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p(HGNC:SQSTM1)

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Entity

Name
SQSTM1
Namespace
hgnc
Namespace Version
20180906
Namespace URL
https://raw.githubusercontent.com/pharmacome/terminology/b46b65c3da259b6e86026514dfececab7c22a11b/external/hgnc-names.belns

Appears in Networks 9

The Biology of Proteostasis in Aging and Disease v1.0.0

Promoting the clearance of neurotoxic proteins in neurodegenerative disorders of ageing v1.0.0

Clearance of Amyloid Beta and Tau in Alzheimer’s Disease:from Mechanisms to Therapy v1.0.1

Oxidative stress in health and disease: The therapeutic potential of Nrf2 activation v1.0.0

Alzheimer’s disease and the autophagic-lysosomal system v1.0.0

The Ubiquitin–Proteasome System and the Autophagic–Lysosomal System in Alzheimer Disease v1.0.0

Autophagy and the ubiquitin-proteasome system: collaborators in neuroprotection v1.0.0

Pathological missorting of endogenous MAPT/Tau in neurons caused by failure of protein degradation systems v1.0.0

Pathological missorting of endogenous MAPT/Tau in neurons caused by failure of protein degradation systems v1.0.1

In-Edges 19

a(CHEBI:chloroquine) increases p(HGNC:SQSTM1) View Subject | View Object

Reduced levels of lipofuscin, LC3, and p62 have been observed in motor neurons of SOD1(G85R) mice (92). Treatment with the autophagy inhibitor chloroquine restored lipofuscin, LC3, and p62 levels in motor neurons, suggesting that mutant SOD1 causes hyperactive autophagy in mice (92). PubMed:25784053

Appears in Networks:
Annotations
Cell Ontology (CL)
motor neuron

p(HGNC:SOD1, var("p.Gly576Arg")) decreases p(HGNC:SQSTM1) View Subject | View Object

Reduced levels of lipofuscin, LC3, and p62 have been observed in motor neurons of SOD1(G85R) mice (92). Treatment with the autophagy inhibitor chloroquine restored lipofuscin, LC3, and p62 levels in motor neurons, suggesting that mutant SOD1 causes hyperactive autophagy in mice (92). PubMed:25784053

Appears in Networks:
Annotations
Cell Ontology (CL)
motor neuron

path(MESH:"Amyotrophic Lateral Sclerosis") association p(HGNC:SQSTM1) View Subject | View Object

ALS shares many causal genes with FTD, including SQSTM1, CHMP2B, TBK1 (which encodes tank-binding kinase 1), OPTN (which encodes optineurin) and other genes associated with deficits in ALN and mitophagy. PubMed:30116051

Appears in Networks:
Annotations
MeSH
Dopaminergic Neurons
MeSH
Amyotrophic Lateral Sclerosis

path(MESH:"Frontotemporal Dementia") association p(HGNC:SQSTM1) View Subject | View Object

However, in light of common risk genes such as SQSTM1 (which encodes p62) and chromosome 9 open reading frame 72 (C9ORF72), FTD is increasingly linked to ALS 82,83 . PubMed:30116051

Appears in Networks:
Annotations
MeSH
Dopaminergic Neurons
MeSH
Frontotemporal Dementia

a(CHEBI:"(-)-epigallocatechin 3-gallate") increases p(HGNC:SQSTM1) View Subject | View Object

Epigallocatechin-3-gallate enhances the clearance of ADrelevant phosphorylated tau species via increasing mRNA expression of autophagy adaptor proteins NDP52 and p62 (Chesser et al. 2016) PubMed:29626319

Appears in Networks:

a(PUBCHEM:135316034) increases p(HGNC:SQSTM1) View Subject | View Object

SQSTM1, induced 20-fold, encodes sequestosome-1, a participant in the autophagy pathway recently shown to be necessary to avoid premature senescence in human fibroblasts (Kang et al., 2011). PubMed:22020111

Appears in Networks:

a(CHEBI:"methylene blue") decreases p(HGNC:SQSTM1) View Subject | View Object

Methylene blue, a contrast agent that can reduce tau misfolding, has also been shown to induce macroautophagy, as indicated by elevated Beclin 1 and LC3-II levels and reduced tau and p62 levels in organotypic neuronal cultures and a mouse model of FTD [159] PubMed:29758300

Appears in Networks:

bp(GO:"lysosomal protein catabolic process") decreases p(HGNC:SQSTM1) View Subject | View Object

In APP transgenic mouse models of AD, undigested autophagy substrates including LC3-II, p62, and ubiquitinated proteins accumulate in neuronal AVs, establishing that autophagic protein turnover in lysosomes is impeded (Yang et al. 2011). PubMed:22908190

Appears in Networks:
Annotations
MeSH
Alzheimer Disease

bp(GO:"proteasomal protein catabolic process") association p(HGNC:SQSTM1) View Subject | View Object

For example, p62, an adaptor protein for autophagy, also influences proteasomal degradation, whereas VCP/p97 acting through p62 and ubiquitin regulates both the proteasome-dependent endoplasmic reticulum–associated degradation (ERAD) pathway and aspects of autophagosome maturation (Tresse et al. 2010). PubMed:22908190

Appears in Networks:

composite(a(MESH:Ubiquitin), p(HGNC:SQSTM1)) hasComponent p(HGNC:SQSTM1) View Subject | View Object

Appears in Networks:

a(GO:"Lewy body") association p(HGNC:SQSTM1) View Subject | View Object

p62 localizes to a variety of ubiquitin-positive neuropathological inclusions including Lewy bodies in Parkinson’s disease, neurofibrillary tangles in tauopathies, polyglutamine-expanded huntingtin aggregates in Huntington’s disease, and aggregates of mutant SOD1 in familial amyotrophic lateral sclerosis [85–87]. PubMed:18930136

Appears in Networks:
Annotations
MeSH
Parkinson Disease

a(GO:"neurofibrillary tangle") association p(HGNC:SQSTM1) View Subject | View Object

p62 localizes to a variety of ubiquitin-positive neuropathological inclusions including Lewy bodies in Parkinson’s disease, neurofibrillary tangles in tauopathies, polyglutamine-expanded huntingtin aggregates in Huntington’s disease, and aggregates of mutant SOD1 in familial amyotrophic lateral sclerosis [85–87]. PubMed:18930136

Appears in Networks:
Annotations
MeSH
Alzheimer Disease

bp(GO:"cellular response to stress") increases p(HGNC:SQSTM1) View Subject | View Object

Cellular stresses such as polyQ expression, proteasome impairment, oxidative stress, and increased misfolded protein burden activate transcription and translation of p62, suggesting that it functions broadly in stress situations [83,84] PubMed:18930136

Appears in Networks:

bp(GO:"protein K63-linked ubiquitination") increases act(p(HGNC:SQSTM1)) View Subject | View Object

Specifically, it is suggested that K63-linked polyubiquitin chains recruit p62 and HDAC6 providing a signal for autophagic degradation [92,93]. PubMed:18930136

Appears in Networks:

bp(GO:"response to oxidative stress") increases p(HGNC:SQSTM1) View Subject | View Object

Cellular stresses such as polyQ expression, proteasome impairment, oxidative stress, and increased misfolded protein burden activate transcription and translation of p62, suggesting that it functions broadly in stress situations [83,84] PubMed:18930136

Appears in Networks:

act(complex(GO:"proteasome complex")) decreases p(HGNC:SQSTM1) View Subject | View Object

Cellular stresses such as polyQ expression, proteasome impairment, oxidative stress, and increased misfolded protein burden activate transcription and translation of p62, suggesting that it functions broadly in stress situations [83,84] PubMed:18930136

Appears in Networks:

p(HGNC:SOD1, var("?")) association p(HGNC:SQSTM1) View Subject | View Object

p62 localizes to a variety of ubiquitin-positive neuropathological inclusions including Lewy bodies in Parkinson’s disease, neurofibrillary tangles in tauopathies, polyglutamine-expanded huntingtin aggregates in Huntington’s disease, and aggregates of mutant SOD1 in familial amyotrophic lateral sclerosis [85–87]. PubMed:18930136

Appears in Networks:
Annotations
MeSH
Amyotrophic Lateral Sclerosis

p(MESH:Proteins, pmod(HBP:misfolding)) increases p(HGNC:SQSTM1) View Subject | View Object

Cellular stresses such as polyQ expression, proteasome impairment, oxidative stress, and increased misfolded protein burden activate transcription and translation of p62, suggesting that it functions broadly in stress situations [83,84] PubMed:18930136

Appears in Networks:

p(HGNC:MAPT) increases p(HGNC:SQSTM1) View Subject | View Object

Compared with the MAPT-free dendrites of control neurons (Fig. S4A, 1.8±0.1), a substantial increase of SQSTM1 level (21.1±0.9) was observed in MAPT-containing dendrites upon wortmannin treatment (Fig. S4B). PubMed:30145931

Appears in Networks:
Annotations
MeSH
Dendrites

Out-Edges 21

p(HGNC:SQSTM1) association path(MESH:"Frontotemporal Dementia") View Subject | View Object

However, in light of common risk genes such as SQSTM1 (which encodes p62) and chromosome 9 open reading frame 72 (C9ORF72), FTD is increasingly linked to ALS 82,83 . PubMed:30116051

Appears in Networks:
Annotations
MeSH
Dopaminergic Neurons
MeSH
Frontotemporal Dementia

p(HGNC:SQSTM1) association path(MESH:"Amyotrophic Lateral Sclerosis") View Subject | View Object

ALS shares many causal genes with FTD, including SQSTM1, CHMP2B, TBK1 (which encodes tank-binding kinase 1), OPTN (which encodes optineurin) and other genes associated with deficits in ALN and mitophagy. PubMed:30116051

Appears in Networks:
Annotations
MeSH
Dopaminergic Neurons
MeSH
Amyotrophic Lateral Sclerosis

p(HGNC:SQSTM1) increases bp(GO:autophagy) View Subject | View Object

SQSTM1, induced 20-fold, encodes sequestosome-1, a participant in the autophagy pathway recently shown to be necessary to avoid premature senescence in human fibroblasts (Kang et al., 2011). PubMed:22020111

Appears in Networks:

p(HGNC:SQSTM1) decreases bp(GO:"stress-induced premature senescence") View Subject | View Object

SQSTM1, induced 20-fold, encodes sequestosome-1, a participant in the autophagy pathway recently shown to be necessary to avoid premature senescence in human fibroblasts (Kang et al., 2011). PubMed:22020111

Appears in Networks:
Annotations
MeSH
Fibroblasts

p(HGNC:SQSTM1) increases deg(p(HGNC:MAPT)) View Subject | View Object

Evidence that p62 facilitates tau degradation has been demonstrated in several studies where p62 colocalized with tau in NFTs from AD patients [53]. PubMed:29758300

Appears in Networks:

p(HGNC:SQSTM1) decreases p(HGNC:MAPT, pmod(HBP:hyperphosphorylation)) View Subject | View Object

For example, Babu et al. has shown that p62−/− knockout mice have increased levels of hyperphosphorylated tau, reduction of synaptophysin and changes in short term memory compared to p62+/− [54] PubMed:29758300

Appears in Networks:

p(HGNC:SQSTM1) increases p(HGNC:SYP) View Subject | View Object

For example, Babu et al. has shown that p62−/− knockout mice have increased levels of hyperphosphorylated tau, reduction of synaptophysin and changes in short term memory compared to p62+/− [54] PubMed:29758300

Appears in Networks:

p(HGNC:SQSTM1) regulates bp(GO:"short-term memory") View Subject | View Object

For example, Babu et al. has shown that p62−/− knockout mice have increased levels of hyperphosphorylated tau, reduction of synaptophysin and changes in short term memory compared to p62+/− [54] PubMed:29758300

Appears in Networks:

p(HGNC:SQSTM1) increases bp(GO:autophagy) View Subject | View Object

For example, p62, an adaptor protein for autophagy, also influences proteasomal degradation, whereas VCP/p97 acting through p62 and ubiquitin regulates both the proteasome-dependent endoplasmic reticulum–associated degradation (ERAD) pathway and aspects of autophagosome maturation (Tresse et al. 2010). PubMed:22908190

Appears in Networks:

p(HGNC:SQSTM1) association bp(GO:"proteasomal protein catabolic process") View Subject | View Object

For example, p62, an adaptor protein for autophagy, also influences proteasomal degradation, whereas VCP/p97 acting through p62 and ubiquitin regulates both the proteasome-dependent endoplasmic reticulum–associated degradation (ERAD) pathway and aspects of autophagosome maturation (Tresse et al. 2010). PubMed:22908190

Appears in Networks:

p(HGNC:SQSTM1) regulates bp(GO:autophagy) View Subject | View Object

Although the mechanism whereby autophagy and UPS function are coordinated is little understood, several regulators have emerged as important players in mediating this crosstalk, including histone deacetylase 6 (HDAC6) [50,64,75], p62/sequestosome 1 (p62) [76], and the FYVE-domain containing protein Alfy [77]; notably, these proteins have all been found to regulate or be essential for aggresome formation PubMed:18930136

Appears in Networks:

p(HGNC:SQSTM1) increases bp(GO:autophagy) View Subject | View Object

Thus, it has been suggested that p62 provides a key link between autophagy and the UPS by facilitating autophagic degradation of ubiquitinated proteins. PubMed:18930136

Appears in Networks:

p(HGNC:SQSTM1) increases bp(GO:autophagy) View Subject | View Object

Recent models propose that p62 and HDAC6 function analogously to facilitate autophagic degradation of proteins that display specific polyubiquitin topology. PubMed:18930136

Appears in Networks:

p(HGNC:SQSTM1) regulates bp(GO:"proteasome-mediated ubiquitin-dependent protein catabolic process") View Subject | View Object

Although the mechanism whereby autophagy and UPS function are coordinated is little understood, several regulators have emerged as important players in mediating this crosstalk, including histone deacetylase 6 (HDAC6) [50,64,75], p62/sequestosome 1 (p62) [76], and the FYVE-domain containing protein Alfy [77]; notably, these proteins have all been found to regulate or be essential for aggresome formation PubMed:18930136

Appears in Networks:

p(HGNC:SQSTM1) increases bp(GO:"proteasome-mediated ubiquitin-dependent protein catabolic process") View Subject | View Object

Thus, it has been suggested that p62 provides a key link between autophagy and the UPS by facilitating autophagic degradation of ubiquitinated proteins. PubMed:18930136

Appears in Networks:

p(HGNC:SQSTM1) regulates a(GO:aggresome) View Subject | View Object

Although the mechanism whereby autophagy and UPS function are coordinated is little understood, several regulators have emerged as important players in mediating this crosstalk, including histone deacetylase 6 (HDAC6) [50,64,75], p62/sequestosome 1 (p62) [76], and the FYVE-domain containing protein Alfy [77]; notably, these proteins have all been found to regulate or be essential for aggresome formation PubMed:18930136

Appears in Networks:

p(HGNC:SQSTM1) association a(GO:"Lewy body") View Subject | View Object

p62 localizes to a variety of ubiquitin-positive neuropathological inclusions including Lewy bodies in Parkinson’s disease, neurofibrillary tangles in tauopathies, polyglutamine-expanded huntingtin aggregates in Huntington’s disease, and aggregates of mutant SOD1 in familial amyotrophic lateral sclerosis [85–87]. PubMed:18930136

Appears in Networks:
Annotations
MeSH
Parkinson Disease

p(HGNC:SQSTM1) association a(GO:"neurofibrillary tangle") View Subject | View Object

p62 localizes to a variety of ubiquitin-positive neuropathological inclusions including Lewy bodies in Parkinson’s disease, neurofibrillary tangles in tauopathies, polyglutamine-expanded huntingtin aggregates in Huntington’s disease, and aggregates of mutant SOD1 in familial amyotrophic lateral sclerosis [85–87]. PubMed:18930136

Appears in Networks:
Annotations
MeSH
Alzheimer Disease

p(HGNC:SQSTM1) association p(HGNC:SOD1, var("?")) View Subject | View Object

p62 localizes to a variety of ubiquitin-positive neuropathological inclusions including Lewy bodies in Parkinson’s disease, neurofibrillary tangles in tauopathies, polyglutamine-expanded huntingtin aggregates in Huntington’s disease, and aggregates of mutant SOD1 in familial amyotrophic lateral sclerosis [85–87]. PubMed:18930136

Appears in Networks:
Annotations
MeSH
Amyotrophic Lateral Sclerosis

p(HGNC:SQSTM1) increases deg(p(MESH:Proteins, pmod(Ub))) View Subject | View Object

Thus, it has been suggested that p62 provides a key link between autophagy and the UPS by facilitating autophagic degradation of ubiquitinated proteins. PubMed:18930136

Appears in Networks:

p(HGNC:SQSTM1) increases bp(GO:"ubiquitin-dependent protein catabolic process") View Subject | View Object

Recent models propose that p62 and HDAC6 function analogously to facilitate autophagic degradation of proteins that display specific polyubiquitin topology. PubMed:18930136

Appears in Networks:

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If you find BEL Commons useful in your work, please consider citing: Hoyt, C. T., Domingo-Fernández, D., & Hofmann-Apitius, M. (2018). BEL Commons: an environment for exploration and analysis of networks encoded in Biological Expression Language. Database, 2018(3), 1–11.