ontology (EFO)
L6 cell
NCBI Taxonomy Ids
9606
Uberon
skeletal muscle tissue
Cell Ontology (CL)
skeletal muscle satellite cell
MeSH
Cytoplasm
Disease Ontology (DO)
gastric adenocarcinoma

p(HGNC:BRAF, var(p.Val600Glu)) directlyIncreases act(p(HGNC:BRAF), ma(kin))

From mutations file PubMed:15467732

Annotations
Experimental Factor Ontology (EFO)
LNCAP cell
NCBI Taxonomy Ids
9606
Uberon
prostate gland
Cell Ontology (CL)
endothelial cell
MeSH
Extracellular Space
Disease Ontology (DO)
melanoma
MeSH
Hypercholesterolemia

p(HGNC:BRAF, var(p.Val600Glu)) directlyIncreases act(p(HGNC:BRAF), ma(kin))

From mutations file PubMed:15588860

Annotations
Experimental Factor Ontology (EFO)
MCF7 cell
NCBI Taxonomy Ids
9606
Uberon
endothelium
Cell Ontology (CL)
lymphocyte
MeSH
Cytoplasm
Disease Ontology (DO)
colon cancer
MeSH
Head and Neck Neoplasms

p(HGNC:BRAF, var(p.Val600Glu)) directlyIncreases act(p(HGNC:BRAF), ma(kin))

From mutations file PubMed:15782137

Annotations
Experimental Factor Ontology (EFO)
THP-1 cell
NCBI Taxonomy Ids
9606
Uberon
skeletal muscle tissue
Cell Ontology (CL)
T cell
MeSH
Cell Membrane
Disease Ontology (DO)
breast cancer
MeSH
Sputum
MeSH
Head and Neck Neoplasms

p(HGNC:BRAF, var(p.Val600Glu)) directlyIncreases act(p(HGNC:BRAF), ma(kin))

From mutations file PubMed:16001072

Annotations
Experimental Factor Ontology (EFO)
NIH-3T3 cell
NCBI Taxonomy Ids
9606
Uberon
lens of camera-type eye
Cell Ontology (CL)
monocyte
MeSH
Cell Nucleus
Disease Ontology (DO)
colon cancer
MeSH
Sputum
MeSH
Head and Neck Neoplasms

p(HGNC:BRAF, var(p.Val600Glu)) directlyIncreases act(p(HGNC:BRAF), ma(kin))

From mutations file PubMed:16170021

Annotations
Experimental Factor Ontology (EFO)
HeLa cell
NCBI Taxonomy Ids
9606
Uberon
lung
Cell Ontology (CL)
macrophage
MeSH
Extracellular Matrix
Disease Ontology (DO)
breast cancer
MeSH
Sputum
MeSH
Head and Neck Neoplasms

a(SCHEM:"cyclic AMP") increases act(p(HGNC:BRAF), ma(kin))

elevated cAMP levels lead to the activation of B-Raf and hence to ERK activation PubMed:14641023

Annotations
Experimental Factor Ontology (EFO)
SW480 cell
NCBI Taxonomy Ids
9606
Uberon
peritoneum
Cell Ontology (CL)
fat cell
MeSH
Cell Membrane
Disease Ontology (DO)
lung cancer

a(SCHEM:"cyclic AMP") increases act(p(HGNC:BRAF), ma(kin))

Inhibition of Akt or phosphatidylinositol 3-kinase also allowed cAMP-dependent activation of B-Raf and ERK in normal calcium. PubMed:15263001

Annotations
Experimental Factor Ontology (EFO)
Caco-2 cell
NCBI Taxonomy Ids
9606
Uberon
cardiac muscle tissue
Cell Ontology (CL)
cardiac muscle cell
MeSH
Cell Nucleus
Disease Ontology (DO)
gastric adenocarcinoma

p(HGNC:KSR2) directlyIncreases act(p(HGNC:BRAF), ma(kin))

hKSR-2 selectively inhibited the Cot-mediated activation of MEK by 60%. In contrast, hKSR-2 up-regulated the Rafmediated MEK activation by up to 70%. PubMed:12975377

Annotations
Experimental Factor Ontology (EFO)
A-431 cell
NCBI Taxonomy Ids
9606
Uberon
epithelium
Cell Ontology (CL)
monocyte
MeSH
Cell Nucleus
Disease Ontology (DO)
leukemia

act(p(SFAM:"PRKA Family"), ma(kin)) increases act(p(HGNC:BRAF), ma(kin))

Pharmacological inhibition of cAMP-dependent protein kinase (PKA) and siRNA-mediated depletion of PKA greatly reduced B-Raf activity, ERK1/2 activation, and cell proliferation in (WT)B-Raf cells PubMed:16452469

Annotations
Experimental Factor Ontology (EFO)
PC-3 cell
NCBI Taxonomy Ids
9606
Uberon
zone of skin
Cell Ontology (CL)
neuron
MeSH
Cytoplasm
Disease Ontology (DO)
non-small cell lung carcinoma
MeSH
Sputum
MeSH
Head and Neck Neoplasms

act(p(SFAM:"RAS Family"), ma(gtp)) directlyIncreases act(p(HGNC:BRAF), ma(kin))

Figure 1 | The ErbB signalling network. PubMed:11252954

Annotations
Experimental Factor Ontology (EFO)
HeLa cell
NCBI Taxonomy Ids
9606
Uberon
prostate gland
Cell Ontology (CL)
fat cell
MeSH
Cell Nucleus
Disease Ontology (DO)
breast cancer

act(p(SFAM:"RAS Family"), ma(gtp)) directlyIncreases act(p(HGNC:BRAF), ma(kin))

Protein kinase A-dependent phosphorylation of serine 43 within the regulatory domain of Raf-1 reciprocally potentiates its interaction with Rheb and decreases its interaction with H-Ras. PubMed:9001246

Annotations
Experimental Factor Ontology (EFO)
A-431 cell
NCBI Taxonomy Ids
9606
Uberon
liver
Cell Ontology (CL)
hepatocyte
MeSH
Cell Membrane
Disease Ontology (DO)
leukemia
MeSH
Sputum
MeSH
Head and Neck Neoplasms

a(SCHEM:Calcium) increases p(HGNC:BRAF)

Modified assertion PubMed:11018025

Annotations
Experimental Factor Ontology (EFO)
NIH-3T3 cell
NCBI Taxonomy Ids
9606
Uberon
heart
Cell Ontology (CL)
cardiac muscle cell
MeSH
Cytoplasm
Disease Ontology (DO)
lung cancer

p(HGNC:BRAF, pmod(Ph, Ser, 445)) directlyIncreases act(p(HGNC:BRAF), ma(kin))

78,136,143 The homologous site on B-Raf, S445, is constitutively phosphorylated, accounting for the higher basal activity of B-Raf. PubMed:16170185

Annotations
Experimental Factor Ontology (EFO)
HeLa cell
NCBI Taxonomy Ids
9606
Uberon
lung
Cell Ontology (CL)
macrophage
MeSH
Extracellular Matrix
Disease Ontology (DO)
breast cancer
MeSH
Sputum
MeSH
Head and Neck Neoplasms

act(p(SFAM:"RAS Family"), ma(gtp)) directlyIncreases act(p(HGNC:BRAF), ma(kin))

The activation of B-Raf by Ras has been less well studied; however, the interacting amino acids in the Ras-Raf interface are identical for B-Raf and C-Raf.129,130 The association of Ras with B-Raf also translocates B-Raf to the cell membrane where it is activated.124 Interestingly, a membrane-free complex of B-Raf and 14-3-3 can be activated in vitro by recombinant Ras. This is in stark contrast to A-Raf and C-Raf, which must undergo a series of phosphorylation reactions on serine and tyrosine residues in the cell membrane and cannot be activated by Ras alone.124,130 Of the Raf isoforms, B-Raf is activated first, and on stimulation by Ras, it heterodimerizes with C-Raf, the significance of which is not known.94 PubMed:16170185

Annotations
Experimental Factor Ontology (EFO)
U-937 cell
NCBI Taxonomy Ids
9606
Uberon
cardiovascular system endothelium
Cell Ontology (CL)
fibroblast
MeSH
Cytoplasm
Disease Ontology (DO)
cancer
MeSH
Muscle, Smooth, Vascular

act(p(SFAM:"RAS Family"), ma(gtp)) directlyIncreases tloc(p(HGNC:BRAF), fromLoc(MESHCS:"Intracellular Space"), toLoc(MESHCS:"Cell Membrane"))

The activation of B-Raf by Ras has been less well studied; however, the interacting amino acids in the Ras-Raf interface are identical for B-Raf and C-Raf.129,130 The association of Ras with B-Raf also translocates B-Raf to the cell membrane where it is activated.124 Interestingly, a membrane-free complex of B-Raf and 14-3-3 can be activated in vitro by recombinant Ras. This is in stark contrast to A-Raf and C-Raf, which must undergo a series of phosphorylation reactions on serine and tyrosine residues in the cell membrane and cannot be activated by Ras alone.124,130 Of the Raf isoforms, B-Raf is activated first, and on stimulation by Ras, it heterodimerizes with C-Raf, the significance of which is not known.94 PubMed:16170185

Annotations
Experimental Factor Ontology (EFO)
U-937 cell
NCBI Taxonomy Ids
9606
Uberon
cardiovascular system endothelium
Cell Ontology (CL)
fibroblast
MeSH
Cytoplasm
Disease Ontology (DO)
cancer
MeSH
Muscle, Smooth, Vascular

act(p(HGNC:RAP1A), ma(gtp)) increases act(p(HGNC:BRAF), ma(kin))

Additional support for the diverse functionality of Raf family members is provided by the disparate responses of B-Raf and C-Raf to identical stimuli, as well as the distinct messages that each isoform relays downstream to Rap1, which is a small GTPase that functions as both an activator and repressor of Raf.115 Rap1-mediated stimulation of B-Raf by cyclic adenosine monophosphate (cAMP) phosphorylates ERK, whereas stimulation of C-Raf inhibits ERK phosphorylation.115 PubMed:16170185

Annotations
Experimental Factor Ontology (EFO)
U-937 cell
NCBI Taxonomy Ids
9606
Uberon
cardiovascular system endothelium
Cell Ontology (CL)
fibroblast
MeSH
Cell Membrane
Disease Ontology (DO)
cancer
MeSH
Muscle, Smooth, Vascular

act(p(HGNC:RAP1A), ma(gtp)) directlyIncreases act(p(HGNC:BRAF), ma(kin))

Both B-Raf and C-Raf can bind to other small GTPases, most notably Rap1.115,131,132 The effector domains of Rap1 and Ras are nearly identical, but activation of these proteins produces vastly different downstream effects. Furthermore, Rap1 mediates distinct effects after binding to various Raf isoforms. The B-Raf–Rap1 complex activates B-Raf, whereas the C-Raf–Rap1 interaction does not activate C-Raf and, in fact, may be inhibitory.115,132,133 This occurs because Rap1 binds to the CRD of C-Raf with higher affinity than Ras and excludes Ras from binding. PubMed:16170185

Annotations
Experimental Factor Ontology (EFO)
U-937 cell
NCBI Taxonomy Ids
9606
Uberon
cardiovascular system endothelium
Cell Ontology (CL)
fibroblast
MeSH
Cytoplasm
Disease Ontology (DO)
cancer
MeSH
Muscle, Smooth, Vascular

path(MESHD:"Thyroid Neoplasms") positiveCorrelation act(p(HGNC:BRAF), ma(kin))

Somatic B-raf mutations were demonstrated in 60% to 70% of malignant melanomas and in moderate to high rates in carcinomas of the colon, ovary, and thyroid (papillary), implicating activating oncogenic B-raf mutations as critical promoters of these malignancies.9,14-17 PubMed:16170185

Annotations
Experimental Factor Ontology (EFO)
U-937 cell
NCBI Taxonomy Ids
9606
Uberon
cardiovascular system endothelium
Cell Ontology (CL)
fibroblast
MeSH
Cytoplasm
Disease Ontology (DO)
cancer
MeSH
Muscle, Smooth, Vascular

path(MESHD:"Ovarian Neoplasms") positiveCorrelation act(p(HGNC:BRAF), ma(kin))

Somatic B-raf mutations were demonstrated in 60% to 70% of malignant melanomas and in moderate to high rates in carcinomas of the colon, ovary, and thyroid (papillary), implicating activating oncogenic B-raf mutations as critical promoters of these malignancies.9,14-17 PubMed:16170185

Annotations
Experimental Factor Ontology (EFO)
U-937 cell
NCBI Taxonomy Ids
9606
Uberon
cardiovascular system endothelium
Cell Ontology (CL)
fibroblast
MeSH
Cytoplasm
Disease Ontology (DO)
cancer
MeSH
Muscle, Smooth, Vascular

a(CHEBI:sorafenib) directlyDecreases act(p(HGNC:BRAF), ma(kin))

Originally identified by high-throughput screening of small molecules against C-Raf kinase, sorafenib was found to be a potent competitive inhibitor of ATP binding in the catalytic domains of C-Raf, wild-type B-Raf, and V599EB-Raf mutant. PubMed:16170185

Annotations
Experimental Factor Ontology (EFO)
U-937 cell
NCBI Taxonomy Ids
9606
Uberon
cardiovascular system endothelium
Cell Ontology (CL)
fibroblast
MeSH
Cytoplasm
Disease Ontology (DO)
cancer
MeSH
Muscle, Smooth, Vascular

path(MESHD:"Colorectal Neoplasms") positiveCorrelation act(p(HGNC:BRAF), ma(kin))

Somatic B-raf mutations were demonstrated in 60% to 70% of malignant melanomas and in moderate to high rates in carcinomas of the colon, ovary, and thyroid (papillary), implicating activating oncogenic B-raf mutations as critical promoters of these malignancies.9,14-17 PubMed:16170185

Annotations
Experimental Factor Ontology (EFO)
U-937 cell
NCBI Taxonomy Ids
9606
Uberon
cardiovascular system endothelium
Cell Ontology (CL)
fibroblast
MeSH
Cytoplasm
Disease Ontology (DO)
cancer
MeSH
Muscle, Smooth, Vascular

p(HGNC:BRAF, pmod(Ph, Ser, 445)) directlyIncreases act(p(HGNC:BRAF), ma(kin))

The homologous site on B-Raf, S445, is constitutively phosphorylated, accounting for the higher basal activity of B-Raf. Ras presumably phosphorylates this site by activating PI3K. PubMed:16170185

Annotations
Experimental Factor Ontology (EFO)
U-937 cell
NCBI Taxonomy Ids
9606
Uberon
cardiovascular system endothelium
Cell Ontology (CL)
fibroblast
MeSH
Cytoplasm
Disease Ontology (DO)
cancer
MeSH
Muscle, Smooth, Vascular

path(MESHD:Melanoma) positiveCorrelation act(p(HGNC:BRAF), ma(kin))

Somatic B-raf mutations were demonstrated in 60% to 70% of malignant melanomas and in moderate to high rates in carcinomas of the colon, ovary, and thyroid (papillary), implicating activating oncogenic B-raf mutations as critical promoters of these malignancies.9,14-17 PubMed:16170185

Annotations
Experimental Factor Ontology (EFO)
U-937 cell
NCBI Taxonomy Ids
9606
Uberon
cardiovascular system endothelium
Cell Ontology (CL)
fibroblast
MeSH
Cytoplasm
Disease Ontology (DO)
cancer
MeSH
Muscle, Smooth, Vascular

p(HGNC:BRAF, var(p.Val599Glu)) directlyIncreases act(p(HGNC:BRAF), ma(kin))

V599EB-Raf possesses the hallmarks of a conventional oncogene because the kinase activity of its encoded protein is greatly elevated; it constitutively stimulates ERK in vivo in the absence of Ras activation; and it transforms NIH3T3 cells.144 PubMed:16170185

Annotations
Experimental Factor Ontology (EFO)
U-937 cell
NCBI Taxonomy Ids
9606
Uberon
cardiovascular system endothelium
Cell Ontology (CL)
fibroblast
MeSH
Cytoplasm
Disease Ontology (DO)
cancer
MeSH
Muscle, Smooth, Vascular

act(p(HGNC:RAP1A), ma(gtp)) increases act(p(HGNC:BRAF), ma(kin))

Thus, in UT7-Mpl cells, Rap1, but not Ras, can couple B-Raf to ERK activation. Other:11283246

path(MESHD:Neoplasms) association p(HGNC:BRAF)

Here, the similarities but also the differential effects of RAS and BRAF oncogenic signalling are examined and further implications in personalized cancer diagnosis and therapy are discussed. PubMed:25361007

Annotations
MeSH
Chromatin
Experimental Factor Ontology (EFO)
SW620 cell
Experimental Factor Ontology (EFO)
WiDr cell
Experimental Factor Ontology (EFO)
HCT116
Experimental Factor Ontology (EFO)
HCT15
MeSH
Neoplasms
Evidence and Conclusion Ontology
immunohistochemistry
MeSH
Colon
NCBI Taxonomy Names
Homo sapiens
NCBI Taxonomy Ids
10117

p(HGNC:TRAP1) decreases p(HGNC:BRAF)

The hypothesis that TRAP1 plays a regulatory function on the BRAF pathway, arising from the observation that BRAF levels are decreased upon TRAP1 interference, was tested in human breast and colorectal carcinoma in vitro and in vivo. PubMed:25239454

Annotations
Experimental Factor Ontology (EFO)
cell line
MeSH
Colorectal Neoplasms
MeSH
Breast Neoplasms
Evidence and Conclusion Ontology
RNAi
MeSH
Heterografts
NCBI Taxonomy Names
Homo sapiens

p(HGNC:TRAP1) association p(HGNC:BRAF)

This study shows that TRAP1 is involved in the regulation of BRAF synthesis/ubiquitination, without affecting its stability. PubMed:25239454

Annotations
Experimental Factor Ontology (EFO)
cell line
MeSH
Colorectal Neoplasms
MeSH
Breast Neoplasms
Evidence and Conclusion Ontology
RNAi
MeSH
Heterografts
NCBI Taxonomy Names
Homo sapiens

p(HGNC:TRAP1) increases p(HGNC:BRAF)

Indeed, BRAF synthesis is facilitated in a TRAP1-rich background, whereas increased ubiquitination occurs upon disruption of the TRAP1 network that correlates with decreased protein levels. PubMed:25239454

Annotations
Experimental Factor Ontology (EFO)
cell line
MeSH
Colorectal Neoplasms
MeSH
Breast Neoplasms
Evidence and Conclusion Ontology
RNAi
MeSH
Heterografts
NCBI Taxonomy Names
Homo sapiens

p(HGNC:TRAP1) association p(HGNC:BRAF)

It is worth noting that TRAP1 regulation on BRAF is conserved in human colorectal carcinomas, with the two proteins being frequently coexpressed. PubMed:25239454

Annotations
Experimental Factor Ontology (EFO)
cell line
MeSH
Colorectal Neoplasms
Evidence and Conclusion Ontology
RNAi
MeSH
Heterografts
NCBI Taxonomy Names
Homo sapiens

p(HGNC:SIRT2) association p(HGNC:BRAF)

SIRT2 loss also conferred resistance to BRAF and MEK inhibitors in BRAF mutant melanoma and KRAS mutant colon cancers, respectively. PubMed:24469059

Annotations
MeSH
Chromatin
Experimental Factor Ontology (EFO)
HCT116
MeSH
Melanoma
MeSH
Colorectal Neoplasms
Evidence and Conclusion Ontology
RNAi
MeSH
Serum
MeSH
Plasma
NCBI Taxonomy Names
Homo sapiens

bp(MESHPP:"Drug Resistance") association p(HGNC:BRAF)

Other potentially useful biomarkers of resistance to EGFR-targeted therapy in the process of clinical validation include mutations in BRAF, PTEN loss and PI3KCA mutations, nuclear factor-kappa beta(NF-Κβ) pathway activity, and expression of alternative EGFR ligands. PubMed:20718710

Annotations
MeSH
Peroxisomes
Experimental Factor Ontology (EFO)
MDAMB435
MeSH
Neoplasms
Evidence and Conclusion Ontology
point mutation
MeSH
Heterografts
NCBI Taxonomy Names
Homo sapiens
NCBI Taxonomy Ids
10117

p(HGNC:HSP90AB1) association p(HGNC:BRAF)

The HSP90 chaperone TRAP1 is translational regulator of BRAF synthesis/ubiquitination, since BRAF down-regulation, ERK signaling inhibition and delay of cell cycle progression occur upon TRAP1 silencing/inhibition. Since TRAP1 is upregulated in human colorectal carcinomas (CRCs) and involved in protection from apoptosis and as human BRAF-driven CRCs are poorly responsive to anticancer therapies, the relationship between TRAP1 regulation of mitochondrial apoptotic pathway and BRAF antiapoptotic signaling has been further evaluated. PubMed:26084290

Annotations
MeSH
Peroxisomes
Experimental Factor Ontology (EFO)
COLO205
MeSH
Colorectal Neoplasms
Evidence and Conclusion Ontology
combinatorial
MeSH
Blood Platelets
MeSH
Endothelium, Vascular
NCBI Taxonomy Names
Homo sapiens
NCBI Taxonomy Ids
10117

p(HGNC:TGFBRAP1) association p(HGNC:BRAF)

This study reports that BRAF cytoprotective signaling involves TRAP1-dependent inhibition of the mitochondrial apoptotic pathway. PubMed:26084290

Annotations
MeSH
Peroxisomes
Experimental Factor Ontology (EFO)
COLO205
MeSH
Colorectal Neoplasms
Evidence and Conclusion Ontology
combinatorial
MeSH
Blood Platelets
MeSH
Endothelium, Vascular
NCBI Taxonomy Names
Homo sapiens
NCBI Taxonomy Ids
10117

bp(GOBP:"cell cycle") association p(HGNC:BRAF)

The HSP90 chaperone TRAP1 is translational regulator of BRAF synthesis/ubiquitination, since BRAF down-regulation, ERK signaling inhibition and delay of cell cycle progression occur upon TRAP1 silencing/inhibition. Since TRAP1 is upregulated in human colorectal carcinomas (CRCs) and involved in protection from apoptosis and as human BRAF-driven CRCs are poorly responsive to anticancer therapies, the relationship between TRAP1 regulation of mitochondrial apoptotic pathway and BRAF antiapoptotic signaling has been further evaluated. PubMed:26084290

Annotations
MeSH
Peroxisomes
Experimental Factor Ontology (EFO)
COLO205
MeSH
Colorectal Neoplasms
Evidence and Conclusion Ontology
combinatorial
MeSH
Blood Platelets
MeSH
Endothelium, Vascular
NCBI Taxonomy Names
Homo sapiens
NCBI Taxonomy Ids
10117

path(MESHD:Melanoma) association p(HGNC:BRAF)

Signatures for BRAF oncogene have been revealed in melanoma. PubMed:22515520

Annotations
NCBI Taxonomy Ids
9606
Experimental Factor Ontology (EFO)
SW480
Disease Ontology (DO)
colorectal cancer
MeSH
Neoplasms

path(MESHD:"Colorectal Neoplasms") association p(HGNC:BRAF)

BRAF mutations are associated with aggressive, less-differentiated and therapy-resistant colorectal carcinoma. PubMed:25381152

Annotations
NCBI Taxonomy Ids
9606
Experimental Factor Ontology (EFO)
LoVo
Disease Ontology (DO)
colorectal cancer
MeSH
Rectal Neoplasms

p(HGNC:KRAS) negativeCorrelation p(HGNC:BRAF)

Oncogenic activation of KRAS and BRAF is mutually exclusive and occurs in approximately 40% and 10% of all CRCs, respectively. PubMed:26299805

Annotations
NCBI Taxonomy Ids
9606
Experimental Factor Ontology (EFO)
HCT116
Disease Ontology (DO)
colorectal cancer
MeSH
Gastrointestinal Neoplasms

p(HGNC:KRAS) negativeCorrelation p(HGNC:BRAF)

Oncogenic activation of KRAS and BRAF is mutually exclusive and occurs in approximately 40% and 10% of all CRCs, respectively. PubMed:26299805

Annotations
MeSH
Microtubules
Experimental Factor Ontology (EFO)
HCT116
MeSH
Gastrointestinal Neoplasms
Evidence and Conclusion Ontology
immunohistochemistry
MeSH
Plasma
NCBI Taxonomy Names
Mus musculus
Disease Ontology (DO)
colorectal cancer
NCBI Taxonomy Ids
9606

path(MESHD:Melanoma) association p(HGNC:BRAF)

Signatures for BRAF oncogene have been revealed in melanoma. PubMed:22515520

Annotations
MeSH
Microtubules
Experimental Factor Ontology (EFO)
SW480
MeSH
Neoplasms
Evidence and Conclusion Ontology
immunohistochemistry
MeSH
Plasma
NCBI Taxonomy Names
Mus musculus
Disease Ontology (DO)
colorectal cancer
NCBI Taxonomy Ids
9606

path(MESHD:"Colorectal Neoplasms") association p(HGNC:BRAF)

BRAF mutations are associated with aggressive, less-differentiated and therapy-resistant colorectal carcinoma. PubMed:25381152

Annotations
MeSH
Microtubules
Experimental Factor Ontology (EFO)
SW480
MeSH
Rectal Neoplasms
Evidence and Conclusion Ontology
immunohistochemistry
MeSH
Plasma
NCBI Taxonomy Names
Mus musculus
Disease Ontology (DO)
colorectal cancer
NCBI Taxonomy Ids
9606

path(MESHD:"Colorectal Neoplasms") association p(HGNC:BRAF)

BRAF mutations are associated with aggressive, less-differentiated and therapy-resistant colorectal carcinoma. PubMed:25381152

p(HGNC:KRAS) negativeCorrelation p(HGNC:BRAF)

Oncogenic activation of KRAS and BRAF is mutually exclusive and occurs in approximately 40% and 10% of all CRCs, respectively. PubMed:26299805

p(HGNC:SIRT2) association p(HGNC:BRAF)

SIRT2 loss also conferred resistance to BRAF and MEK inhibitors in BRAF mutant melanoma and KRAS mutant colon cancers, respectively. PubMed:24469059

Annotations
Experimental Factor Ontology (EFO)
HT-29
MeSH
Chromatin
MeSH
Melanoma
MeSH
Colorectal Neoplasms
Evidence and Conclusion Ontology
RNAi
MeSH
Tissues
NCBI Taxonomy Names
Homo sapiens
Disease Ontology (DO)
colorectal cancer
Uberon
intestinal epithelium
Cell Ontology (CL)
stem cell
NCBI Taxonomy Ids
10090

bp(MESHPP:"Drug Resistance") association p(HGNC:BRAF)

BRAF mutations are associated with aggressive, less-differentiated and therapy-resistant colorectal carcinoma. PubMed:25381152

Annotations
Experimental Factor Ontology (EFO)
LoVo cell
Experimental Factor Ontology (EFO)
LOVO cell
MeSH
Intracellular Space
MeSH
Rectal Neoplasms
MeSH
Mucus
NCBI Taxonomy Names
Crataegus azarolus
Disease Ontology (DO)
colorectal cancer
Uberon
intestinal epithelium
Cell Ontology (CL)
stem cell
NCBI Taxonomy Ids
9606

bp(MESHPP:"Drug Resistance") association p(HGNC:BRAF)

Other potentially useful biomarkers of resistance to EGFR-targeted therapy in the process of clinical validation include mutations in BRAF, PTEN loss and PI3KCA mutations, nuclear factor-kappa beta(NF-Κβ) pathway activity, and expression of alternative EGFR ligands. PubMed:20718710

Annotations
Experimental Factor Ontology (EFO)
HeLa cell
MeSH
Peroxisomes
MeSH
Neoplasms
Evidence and Conclusion Ontology
point mutation
MeSH
Colon
NCBI Taxonomy Names
Homo sapiens
Disease Ontology (DO)
colorectal cancer
Uberon
intestinal epithelium
Cell Ontology (CL)
stem cell
NCBI Taxonomy Ids
10090

path(MESHD:"Colorectal Neoplasms") association p(HGNC:BRAF)

BRAF mutations are associated with aggressive, less-differentiated and therapy-resistant colorectal carcinoma. PubMed:25381152

Annotations
Experimental Factor Ontology (EFO)
LoVo cell
Experimental Factor Ontology (EFO)
LOVO cell
MeSH
Intracellular Space
MeSH
Rectal Neoplasms
MeSH
Mucus
NCBI Taxonomy Names
Crataegus azarolus
Disease Ontology (DO)
colorectal cancer
Uberon
intestinal epithelium
Cell Ontology (CL)
stem cell
NCBI Taxonomy Ids
9606

p(HGNC:TRAP1) decreases p(HGNC:BRAF)

The hypothesis that TRAP1 plays a regulatory function on the BRAF pathway, arising from the observation that BRAF levels are decreased upon TRAP1 interference, was tested in human breast and colorectal carcinoma in vitro and in vivo. PubMed:25239454

Annotations
Experimental Factor Ontology (EFO)
COLO205
MeSH
Chromatin
MeSH
Colorectal Neoplasms
MeSH
Breast Neoplasms
Evidence and Conclusion Ontology
western blot
MeSH
Colon
NCBI Taxonomy Names
Homo sapiens
Disease Ontology (DO)
colorectal cancer
Uberon
intestinal epithelium
Cell Ontology (CL)
stem cell
NCBI Taxonomy Ids
10090

p(HGNC:TRAP1) association p(HGNC:BRAF)

This study shows that TRAP1 is involved in the regulation of BRAF synthesis/ubiquitination, without affecting its stability. PubMed:25239454

Annotations
Experimental Factor Ontology (EFO)
COLO205
MeSH
Chromatin
MeSH
Colorectal Neoplasms
MeSH
Breast Neoplasms
Evidence and Conclusion Ontology
western blot
MeSH
Colon
NCBI Taxonomy Names
Homo sapiens
Disease Ontology (DO)
colorectal cancer
Uberon
intestinal epithelium
Cell Ontology (CL)
stem cell
NCBI Taxonomy Ids
10090

p(HGNC:TRAP1) increases p(HGNC:BRAF)

Indeed, BRAF synthesis is facilitated in a TRAP1-rich background, whereas increased ubiquitination occurs upon disruption of the TRAP1 network that correlates with decreased protein levels. PubMed:25239454

Annotations
Experimental Factor Ontology (EFO)
COLO205
MeSH
Chromatin
MeSH
Colorectal Neoplasms
MeSH
Breast Neoplasms
Evidence and Conclusion Ontology
western blot
MeSH
Colon
NCBI Taxonomy Names
Homo sapiens
Disease Ontology (DO)
colorectal cancer
Uberon
intestinal epithelium
Cell Ontology (CL)
stem cell
NCBI Taxonomy Ids
10090

p(HGNC:TRAP1) association p(HGNC:BRAF)

It is worth noting that TRAP1 regulation on BRAF is conserved in human colorectal carcinomas, with the two proteins being frequently coexpressed. PubMed:25239454

Annotations
Experimental Factor Ontology (EFO)
COLO205
MeSH
Chromatin
MeSH
Colorectal Neoplasms
Evidence and Conclusion Ontology
western blot
MeSH
Colon
NCBI Taxonomy Names
Homo sapiens
Disease Ontology (DO)
colorectal cancer
Uberon
intestinal epithelium
Cell Ontology (CL)
stem cell
NCBI Taxonomy Ids
10090

p(HGNC:KRAS) negativeCorrelation p(HGNC:BRAF)

Oncogenic activation of KRAS and BRAF is mutually exclusive and occurs in approximately 40% and 10% of all CRCs, respectively. PubMed:26299805

p(HGNC:TGFBRAP1) association p(HGNC:BRAF)

This study reports that BRAF cytoprotective signaling involves TRAP1-dependent inhibition of the mitochondrial apoptotic pathway. PubMed:26084290

Annotations
Experimental Factor Ontology (EFO)
HT-29
MeSH
Chromatin
MeSH
Colorectal Neoplasms
Evidence and Conclusion Ontology
RNAi
MeSH
Serum
MeSH
Colon
MeSH
Heterografts
NCBI Taxonomy Names
Homo sapiens
Disease Ontology (DO)
colorectal cancer
Uberon
intestinal epithelium
Cell Ontology (CL)
stem cell
NCBI Taxonomy Ids
10090

bp(GOBP:"cell cycle") association p(HGNC:BRAF)

The HSP90 chaperone TRAP1 is translational regulator of BRAF synthesis/ubiquitination, since BRAF down-regulation, ERK signaling inhibition and delay of cell cycle progression occur upon TRAP1 silencing/inhibition. Since TRAP1 is upregulated in human colorectal carcinomas (CRCs) and involved in protection from apoptosis and as human BRAF-driven CRCs are poorly responsive to anticancer therapies, the relationship between TRAP1 regulation of mitochondrial apoptotic pathway and BRAF antiapoptotic signaling has been further evaluated. PubMed:26084290

Annotations
Experimental Factor Ontology (EFO)
HT-29
MeSH
Chromatin
MeSH
Colorectal Neoplasms
Evidence and Conclusion Ontology
RNAi
MeSH
Serum
MeSH
Colon
MeSH
Heterografts
NCBI Taxonomy Names
Homo sapiens
Disease Ontology (DO)
colorectal cancer
Uberon
intestinal epithelium
Cell Ontology (CL)
stem cell
NCBI Taxonomy Ids
10090

p(HGNC:HSP90AB1) association p(HGNC:BRAF)

The HSP90 chaperone TRAP1 is translational regulator of BRAF synthesis/ubiquitination, since BRAF down-regulation, ERK signaling inhibition and delay of cell cycle progression occur upon TRAP1 silencing/inhibition. Since TRAP1 is upregulated in human colorectal carcinomas (CRCs) and involved in protection from apoptosis and as human BRAF-driven CRCs are poorly responsive to anticancer therapies, the relationship between TRAP1 regulation of mitochondrial apoptotic pathway and BRAF antiapoptotic signaling has been further evaluated. PubMed:26084290

Annotations
Experimental Factor Ontology (EFO)
HT-29
MeSH
Chromatin
MeSH
Colorectal Neoplasms
Evidence and Conclusion Ontology
RNAi
MeSH
Serum
MeSH
Colon
MeSH
Heterografts
NCBI Taxonomy Names
Homo sapiens
Disease Ontology (DO)
colorectal cancer
Uberon
intestinal epithelium
Cell Ontology (CL)
stem cell
NCBI Taxonomy Ids
10090

path(MESHD:Melanoma) association p(HGNC:BRAF)

Signatures for BRAF oncogene have been revealed in melanoma. PubMed:22515520

Annotations
Experimental Factor Ontology (EFO)
SW480
MeSH
Intracellular Space
MeSH
Neoplasms
MeSH
Mucus
NCBI Taxonomy Names
Crataegus azarolus
Disease Ontology (DO)
colorectal cancer
Uberon
intestinal epithelium
Cell Ontology (CL)
stem cell
NCBI Taxonomy Ids
9606

path(MESHD:Neoplasms) association p(HGNC:BRAF)

Here, the similarities but also the differential effects of RAS and BRAF oncogenic signalling are examined and further implications in personalized cancer diagnosis and therapy are discussed. PubMed:25361007

Annotations
Experimental Factor Ontology (EFO)
COLO205
MeSH
Chromatin
MeSH
Neoplasms
Evidence and Conclusion Ontology
western blot
MeSH
Colon
NCBI Taxonomy Names
Homo sapiens
Disease Ontology (DO)
colorectal cancer
Uberon
intestinal epithelium
Cell Ontology (CL)
stem cell
NCBI Taxonomy Ids
10090

p(HGNC:SIRT2) association p(HGNC:BRAF)

SIRT2 loss also conferred resistance to BRAF and MEK inhibitors in BRAF mutant melanoma and KRAS mutant colon cancers, respectively. PubMed:24469059

bp(MESHPP:"Drug Resistance") association p(HGNC:BRAF)

BRAF mutations are associated with aggressive, less-differentiated and therapy-resistant colorectal carcinoma. PubMed:25381152

bp(MESHPP:"Drug Resistance") association p(HGNC:BRAF)

Other potentially useful biomarkers of resistance to EGFR-targeted therapy in the process of clinical validation include mutations in BRAF, PTEN loss and PI3KCA mutations, nuclear factor-kappa beta(NF-Κβ) pathway activity, and expression of alternative EGFR ligands. PubMed:20718710

p(HGNC:TRAP1) decreases p(HGNC:BRAF)

The hypothesis that TRAP1 plays a regulatory function on the BRAF pathway, arising from the observation that BRAF levels are decreased upon TRAP1 interference, was tested in human breast and colorectal carcinoma in vitro and in vivo. PubMed:25239454

p(HGNC:TRAP1) association p(HGNC:BRAF)

This study shows that TRAP1 is involved in the regulation of BRAF synthesis/ubiquitination, without affecting its stability. PubMed:25239454

p(HGNC:TRAP1) increases p(HGNC:BRAF)

Indeed, BRAF synthesis is facilitated in a TRAP1-rich background, whereas increased ubiquitination occurs upon disruption of the TRAP1 network that correlates with decreased protein levels. PubMed:25239454

p(HGNC:TRAP1) association p(HGNC:BRAF)

It is worth noting that TRAP1 regulation on BRAF is conserved in human colorectal carcinomas, with the two proteins being frequently coexpressed. PubMed:25239454

p(HGNC:TGFBRAP1) association p(HGNC:BRAF)

This study reports that BRAF cytoprotective signaling involves TRAP1-dependent inhibition of the mitochondrial apoptotic pathway. PubMed:26084290

bp(GOBP:"cell cycle") association p(HGNC:BRAF)

The HSP90 chaperone TRAP1 is translational regulator of BRAF synthesis/ubiquitination, since BRAF down-regulation, ERK signaling inhibition and delay of cell cycle progression occur upon TRAP1 silencing/inhibition. Since TRAP1 is upregulated in human colorectal carcinomas (CRCs) and involved in protection from apoptosis and as human BRAF-driven CRCs are poorly responsive to anticancer therapies, the relationship between TRAP1 regulation of mitochondrial apoptotic pathway and BRAF antiapoptotic signaling has been further evaluated. PubMed:26084290

p(HGNC:HSP90AB1) association p(HGNC:BRAF)

The HSP90 chaperone TRAP1 is translational regulator of BRAF synthesis/ubiquitination, since BRAF down-regulation, ERK signaling inhibition and delay of cell cycle progression occur upon TRAP1 silencing/inhibition. Since TRAP1 is upregulated in human colorectal carcinomas (CRCs) and involved in protection from apoptosis and as human BRAF-driven CRCs are poorly responsive to anticancer therapies, the relationship between TRAP1 regulation of mitochondrial apoptotic pathway and BRAF antiapoptotic signaling has been further evaluated. PubMed:26084290

path(MESHD:Neoplasms) association p(HGNC:BRAF)

Here, the similarities but also the differential effects of RAS and BRAF oncogenic signalling are examined and further implications in personalized cancer diagnosis and therapy are discussed. PubMed:25361007

Out-Edges 101

act(p(HGNC:BRAF), ma(kin)) directlyIncreases act(p(HGNC:MAP2K2), ma(kin))

124 However, Ras-mediated recruitment of C-Raf to the cell membrane and Src activation are not the only steps involved in the activation of C-Raf. A-Raf, which is structurally similar to C-Raf, is activated in a similar manner; however, the pertinent structural and activational aspects of B-Raf differ from those of A-Raf and C-Raf. Although the structural domains and phosphorylation sites of Raf proteins differ, the greater degree of phosphorylated amino acids in B-Raf confers a 15- to 20- fold higher level of kinase activity in the basal state than either A-Raf or C-Raf, and B-Raf is therefore a much more robust activator of ERK phosphorylation.85,144,145 The differential splicing of B-raf may also account for the distinct kinase activity of the protein. In addition, the structures of several B-Raf mutants mimic the conformational changes unique to phosphorylated wild-type B-Raf, which may explain the ability of B-Raf mutants to activate ERK in the absence of stimulation. Other interactions. In addition to phosphorylation events, the activation status of C-Raf is regulated by protein-protein and protein-lipid interactions. As shown in Figure 2, C-Raf interacts with a diverse array of scaffolding proteins (kinase suppressor of Ras and MEK partner-1), adaptor proteins (Bcl-2-associated athanogene-1), chaperone proteins (Hsp90 and Hsp70), substrates (retinoblastoma protein [Rb]), lipids (phosphatidic acid, cholesterol-rich caveolae, and cytosolic lipid rafts), and cellular constituents, many of which, in turn, modulate its kinase activity.95 Activation of Downstream Effectors by Raf Activated Raf principally propagates signaling by phosphorylating the two dual-specificity MAPKKs, MEK1 and MEK2 (also referred to as MKK1 and MKK2; Figs 1 and 2). 75 The Raf isoforms are the best characterized MEK1 and MEK2 activators, and all Raf isoforms activate MEK1, whereas only B-Raf and C-Raf activate MEK2. PubMed:16170185

Annotations
Experimental Factor Ontology (EFO)
HeLa cell
NCBI Taxonomy Ids
9606
Uberon
lung
Cell Ontology (CL)
macrophage
MeSH
Extracellular Matrix
Disease Ontology (DO)
breast cancer
MeSH
Sputum
MeSH
Head and Neck Neoplasms

act(p(HGNC:BRAF), ma(kin)) directlyIncreases act(p(HGNC:MAP2K2), ma(kin))

Collectively, these results indicate that IGFBP7 inhibits BRAF-MEK-ERK signaling by inducing RKIP, which prevents BRAF from phosphorylating MEK. PubMed:18267069

Annotations
Experimental Factor Ontology (EFO)
SK-N-MC cell
NCBI Taxonomy Ids
9606
Uberon
cardiovascular system
Cell Ontology (CL)
melanocyte
MeSH
Cell Nucleus
Disease Ontology (DO)
breast cancer
MeSH
Sputum
MeSH
Head and Neck Neoplasms

act(p(HGNC:BRAF), ma(kin)) increases act(p(HGNC:ELK1), ma(tscript))

Modified assertion PubMed:11283246

Annotations
Experimental Factor Ontology (EFO)
Dede cell
NCBI Taxonomy Ids
9606
Uberon
skeletal muscle tissue
Cell Ontology (CL)
endothelial cell
MeSH
Cell Membrane
Disease Ontology (DO)
leukemia

act(p(HGNC:BRAF), ma(kin)) increases act(p(HGNC:MAPK3), ma(kin))

In addition, introduction of B-Raf enhances and sustains integrin-mediated activation of ERK in wild-type primary fibroblasts PubMed:10976102

Annotations
Experimental Factor Ontology (EFO)
THP-1 cell
NCBI Taxonomy Ids
9606
Uberon
lung
Cell Ontology (CL)
fibroblast
MeSH
Cytoplasm
Disease Ontology (DO)
ovarian cancer

act(p(HGNC:BRAF), ma(kin)) increases act(p(HGNC:MAPK3), ma(kin))

siRNA-mediated depletion of B-Raf reduced cell proliferation by up to 65% through the inhibition of ERK1/2 activation, irrespective of the mutational status of B-Raf. PubMed:16452469

Annotations
Experimental Factor Ontology (EFO)
PC-3 cell
NCBI Taxonomy Ids
9606
Uberon
zone of skin
Cell Ontology (CL)
neuron
MeSH
Cytoplasm
Disease Ontology (DO)
non-small cell lung carcinoma
MeSH
Sputum
MeSH
Head and Neck Neoplasms

act(p(HGNC:BRAF), ma(kin)) directlyIncreases act(p(HGNC:MAP2K1), ma(kin))

hKSR-2 selectively inhibited the Cot-mediated activation of MEK by 60%. In contrast, hKSR-2 up-regulated the Rafmediated MEK activation by up to 70%. PubMed:12975377

Annotations
Experimental Factor Ontology (EFO)
A-431 cell
NCBI Taxonomy Ids
9606
Uberon
epithelium
Cell Ontology (CL)
monocyte
MeSH
Cell Nucleus
Disease Ontology (DO)
leukemia

act(p(HGNC:BRAF), ma(kin)) directlyIncreases act(p(HGNC:MAP2K1), ma(kin))

124 However, Ras-mediated recruitment of C-Raf to the cell membrane and Src activation are not the only steps involved in the activation of C-Raf. A-Raf, which is structurally similar to C-Raf, is activated in a similar manner; however, the pertinent structural and activational aspects of B-Raf differ from those of A-Raf and C-Raf. Although the structural domains and phosphorylation sites of Raf proteins differ, the greater degree of phosphorylated amino acids in B-Raf confers a 15- to 20- fold higher level of kinase activity in the basal state than either A-Raf or C-Raf, and B-Raf is therefore a much more robust activator of ERK phosphorylation.85,144,145 The differential splicing of B-raf may also account for the distinct kinase activity of the protein. In addition, the structures of several B-Raf mutants mimic the conformational changes unique to phosphorylated wild-type B-Raf, which may explain the ability of B-Raf mutants to activate ERK in the absence of stimulation. Other interactions. In addition to phosphorylation events, the activation status of C-Raf is regulated by protein-protein and protein-lipid interactions. As shown in Figure 2, C-Raf interacts with a diverse array of scaffolding proteins (kinase suppressor of Ras and MEK partner-1), adaptor proteins (Bcl-2-associated athanogene-1), chaperone proteins (Hsp90 and Hsp70), substrates (retinoblastoma protein [Rb]), lipids (phosphatidic acid, cholesterol-rich caveolae, and cytosolic lipid rafts), and cellular constituents, many of which, in turn, modulate its kinase activity.95 Activation of Downstream Effectors by Raf Activated Raf principally propagates signaling by phosphorylating the two dual-specificity MAPKKs, MEK1 and MEK2 (also referred to as MKK1 and MKK2; Figs 1 and 2). 75 The Raf isoforms are the best characterized MEK1 and MEK2 activators, and all Raf isoforms activate MEK1, whereas only B-Raf and C-Raf activate MEK2. PubMed:16170185

Annotations
Experimental Factor Ontology (EFO)
HeLa cell
NCBI Taxonomy Ids
9606
Uberon
lung
Cell Ontology (CL)
macrophage
MeSH
Extracellular Matrix
Disease Ontology (DO)
breast cancer
MeSH
Sputum
MeSH
Head and Neck Neoplasms

act(p(HGNC:BRAF), ma(kin)) directlyIncreases act(p(HGNC:MAP2K1), ma(kin))

Collectively, these results indicate that IGFBP7 inhibits BRAF-MEK-ERK signaling by inducing RKIP, which prevents BRAF from phosphorylating MEK. PubMed:18267069

Annotations
Experimental Factor Ontology (EFO)
SK-N-MC cell
NCBI Taxonomy Ids
9606
Uberon
cardiovascular system
Cell Ontology (CL)
melanocyte
MeSH
Cell Nucleus
Disease Ontology (DO)
breast cancer
MeSH
Sputum
MeSH
Head and Neck Neoplasms

act(p(HGNC:BRAF), ma(kin)) increases act(p(SFAM:"MAPK Erk1/2 Family"), ma(kin))

Modified assertion PubMed:11283246

Annotations
Experimental Factor Ontology (EFO)
Dede cell
NCBI Taxonomy Ids
9606
Uberon
skeletal muscle tissue
Cell Ontology (CL)
endothelial cell
MeSH
Cell Membrane
Disease Ontology (DO)
leukemia

act(p(HGNC:BRAF), ma(kin)) increases bp(GOBP:"cell proliferation")

siRNA-mediated depletion of B-Raf reduced cell proliferation by up to 65% through the inhibition of ERK1/2 activation, irrespective of the mutational status of B-Raf. PubMed:16452469

Annotations
Experimental Factor Ontology (EFO)
PC-3 cell
NCBI Taxonomy Ids
9606
Uberon
zone of skin
Cell Ontology (CL)
neuron
MeSH
Cytoplasm
Disease Ontology (DO)
non-small cell lung carcinoma
MeSH
Sputum
MeSH
Head and Neck Neoplasms

act(p(HGNC:BRAF), ma(kin)) increases act(p(HGNC:MAPK1), ma(kin))

In addition, introduction of B-Raf enhances and sustains integrin-mediated activation of ERK in wild-type primary fibroblasts PubMed:10976102

Annotations
Experimental Factor Ontology (EFO)
THP-1 cell
NCBI Taxonomy Ids
9606
Uberon
lung
Cell Ontology (CL)
fibroblast
MeSH
Cytoplasm
Disease Ontology (DO)
ovarian cancer

act(p(HGNC:BRAF), ma(kin)) increases act(p(HGNC:MAPK1), ma(kin))

elevated cAMP levels lead to the activation of B-Raf and hence to ERK activation PubMed:14641023

Annotations
Experimental Factor Ontology (EFO)
SW480 cell
NCBI Taxonomy Ids
9606
Uberon
peritoneum
Cell Ontology (CL)
fat cell
MeSH
Cell Membrane
Disease Ontology (DO)
lung cancer

act(p(HGNC:BRAF), ma(kin)) increases act(p(HGNC:MAPK1), ma(kin))

siRNA-mediated depletion of B-Raf reduced cell proliferation by up to 65% through the inhibition of ERK1/2 activation, irrespective of the mutational status of B-Raf. PubMed:16452469

Annotations
Experimental Factor Ontology (EFO)
PC-3 cell
NCBI Taxonomy Ids
9606
Uberon
zone of skin
Cell Ontology (CL)
neuron
MeSH
Cytoplasm
Disease Ontology (DO)
non-small cell lung carcinoma
MeSH
Sputum
MeSH
Head and Neck Neoplasms

act(p(HGNC:BRAF), ma(kin)) directlyIncreases act(p(SFAM:"MEK1/2 Family"), ma(kin))

From CST pathway map for GPCR Signaling to ERK. PubMed:16890451

Annotations
Experimental Factor Ontology (EFO)
293T/17 cell
NCBI Taxonomy Ids
9606
Uberon
liver
Cell Ontology (CL)
fat cell
MeSH
Cell Membrane
Disease Ontology (DO)
liver cancer
MeSH
Sputum
MeSH
Head and Neck Neoplasms

act(p(HGNC:BRAF), ma(kin)) directlyIncreases act(p(HGNC:MAP2K1), ma(kin))

The Raf isoforms are the best characterized MEK1 and MEK2 activators, and all Raf isoforms activate MEK1, whereas only B-Raf and C-Raf activate MEK2. MEK1 and MEK2 contain a proline-rich sequence that enables recognition and activation by Raf.125,146-153. PubMed:16170185

Annotations
Experimental Factor Ontology (EFO)
U-937 cell
NCBI Taxonomy Ids
9606
Uberon
cardiovascular system endothelium
Cell Ontology (CL)
fibroblast
MeSH
Cytoplasm
Disease Ontology (DO)
cancer
MeSH
Muscle, Smooth, Vascular

act(p(HGNC:BRAF), ma(kin)) directlyIncreases act(p(HGNC:MAP2K2), ma(kin))

The Raf isoforms are the best characterized MEK1 and MEK2 activators, and all Raf isoforms activate MEK1, whereas only B-Raf and C-Raf activate MEK2. MEK1 and MEK2 contain a proline-rich sequence that enables recognition and activation by Raf.125,146-153. PubMed:16170185

Annotations
Experimental Factor Ontology (EFO)
U-937 cell
NCBI Taxonomy Ids
9606
Uberon
cardiovascular system endothelium
Cell Ontology (CL)
fibroblast
MeSH
Cytoplasm
Disease Ontology (DO)
cancer
MeSH
Muscle, Smooth, Vascular

act(p(HGNC:BRAF), ma(kin)) positiveCorrelation path(MESHD:"Ovarian Neoplasms")

Somatic B-raf mutations were demonstrated in 60% to 70% of malignant melanomas and in moderate to high rates in carcinomas of the colon, ovary, and thyroid (papillary), implicating activating oncogenic B-raf mutations as critical promoters of these malignancies.9,14-17 PubMed:16170185

Annotations
Experimental Factor Ontology (EFO)
U-937 cell
NCBI Taxonomy Ids
9606
Uberon
cardiovascular system endothelium
Cell Ontology (CL)
fibroblast
MeSH
Cytoplasm
Disease Ontology (DO)
cancer
MeSH
Muscle, Smooth, Vascular

act(p(HGNC:BRAF), ma(kin)) positiveCorrelation path(MESHD:Melanoma)

Somatic B-raf mutations were demonstrated in 60% to 70% of malignant melanomas and in moderate to high rates in carcinomas of the colon, ovary, and thyroid (papillary), implicating activating oncogenic B-raf mutations as critical promoters of these malignancies.9,14-17 PubMed:16170185

Annotations
Experimental Factor Ontology (EFO)
U-937 cell
NCBI Taxonomy Ids
9606
Uberon
cardiovascular system endothelium
Cell Ontology (CL)
fibroblast
MeSH
Cytoplasm
Disease Ontology (DO)
cancer
MeSH
Muscle, Smooth, Vascular

act(p(HGNC:BRAF), ma(kin)) increases p(SFAM:"MAPK Erk1/2 Family", pmod(Ph))

Additional support for the diverse functionality of Raf family members is provided by the disparate responses of B-Raf and C-Raf to identical stimuli, as well as the distinct messages that each isoform relays downstream to Rap1, which is a small GTPase that functions as both an activator and repressor of Raf.115 Rap1-mediated stimulation of B-Raf by cyclic adenosine monophosphate (cAMP) phosphorylates ERK, whereas stimulation of C-Raf inhibits ERK phosphorylation.115 PubMed:16170185

Annotations
Experimental Factor Ontology (EFO)
U-937 cell
NCBI Taxonomy Ids
9606
Uberon
cardiovascular system endothelium
Cell Ontology (CL)
fibroblast
MeSH
Cell Membrane
Disease Ontology (DO)
cancer
MeSH
Muscle, Smooth, Vascular

act(p(HGNC:BRAF), ma(kin)) positiveCorrelation path(MESHD:"Thyroid Neoplasms")

Somatic B-raf mutations were demonstrated in 60% to 70% of malignant melanomas and in moderate to high rates in carcinomas of the colon, ovary, and thyroid (papillary), implicating activating oncogenic B-raf mutations as critical promoters of these malignancies.9,14-17 PubMed:16170185

Annotations
Experimental Factor Ontology (EFO)
U-937 cell
NCBI Taxonomy Ids
9606
Uberon
cardiovascular system endothelium
Cell Ontology (CL)
fibroblast
MeSH
Cytoplasm
Disease Ontology (DO)
cancer
MeSH
Muscle, Smooth, Vascular

act(p(HGNC:BRAF), ma(kin)) positiveCorrelation path(MESHD:"Colorectal Neoplasms")

Somatic B-raf mutations were demonstrated in 60% to 70% of malignant melanomas and in moderate to high rates in carcinomas of the colon, ovary, and thyroid (papillary), implicating activating oncogenic B-raf mutations as critical promoters of these malignancies.9,14-17 PubMed:16170185

Annotations
Experimental Factor Ontology (EFO)
U-937 cell
NCBI Taxonomy Ids
9606
Uberon
cardiovascular system endothelium
Cell Ontology (CL)
fibroblast
MeSH
Cytoplasm
Disease Ontology (DO)
cancer
MeSH
Muscle, Smooth, Vascular

act(p(HGNC:BRAF), ma(kin)) increases act(p(SFAM:"MEK1/2 Family"), ma(kin))

"ERK activation was monitored indirectly by measuring the rate of transcription induced by one of its downstream nuclear targets, Elk1....This activity was dependent on ERK activation, since it was completely blocked by the MEK inhibitor PD98059...Thus, in UT7-Mpl cells, Rap1, but not Ras, can couple B-Raf to ERK activation." Other:11283246

act(p(HGNC:BRAF), ma(kin)) directlyIncreases act(p(HGNC:MAP2K1), ma(kin))

Collectively, these results indicate that IGFBP7 inhibits BRAF-MEK-ERK signaling by inducing RKIP, which prevents BRAF from phosphorylating MEK. PubMed:18267069

Appears in Networks:

act(p(HGNC:BRAF), ma(kin)) directlyIncreases act(p(HGNC:MAP2K1), ma(kin))

124 However, Ras-mediated recruitment of C-Raf to the cell membrane and Src activation are not the only steps involved in the activation of C-Raf. A-Raf, which is structurally similar to C-Raf, is activated in a similar manner; however, the pertinent structural and activational aspects of B-Raf differ from those of A-Raf and C-Raf. Although the structural domains and phosphorylation sites of Raf proteins differ, the greater degree of phosphorylated amino acids in B-Raf confers a 15- to 20- fold higher level of kinase activity in the basal state than either A-Raf or C-Raf, and B-Raf is therefore a much more robust activator of ERK phosphorylation.85,144,145 The differential splicing of B-raf may also account for the distinct kinase activity of the protein. In addition, the structures of several B-Raf mutants mimic the conformational changes unique to phosphorylated wild-type B-Raf, which may explain the ability of B-Raf mutants to activate ERK in the absence of stimulation. Other interactions. In addition to phosphorylation events, the activation status of C-Raf is regulated by protein-protein and protein-lipid interactions. As shown in Figure 2, C-Raf interacts with a diverse array of scaffolding proteins (kinase suppressor of Ras and MEK partner-1), adaptor proteins (Bcl-2-associated athanogene-1), chaperone proteins (Hsp90 and Hsp70), substrates (retinoblastoma protein [Rb]), lipids (phosphatidic acid, cholesterol-rich caveolae, and cytosolic lipid rafts), and cellular constituents, many of which, in turn, modulate its kinase activity.95 Activation of Downstream Effectors by Raf Activated Raf principally propagates signaling by phosphorylating the two dual-specificity MAPKKs, MEK1 and MEK2 (also referred to as MKK1 and MKK2; Figs 1 and 2). 75 The Raf isoforms are the best characterized MEK1 and MEK2 activators, and all Raf isoforms activate MEK1, whereas only B-Raf and C-Raf activate MEK2. PubMed:16170185

Appears in Networks:

act(p(HGNC:BRAF), ma(kin)) directlyIncreases act(p(HGNC:MAP2K1), ma(kin))

hKSR-2 selectively inhibited the Cot-mediated activation of MEK by 60%. In contrast, hKSR-2 up-regulated the Rafmediated MEK activation by up to 70%. PubMed:12975377

Appears in Networks:

p(HGNC:BRAF) association p(HGNC:TRAP1)

This study shows that TRAP1 is involved in the regulation of BRAF synthesis/ubiquitination, without affecting its stability. PubMed:25239454

Annotations
Experimental Factor Ontology (EFO)
cell line
MeSH
Colorectal Neoplasms
MeSH
Breast Neoplasms
Evidence and Conclusion Ontology
RNAi
MeSH
Heterografts
NCBI Taxonomy Names
Homo sapiens

p(HGNC:BRAF) association p(HGNC:TRAP1)

It is worth noting that TRAP1 regulation on BRAF is conserved in human colorectal carcinomas, with the two proteins being frequently coexpressed. PubMed:25239454

Annotations
Experimental Factor Ontology (EFO)
cell line
MeSH
Colorectal Neoplasms
Evidence and Conclusion Ontology
RNAi
MeSH
Heterografts
NCBI Taxonomy Names
Homo sapiens

p(HGNC:BRAF) association p(HGNC:TGFBRAP1)

This study reports that BRAF cytoprotective signaling involves TRAP1-dependent inhibition of the mitochondrial apoptotic pathway. PubMed:26084290

Annotations
MeSH
Peroxisomes
Experimental Factor Ontology (EFO)
COLO205
MeSH
Colorectal Neoplasms
Evidence and Conclusion Ontology
combinatorial
MeSH
Blood Platelets
MeSH
Endothelium, Vascular
NCBI Taxonomy Names
Homo sapiens
NCBI Taxonomy Ids
10117

p(HGNC:BRAF) association bp(GOBP:"cell cycle")

The HSP90 chaperone TRAP1 is translational regulator of BRAF synthesis/ubiquitination, since BRAF down-regulation, ERK signaling inhibition and delay of cell cycle progression occur upon TRAP1 silencing/inhibition. Since TRAP1 is upregulated in human colorectal carcinomas (CRCs) and involved in protection from apoptosis and as human BRAF-driven CRCs are poorly responsive to anticancer therapies, the relationship between TRAP1 regulation of mitochondrial apoptotic pathway and BRAF antiapoptotic signaling has been further evaluated. PubMed:26084290

Annotations
MeSH
Peroxisomes
Experimental Factor Ontology (EFO)
COLO205
MeSH
Colorectal Neoplasms
Evidence and Conclusion Ontology
combinatorial
MeSH
Blood Platelets
MeSH
Endothelium, Vascular
NCBI Taxonomy Names
Homo sapiens
NCBI Taxonomy Ids
10117

p(HGNC:BRAF) association p(HGNC:HSP90AB1)

The HSP90 chaperone TRAP1 is translational regulator of BRAF synthesis/ubiquitination, since BRAF down-regulation, ERK signaling inhibition and delay of cell cycle progression occur upon TRAP1 silencing/inhibition. Since TRAP1 is upregulated in human colorectal carcinomas (CRCs) and involved in protection from apoptosis and as human BRAF-driven CRCs are poorly responsive to anticancer therapies, the relationship between TRAP1 regulation of mitochondrial apoptotic pathway and BRAF antiapoptotic signaling has been further evaluated. PubMed:26084290

Annotations
MeSH
Peroxisomes
Experimental Factor Ontology (EFO)
COLO205
MeSH
Colorectal Neoplasms
Evidence and Conclusion Ontology
combinatorial
MeSH
Blood Platelets
MeSH
Endothelium, Vascular
NCBI Taxonomy Names
Homo sapiens
NCBI Taxonomy Ids
10117

p(HGNC:BRAF) association p(HGNC:SIRT2)

SIRT2 loss also conferred resistance to BRAF and MEK inhibitors in BRAF mutant melanoma and KRAS mutant colon cancers, respectively. PubMed:24469059

Annotations
MeSH
Chromatin
Experimental Factor Ontology (EFO)
HCT116
MeSH
Melanoma
MeSH
Colorectal Neoplasms
Evidence and Conclusion Ontology
RNAi
MeSH
Serum
MeSH
Plasma
NCBI Taxonomy Names
Homo sapiens

p(HGNC:BRAF) biomarkerFor bp(MESHPP:"Drug Resistance")

Similarly, alterations of other members of the RAS-RAF-MAPK signaling pathway may also be such predictive markers, especially the BRAF mutation in colorectal cancer. PubMed:21942085

Annotations
MeSH
Chromatin
Experimental Factor Ontology (EFO)
HCT116
MeSH
Colorectal Neoplasms
Evidence and Conclusion Ontology
RNAi
MeSH
Tissues
NCBI Taxonomy Names
Homo sapiens

p(HGNC:BRAF) association bp(MESHPP:"Drug Resistance")

Other potentially useful biomarkers of resistance to EGFR-targeted therapy in the process of clinical validation include mutations in BRAF, PTEN loss and PI3KCA mutations, nuclear factor-kappa beta(NF-Κβ) pathway activity, and expression of alternative EGFR ligands. PubMed:20718710

Annotations
MeSH
Peroxisomes
Experimental Factor Ontology (EFO)
MDAMB435
MeSH
Neoplasms
Evidence and Conclusion Ontology
point mutation
MeSH
Heterografts
NCBI Taxonomy Names
Homo sapiens
NCBI Taxonomy Ids
10117

p(HGNC:BRAF) increases p(HGNC:TGFBRAP1, pmod(Ph, Ser))

It is worth noting that BRAF and TRAP1 interact and that the activation of BRAF signaling results in enhanced TRAP1 serine-phosphorylation, a condition associated with resistance to apoptosis. PubMed:26084290

Annotations
MeSH
Peroxisomes
Experimental Factor Ontology (EFO)
COLO205
MeSH
Colorectal Neoplasms
Evidence and Conclusion Ontology
combinatorial
MeSH
Blood Platelets
MeSH
Endothelium, Vascular
NCBI Taxonomy Names
Homo sapiens
NCBI Taxonomy Ids
10117

p(HGNC:BRAF) association path(MESHD:Neoplasms)

Here, the similarities but also the differential effects of RAS and BRAF oncogenic signalling are examined and further implications in personalized cancer diagnosis and therapy are discussed. PubMed:25361007

Annotations
MeSH
Chromatin
Experimental Factor Ontology (EFO)
SW620 cell
Experimental Factor Ontology (EFO)
WiDr cell
Experimental Factor Ontology (EFO)
HCT116
Experimental Factor Ontology (EFO)
HCT15
MeSH
Neoplasms
Evidence and Conclusion Ontology
immunohistochemistry
MeSH
Colon
NCBI Taxonomy Names
Homo sapiens
NCBI Taxonomy Ids
10117

deg(p(HGNC:BRAF)) decreases bp(GOBP:"cell migration")

Doxycyclin-inducible knockdown of endogenous B-Raf(V600E) decreases cellular motility and invasion in conventional and three-dimensional (3D) culture, whereas it promotes cell-cell contacts and induces various hallmarks of differentiated epithelia. Importantly, all these effects are recapitulated by B-Raf (PLX4720, vemurafenib, and dabrafenib) or MEK inhibitors (trametinib). PubMed:25381152

Annotations
NCBI Taxonomy Ids
9606
Experimental Factor Ontology (EFO)
LoVo
Disease Ontology (DO)
colorectal cancer
MeSH
Rectal Neoplasms

p(HGNC:BRAF) negativeCorrelation p(HGNC:KRAS)

Oncogenic activation of KRAS and BRAF is mutually exclusive and occurs in approximately 40% and 10% of all CRCs, respectively. PubMed:26299805

Annotations
NCBI Taxonomy Ids
9606
Experimental Factor Ontology (EFO)
HCT116
Disease Ontology (DO)
colorectal cancer
MeSH
Gastrointestinal Neoplasms

deg(p(HGNC:BRAF)) increases p(HGNC:CDX2)

Surprisingly, loss of B-Raf(V600E) in HT29 xenografts does not only stall tumor growth, but also induces glandular structures with marked expression of CDX2, a tumor-suppressor and master transcription factor of intestinal differentiation. PubMed:25381152

Annotations
NCBI Taxonomy Ids
9606
Experimental Factor Ontology (EFO)
HT-29
Disease Ontology (DO)
colorectal cancer
MeSH
Rectal Neoplasms

p(HGNC:BRAF) association path(MESHD:"Colorectal Neoplasms")

BRAF mutations are associated with aggressive, less-differentiated and therapy-resistant colorectal carcinoma. PubMed:25381152

Annotations
NCBI Taxonomy Ids
9606
Experimental Factor Ontology (EFO)
LoVo
Disease Ontology (DO)
colorectal cancer
MeSH
Rectal Neoplasms

p(HGNC:BRAF) association path(MESHD:Melanoma)

Signatures for BRAF oncogene have been revealed in melanoma. PubMed:22515520

Annotations
NCBI Taxonomy Ids
9606
Experimental Factor Ontology (EFO)
SW480
Disease Ontology (DO)
colorectal cancer
MeSH
Neoplasms

deg(p(HGNC:BRAF)) decreases path(MESHD:"Neoplasm Invasiveness")

Doxycyclin-inducible knockdown of endogenous B-Raf(V600E) decreases cellular motility and invasion in conventional and three-dimensional (3D) culture, whereas it promotes cell-cell contacts and induces various hallmarks of differentiated epithelia. Importantly, all these effects are recapitulated by B-Raf (PLX4720, vemurafenib, and dabrafenib) or MEK inhibitors (trametinib). PubMed:25381152

Annotations
NCBI Taxonomy Ids
9606
Experimental Factor Ontology (EFO)
LoVo
Disease Ontology (DO)
colorectal cancer
MeSH
Rectal Neoplasms

deg(p(HGNC:BRAF)) increases p(HGNC:CDX2)

Surprisingly, loss of B-Raf(V600E) in HT29 xenografts does not only stall tumor growth, but also induces glandular structures with marked expression of CDX2, a tumor-suppressor and master transcription factor of intestinal differentiation. PubMed:25381152

Annotations
MeSH
Microtubules
Experimental Factor Ontology (EFO)
HT-29
MeSH
Rectal Neoplasms
Evidence and Conclusion Ontology
immunohistochemistry
MeSH
Plasma
NCBI Taxonomy Names
Mus musculus
Disease Ontology (DO)
colorectal cancer
NCBI Taxonomy Ids
9606

p(HGNC:BRAF) association path(MESHD:Melanoma)

Signatures for BRAF oncogene have been revealed in melanoma. PubMed:22515520

Annotations
MeSH
Microtubules
Experimental Factor Ontology (EFO)
SW480
MeSH
Neoplasms
Evidence and Conclusion Ontology
immunohistochemistry
MeSH
Plasma
NCBI Taxonomy Names
Mus musculus
Disease Ontology (DO)
colorectal cancer
NCBI Taxonomy Ids
9606

deg(p(HGNC:BRAF)) decreases path(MESHD:"Neoplasm Invasiveness")

Doxycyclin-inducible knockdown of endogenous B-Raf(V600E) decreases cellular motility and invasion in conventional and three-dimensional (3D) culture, whereas it promotes cell-cell contacts and induces various hallmarks of differentiated epithelia. Importantly, all these effects are recapitulated by B-Raf (PLX4720, vemurafenib, and dabrafenib) or MEK inhibitors (trametinib). PubMed:25381152

Annotations
MeSH
Microtubules
Experimental Factor Ontology (EFO)
SW480
MeSH
Rectal Neoplasms
Evidence and Conclusion Ontology
immunohistochemistry
MeSH
Plasma
NCBI Taxonomy Names
Mus musculus
Disease Ontology (DO)
colorectal cancer
NCBI Taxonomy Ids
9606

deg(p(HGNC:BRAF)) decreases bp(GOBP:"cell migration")

Doxycyclin-inducible knockdown of endogenous B-Raf(V600E) decreases cellular motility and invasion in conventional and three-dimensional (3D) culture, whereas it promotes cell-cell contacts and induces various hallmarks of differentiated epithelia. Importantly, all these effects are recapitulated by B-Raf (PLX4720, vemurafenib, and dabrafenib) or MEK inhibitors (trametinib). PubMed:25381152

Annotations
MeSH
Microtubules
Experimental Factor Ontology (EFO)
SW480
MeSH
Rectal Neoplasms
Evidence and Conclusion Ontology
immunohistochemistry
MeSH
Plasma
NCBI Taxonomy Names
Mus musculus
Disease Ontology (DO)
colorectal cancer
NCBI Taxonomy Ids
9606

p(HGNC:BRAF) association path(MESHD:"Colorectal Neoplasms")

BRAF mutations are associated with aggressive, less-differentiated and therapy-resistant colorectal carcinoma. PubMed:25381152

Annotations
MeSH
Microtubules
Experimental Factor Ontology (EFO)
SW480
MeSH
Rectal Neoplasms
Evidence and Conclusion Ontology
immunohistochemistry
MeSH
Plasma
NCBI Taxonomy Names
Mus musculus
Disease Ontology (DO)
colorectal cancer
NCBI Taxonomy Ids
9606

p(HGNC:BRAF) negativeCorrelation p(HGNC:KRAS)

Oncogenic activation of KRAS and BRAF is mutually exclusive and occurs in approximately 40% and 10% of all CRCs, respectively. PubMed:26299805

Annotations
MeSH
Microtubules
Experimental Factor Ontology (EFO)
HCT116
MeSH
Gastrointestinal Neoplasms
Evidence and Conclusion Ontology
immunohistochemistry
MeSH
Plasma
NCBI Taxonomy Names
Mus musculus
Disease Ontology (DO)
colorectal cancer
NCBI Taxonomy Ids
9606

deg(p(HGNC:BRAF)) decreases bp(GOBP:"cell migration")

Doxycyclin-inducible knockdown of endogenous B-Raf(V600E) decreases cellular motility and invasion in conventional and three-dimensional (3D) culture, whereas it promotes cell-cell contacts and induces various hallmarks of differentiated epithelia. Importantly, all these effects are recapitulated by B-Raf (PLX4720, vemurafenib, and dabrafenib) or MEK inhibitors (trametinib). PubMed:25381152

p(HGNC:BRAF) negativeCorrelation p(HGNC:KRAS)

Oncogenic activation of KRAS and BRAF is mutually exclusive and occurs in approximately 40% and 10% of all CRCs, respectively. PubMed:26299805

deg(p(HGNC:BRAF)) increases p(HGNC:CDX2)

Surprisingly, loss of B-Raf(V600E) in HT29 xenografts does not only stall tumor growth, but also induces glandular structures with marked expression of CDX2, a tumor-suppressor and master transcription factor of intestinal differentiation. PubMed:25381152

p(HGNC:BRAF) association path(MESHD:"Colorectal Neoplasms")

BRAF mutations are associated with aggressive, less-differentiated and therapy-resistant colorectal carcinoma. PubMed:25381152

deg(p(HGNC:BRAF)) decreases path(MESHD:"Neoplasm Invasiveness")

Doxycyclin-inducible knockdown of endogenous B-Raf(V600E) decreases cellular motility and invasion in conventional and three-dimensional (3D) culture, whereas it promotes cell-cell contacts and induces various hallmarks of differentiated epithelia. Importantly, all these effects are recapitulated by B-Raf (PLX4720, vemurafenib, and dabrafenib) or MEK inhibitors (trametinib). PubMed:25381152

deg(p(HGNC:BRAF)) decreases path(MESHD:"Neoplasm Invasiveness")

Doxycyclin-inducible knockdown of endogenous B-Raf(V600E) decreases cellular motility and invasion in conventional and three-dimensional (3D) culture, whereas it promotes cell-cell contacts and induces various hallmarks of differentiated epithelia. Importantly, all these effects are recapitulated by B-Raf (PLX4720, vemurafenib, and dabrafenib) or MEK inhibitors (trametinib). PubMed:25381152

Annotations
Experimental Factor Ontology (EFO)
LoVo cell
Experimental Factor Ontology (EFO)
LOVO cell
MeSH
Intracellular Space
MeSH
Rectal Neoplasms
MeSH
Mucus
NCBI Taxonomy Names
Crataegus azarolus
Disease Ontology (DO)
colorectal cancer
Uberon
intestinal epithelium
Cell Ontology (CL)
stem cell
NCBI Taxonomy Ids
9606

p(HGNC:BRAF) association path(MESHD:Neoplasms)

Here, the similarities but also the differential effects of RAS and BRAF oncogenic signalling are examined and further implications in personalized cancer diagnosis and therapy are discussed. PubMed:25361007

Annotations
Experimental Factor Ontology (EFO)
COLO205
MeSH
Chromatin
MeSH
Neoplasms
Evidence and Conclusion Ontology
western blot
MeSH
Colon
NCBI Taxonomy Names
Homo sapiens
Disease Ontology (DO)
colorectal cancer
Uberon
intestinal epithelium
Cell Ontology (CL)
stem cell
NCBI Taxonomy Ids
10090

deg(p(HGNC:BRAF)) causesNoChange bp(MESHPP:"Absorption, Radiation")

DLD-1 and HT-29 cells were used for 3D-colony formation, invasion and proliferation assays and Western blotting. β1 integrin, focal adhesion kinase and EGFR were inhibited by AIIB2, TAE226 and Cetuximab, respectively. KRAS and BRAF knockdown were accomplished using small-interfering RNA technology. Single doses of X-rays ranged from 2Gy to 6Gy and 5-fluorouracil (5-FU) concentration was 10μM. RESULTS: Neither β1-integrin/EGFR inhibition nor KRAS or BRAF depletion nor 5-FU significantly modified CRC cell radiosensitivity. Cetuximab, AIIB2 and Cetuximab/AIIB2 differentially modulated MAPK, JNK and AKT phosphorylation. AIIB2 and TAE226 significantly decreased cell invasion. PubMed:26096850

Annotations
Experimental Factor Ontology (EFO)
HT-29
Experimental Factor Ontology (EFO)
DLD1
MeSH
Intracellular Space
MeSH
Gastrointestinal Neoplasms
MeSH
Mucus
NCBI Taxonomy Names
Crataegus azarolus
Disease Ontology (DO)
colorectal cancer
Uberon
intestinal epithelium
Cell Ontology (CL)
stem cell
NCBI Taxonomy Ids
9606

p(HGNC:BRAF) association p(HGNC:TRAP1)

This study shows that TRAP1 is involved in the regulation of BRAF synthesis/ubiquitination, without affecting its stability. PubMed:25239454

Annotations
Experimental Factor Ontology (EFO)
COLO205
MeSH
Chromatin
MeSH
Colorectal Neoplasms
MeSH
Breast Neoplasms
Evidence and Conclusion Ontology
western blot
MeSH
Colon
NCBI Taxonomy Names
Homo sapiens
Disease Ontology (DO)
colorectal cancer
Uberon
intestinal epithelium
Cell Ontology (CL)
stem cell
NCBI Taxonomy Ids
10090

p(HGNC:BRAF) association p(HGNC:TRAP1)

It is worth noting that TRAP1 regulation on BRAF is conserved in human colorectal carcinomas, with the two proteins being frequently coexpressed. PubMed:25239454

Annotations
Experimental Factor Ontology (EFO)
COLO205
MeSH
Chromatin
MeSH
Colorectal Neoplasms
Evidence and Conclusion Ontology
western blot
MeSH
Colon
NCBI Taxonomy Names
Homo sapiens
Disease Ontology (DO)
colorectal cancer
Uberon
intestinal epithelium
Cell Ontology (CL)
stem cell
NCBI Taxonomy Ids
10090

p(HGNC:BRAF) association bp(GOBP:"cell cycle")

The HSP90 chaperone TRAP1 is translational regulator of BRAF synthesis/ubiquitination, since BRAF down-regulation, ERK signaling inhibition and delay of cell cycle progression occur upon TRAP1 silencing/inhibition. Since TRAP1 is upregulated in human colorectal carcinomas (CRCs) and involved in protection from apoptosis and as human BRAF-driven CRCs are poorly responsive to anticancer therapies, the relationship between TRAP1 regulation of mitochondrial apoptotic pathway and BRAF antiapoptotic signaling has been further evaluated. PubMed:26084290

Annotations
Experimental Factor Ontology (EFO)
HT-29
MeSH
Chromatin
MeSH
Colorectal Neoplasms
Evidence and Conclusion Ontology
RNAi
MeSH
Serum
MeSH
Colon
MeSH
Heterografts
NCBI Taxonomy Names
Homo sapiens
Disease Ontology (DO)
colorectal cancer
Uberon
intestinal epithelium
Cell Ontology (CL)
stem cell
NCBI Taxonomy Ids
10090

p(HGNC:BRAF) association bp(MESHPP:"Drug Resistance")

BRAF mutations are associated with aggressive, less-differentiated and therapy-resistant colorectal carcinoma. PubMed:25381152

Annotations
Experimental Factor Ontology (EFO)
LoVo cell
Experimental Factor Ontology (EFO)
LOVO cell
MeSH
Intracellular Space
MeSH
Rectal Neoplasms
MeSH
Mucus
NCBI Taxonomy Names
Crataegus azarolus
Disease Ontology (DO)
colorectal cancer
Uberon
intestinal epithelium
Cell Ontology (CL)
stem cell
NCBI Taxonomy Ids
9606

p(HGNC:BRAF) association bp(MESHPP:"Drug Resistance")

Other potentially useful biomarkers of resistance to EGFR-targeted therapy in the process of clinical validation include mutations in BRAF, PTEN loss and PI3KCA mutations, nuclear factor-kappa beta(NF-Κβ) pathway activity, and expression of alternative EGFR ligands. PubMed:20718710

Annotations
Experimental Factor Ontology (EFO)
HeLa cell
MeSH
Peroxisomes
MeSH
Neoplasms
Evidence and Conclusion Ontology
point mutation
MeSH
Colon
NCBI Taxonomy Names
Homo sapiens
Disease Ontology (DO)
colorectal cancer
Uberon
intestinal epithelium
Cell Ontology (CL)
stem cell
NCBI Taxonomy Ids
10090

p(HGNC:BRAF) biomarkerFor bp(MESHPP:"Drug Resistance")

Similarly, alterations of other members of the RAS-RAF-MAPK signaling pathway may also be such predictive markers, especially the BRAF mutation in colorectal cancer. PubMed:21942085

Annotations
Experimental Factor Ontology (EFO)
HCT116
MeSH
Peroxisomes
MeSH
Colorectal Neoplasms
Evidence and Conclusion Ontology
immunohistochemistry
Evidence and Conclusion Ontology
protein expression
MeSH
Colon
NCBI Taxonomy Names
Homo sapiens
Disease Ontology (DO)
colorectal cancer
Uberon
intestinal epithelium
Cell Ontology (CL)
stem cell
NCBI Taxonomy Ids
10090

p(HGNC:BRAF) association p(HGNC:TGFBRAP1)

This study reports that BRAF cytoprotective signaling involves TRAP1-dependent inhibition of the mitochondrial apoptotic pathway. PubMed:26084290

Annotations
Experimental Factor Ontology (EFO)
HT-29
MeSH
Chromatin
MeSH
Colorectal Neoplasms
Evidence and Conclusion Ontology
RNAi
MeSH
Serum
MeSH
Colon
MeSH
Heterografts
NCBI Taxonomy Names
Homo sapiens
Disease Ontology (DO)
colorectal cancer
Uberon
intestinal epithelium
Cell Ontology (CL)
stem cell
NCBI Taxonomy Ids
10090

p(HGNC:BRAF) increases p(HGNC:TGFBRAP1, pmod(Ph, Ser))

It is worth noting that BRAF and TRAP1 interact and that the activation of BRAF signaling results in enhanced TRAP1 serine-phosphorylation, a condition associated with resistance to apoptosis. PubMed:26084290

Annotations
Experimental Factor Ontology (EFO)
HT-29
MeSH
Chromatin
MeSH
Colorectal Neoplasms
Evidence and Conclusion Ontology
RNAi
MeSH
Serum
MeSH
Colon
MeSH
Heterografts
NCBI Taxonomy Names
Homo sapiens
Disease Ontology (DO)
colorectal cancer
Uberon
intestinal epithelium
Cell Ontology (CL)
stem cell
NCBI Taxonomy Ids
10090

p(HGNC:BRAF) decreases p(HGNC:TGFBRAP1, pmod(Ph, Ser))

Consistently, a BRAF dominant-negative mutant prevents TRAP1 serine phosphorylation and restores drug sensitivity in BRAFV600E CRC drug-resistant cells with high TRAP1 levels. PubMed:26084290

Annotations
Experimental Factor Ontology (EFO)
HT-29
MeSH
Chromatin
MeSH
Colorectal Neoplasms
Evidence and Conclusion Ontology
dominant_negative mutant
MeSH
Serum
MeSH
Colon
MeSH
Heterografts
NCBI Taxonomy Names
Homo sapiens
Disease Ontology (DO)
colorectal cancer
Uberon
intestinal epithelium
Cell Ontology (CL)
stem cell
NCBI Taxonomy Ids
10090

deg(p(HGNC:BRAF)) increases p(HGNC:CDX2)

Surprisingly, loss of B-Raf(V600E) in HT29 xenografts does not only stall tumor growth, but also induces glandular structures with marked expression of CDX2, a tumor-suppressor and master transcription factor of intestinal differentiation. PubMed:25381152

Annotations
Experimental Factor Ontology (EFO)
HT-29
MeSH
Intracellular Space
MeSH
Rectal Neoplasms
MeSH
Mucus
NCBI Taxonomy Names
Crataegus azarolus
Disease Ontology (DO)
colorectal cancer
Uberon
intestinal epithelium
Cell Ontology (CL)
stem cell
NCBI Taxonomy Ids
9606

p(HGNC:BRAF) association p(HGNC:SIRT2)

SIRT2 loss also conferred resistance to BRAF and MEK inhibitors in BRAF mutant melanoma and KRAS mutant colon cancers, respectively. PubMed:24469059

Annotations
Experimental Factor Ontology (EFO)
HT-29
MeSH
Chromatin
MeSH
Melanoma
MeSH
Colorectal Neoplasms
Evidence and Conclusion Ontology
RNAi
MeSH
Tissues
NCBI Taxonomy Names
Homo sapiens
Disease Ontology (DO)
colorectal cancer
Uberon
intestinal epithelium
Cell Ontology (CL)
stem cell
NCBI Taxonomy Ids
10090

p(HGNC:BRAF) decreases a(CHEBI:"epidermal growth factor receptor antagonist")

Specific genomic colorectal cancer alterations are increasingly linked to prognosis and/or response to specific anticancer agents. The identification of KRAS mutations as markers of resistance to epidermal growth factor receptor (EGFR) inhibitors has paved the way to the interrogation of numerous other markers of resistance to anti-EGFR therapy, such as NRAS, BRAF, and PI3KCA mutations. PubMed:24158971

Annotations
Experimental Factor Ontology (EFO)
HCT116
MeSH
Intracellular Space
MeSH
Rectal Neoplasms
MeSH
Mucus
NCBI Taxonomy Names
Crataegus azarolus
Disease Ontology (DO)
colorectal cancer
Uberon
intestinal epithelium
Cell Ontology (CL)
stem cell
NCBI Taxonomy Ids
9606

p(HGNC:BRAF) association path(MESHD:"Colorectal Neoplasms")

BRAF mutations are associated with aggressive, less-differentiated and therapy-resistant colorectal carcinoma. PubMed:25381152

Annotations
Experimental Factor Ontology (EFO)
LoVo cell
Experimental Factor Ontology (EFO)
LOVO cell
MeSH
Intracellular Space
MeSH
Rectal Neoplasms
MeSH
Mucus
NCBI Taxonomy Names
Crataegus azarolus
Disease Ontology (DO)
colorectal cancer
Uberon
intestinal epithelium
Cell Ontology (CL)
stem cell
NCBI Taxonomy Ids
9606

deg(p(HGNC:BRAF)) decreases bp(GOBP:"cell migration")

Doxycyclin-inducible knockdown of endogenous B-Raf(V600E) decreases cellular motility and invasion in conventional and three-dimensional (3D) culture, whereas it promotes cell-cell contacts and induces various hallmarks of differentiated epithelia. Importantly, all these effects are recapitulated by B-Raf (PLX4720, vemurafenib, and dabrafenib) or MEK inhibitors (trametinib). PubMed:25381152

Annotations
Experimental Factor Ontology (EFO)
LoVo cell
Experimental Factor Ontology (EFO)
LOVO cell
MeSH
Intracellular Space
MeSH
Rectal Neoplasms
MeSH
Mucus
NCBI Taxonomy Names
Crataegus azarolus
Disease Ontology (DO)
colorectal cancer
Uberon
intestinal epithelium
Cell Ontology (CL)
stem cell
NCBI Taxonomy Ids
9606

p(HGNC:BRAF) decreases a(SCHEM:Cetuximab)

Genetic events in additional nodes of the mitogen-activated protein kinase (MAPK)-phosphoinositide 3-kinase (PI3K) pathways that bypass EGFR signaling, such as BRAF or PIK3CA mutations or KRAS, ERBB2, or MET amplifications, also may confer resistance to cetuximab or panitumumab. PubMed:25993166

p(HGNC:BRAF) association p(HGNC:HSP90AB1)

The HSP90 chaperone TRAP1 is translational regulator of BRAF synthesis/ubiquitination, since BRAF down-regulation, ERK signaling inhibition and delay of cell cycle progression occur upon TRAP1 silencing/inhibition. Since TRAP1 is upregulated in human colorectal carcinomas (CRCs) and involved in protection from apoptosis and as human BRAF-driven CRCs are poorly responsive to anticancer therapies, the relationship between TRAP1 regulation of mitochondrial apoptotic pathway and BRAF antiapoptotic signaling has been further evaluated. PubMed:26084290

Annotations
Experimental Factor Ontology (EFO)
HT-29
MeSH
Chromatin
MeSH
Colorectal Neoplasms
Evidence and Conclusion Ontology
RNAi
MeSH
Serum
MeSH
Colon
MeSH
Heterografts
NCBI Taxonomy Names
Homo sapiens
Disease Ontology (DO)
colorectal cancer
Uberon
intestinal epithelium
Cell Ontology (CL)
stem cell
NCBI Taxonomy Ids
10090

p(HGNC:BRAF) association path(MESHD:Melanoma)

Signatures for BRAF oncogene have been revealed in melanoma. PubMed:22515520

Annotations
Experimental Factor Ontology (EFO)
SW480
MeSH
Intracellular Space
MeSH
Neoplasms
MeSH
Mucus
NCBI Taxonomy Names
Crataegus azarolus
Disease Ontology (DO)
colorectal cancer
Uberon
intestinal epithelium
Cell Ontology (CL)
stem cell
NCBI Taxonomy Ids
9606

p(HGNC:BRAF) negativeCorrelation p(HGNC:KRAS)

Oncogenic activation of KRAS and BRAF is mutually exclusive and occurs in approximately 40% and 10% of all CRCs, respectively. PubMed:26299805

p(HGNC:BRAF) association path(MESHD:Neoplasms)

Here, the similarities but also the differential effects of RAS and BRAF oncogenic signalling are examined and further implications in personalized cancer diagnosis and therapy are discussed. PubMed:25361007

deg(p(HGNC:BRAF)) causesNoChange bp(MESHPP:"Absorption, Radiation")

DLD-1 and HT-29 cells were used for 3D-colony formation, invasion and proliferation assays and Western blotting. β1 integrin, focal adhesion kinase and EGFR were inhibited by AIIB2, TAE226 and Cetuximab, respectively. KRAS and BRAF knockdown were accomplished using small-interfering RNA technology. Single doses of X-rays ranged from 2Gy to 6Gy and 5-fluorouracil (5-FU) concentration was 10μM. RESULTS: Neither β1-integrin/EGFR inhibition nor KRAS or BRAF depletion nor 5-FU significantly modified CRC cell radiosensitivity. Cetuximab, AIIB2 and Cetuximab/AIIB2 differentially modulated MAPK, JNK and AKT phosphorylation. AIIB2 and TAE226 significantly decreased cell invasion. PubMed:26096850

Annotations
Experimental Factor Ontology (EFO)
HT-29
Experimental Factor Ontology (EFO)
DLD1
Disease Ontology (DO)
colorectal cancer
NCBI Taxonomy Ids
9606

p(HGNC:BRAF) association p(HGNC:TRAP1)

This study shows that TRAP1 is involved in the regulation of BRAF synthesis/ubiquitination, without affecting its stability. PubMed:25239454

p(HGNC:BRAF) association p(HGNC:TRAP1)

It is worth noting that TRAP1 regulation on BRAF is conserved in human colorectal carcinomas, with the two proteins being frequently coexpressed. PubMed:25239454

p(HGNC:BRAF) association bp(GOBP:"cell cycle")

The HSP90 chaperone TRAP1 is translational regulator of BRAF synthesis/ubiquitination, since BRAF down-regulation, ERK signaling inhibition and delay of cell cycle progression occur upon TRAP1 silencing/inhibition. Since TRAP1 is upregulated in human colorectal carcinomas (CRCs) and involved in protection from apoptosis and as human BRAF-driven CRCs are poorly responsive to anticancer therapies, the relationship between TRAP1 regulation of mitochondrial apoptotic pathway and BRAF antiapoptotic signaling has been further evaluated. PubMed:26084290

p(HGNC:BRAF) association bp(MESHPP:"Drug Resistance")

BRAF mutations are associated with aggressive, less-differentiated and therapy-resistant colorectal carcinoma. PubMed:25381152

p(HGNC:BRAF) association bp(MESHPP:"Drug Resistance")

Other potentially useful biomarkers of resistance to EGFR-targeted therapy in the process of clinical validation include mutations in BRAF, PTEN loss and PI3KCA mutations, nuclear factor-kappa beta(NF-Κβ) pathway activity, and expression of alternative EGFR ligands. PubMed:20718710

p(HGNC:BRAF) biomarkerFor bp(MESHPP:"Drug Resistance")

Similarly, alterations of other members of the RAS-RAF-MAPK signaling pathway may also be such predictive markers, especially the BRAF mutation in colorectal cancer. PubMed:21942085

p(HGNC:BRAF) increases p(HGNC:TGFBRAP1, pmod(Ph, Ser))

It is worth noting that BRAF and TRAP1 interact and that the activation of BRAF signaling results in enhanced TRAP1 serine-phosphorylation, a condition associated with resistance to apoptosis. PubMed:26084290

p(HGNC:BRAF) decreases p(HGNC:TGFBRAP1, pmod(Ph, Ser))

Consistently, a BRAF dominant-negative mutant prevents TRAP1 serine phosphorylation and restores drug sensitivity in BRAFV600E CRC drug-resistant cells with high TRAP1 levels. PubMed:26084290

p(HGNC:BRAF) association p(HGNC:SIRT2)

SIRT2 loss also conferred resistance to BRAF and MEK inhibitors in BRAF mutant melanoma and KRAS mutant colon cancers, respectively. PubMed:24469059

p(HGNC:BRAF) decreases a(CHEBI:"epidermal growth factor receptor antagonist")

Specific genomic colorectal cancer alterations are increasingly linked to prognosis and/or response to specific anticancer agents. The identification of KRAS mutations as markers of resistance to epidermal growth factor receptor (EGFR) inhibitors has paved the way to the interrogation of numerous other markers of resistance to anti-EGFR therapy, such as NRAS, BRAF, and PI3KCA mutations. PubMed:24158971

p(HGNC:BRAF) decreases a(SCHEM:Cetuximab)

Genetic events in additional nodes of the mitogen-activated protein kinase (MAPK)-phosphoinositide 3-kinase (PI3K) pathways that bypass EGFR signaling, such as BRAF or PIK3CA mutations or KRAS, ERBB2, or MET amplifications, also may confer resistance to cetuximab or panitumumab. PubMed:25993166

Annotations
Disease Ontology (DO)
colorectal cancer
NCBI Taxonomy Ids
9606

p(HGNC:BRAF) association p(HGNC:TGFBRAP1)

This study reports that BRAF cytoprotective signaling involves TRAP1-dependent inhibition of the mitochondrial apoptotic pathway. PubMed:26084290

p(HGNC:BRAF) decreases a(MeSH:panitumumab)

Genetic events in additional nodes of the mitogen-activated protein kinase (MAPK)-phosphoinositide 3-kinase (PI3K) pathways that bypass EGFR signaling, such as BRAF or PIK3CA mutations or KRAS, ERBB2, or MET amplifications, also may confer resistance to cetuximab or panitumumab. PubMed:25993166

p(HGNC:BRAF) association p(HGNC:HSP90AB1)

The HSP90 chaperone TRAP1 is translational regulator of BRAF synthesis/ubiquitination, since BRAF down-regulation, ERK signaling inhibition and delay of cell cycle progression occur upon TRAP1 silencing/inhibition. Since TRAP1 is upregulated in human colorectal carcinomas (CRCs) and involved in protection from apoptosis and as human BRAF-driven CRCs are poorly responsive to anticancer therapies, the relationship between TRAP1 regulation of mitochondrial apoptotic pathway and BRAF antiapoptotic signaling has been further evaluated. PubMed:26084290

p(HGNC:BRAF) decreases a(MeSH:panitumumab)

Genetic events in additional nodes of the mitogen-activated protein kinase (MAPK)-phosphoinositide 3-kinase (PI3K) pathways that bypass EGFR signaling, such as BRAF or PIK3CA mutations or KRAS, ERBB2, or MET amplifications, also may confer resistance to cetuximab or panitumumab. PubMed:25993166

Annotations
Experimental Factor Ontology (EFO)
HCT 116 cell
MeSH
Intracellular Space
MeSH
Gastrointestinal Neoplasms
MeSH
Mucus
NCBI Taxonomy Names
Crataegus azarolus
Disease Ontology (DO)
colorectal cancer
Uberon
intestinal epithelium
Cell Ontology (CL)
stem cell
NCBI Taxonomy Ids
9606

p(HGNC:BRAF) decreases a(MeSH:Cetuximab)

Genetic events in additional nodes of the mitogen-activated protein kinase (MAPK)-phosphoinositide 3-kinase (PI3K) pathways that bypass EGFR signaling, such as BRAF or PIK3CA mutations or KRAS, ERBB2, or MET amplifications, also may confer resistance to cetuximab or panitumumab. PubMed:25993166

Annotations
Disease Ontology (DO)
colorectal cancer
NCBI Taxonomy Ids
9606

About

BEL Commons is developed and maintained in an academic capacity by Charles Tapley Hoyt and Daniel Domingo-Fernández at the Fraunhofer SCAI Department of Bioinformatics with support from the IMI project, AETIONOMY. It is built on top of the open source project, PyBEL. Please feel free to contact us here to give us feedback or report any issues.