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p(FPLX:mTORC1)

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Entity

Name
mTORC1
Namespace
FPLX
Namespace Version
20180917
Namespace URL
https://raw.githubusercontent.com/sorgerlab/famplex/e8ae9926ff95266032cb74f77973c84939bffbeb/export/famplex.belns

Appears in Networks 4

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

Tau degradation: the ubiquitin-proteasome system versus the autophagy-lysosome system. v1.0.0

TFEB enhances astroglial uptake of extracellular tau species and reduces tau spreading v1.0.0

In-Edges 8

a(CHEBI:sirolimus) decreases act(p(FPLX:mTORC1)) View Subject | View Object

Treatment of cell, Drosophila, and mouse models of HD, SCA3/MJD, AD, PD, and ALS with the mTOR inhibitor rapamycin (or a derivative) reduces aggregation and suppresses disease (140– 143). PubMed:25784053

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

a(CHEBI:cilostazol) decreases p(FPLX:mTORC1) View Subject | View Object

Cilostazol (a phosphodiesterase 3 inhibitor) clears Aβ42 from neuronal cell lines by promoting autophagy, upregulating beclin 1, ATG5 and LC3, downregulating mTORC1 and inducing lysosomal cathepsin B; these actions of cilostazol involve activation of SIRT1 as well as upstream Tyr172 phosphorylation of AMPK 108,162,163 . PubMed:30116051

Appears in Networks:
Annotations
MeSH
Dopaminergic Neurons
MeSH
Machado-Joseph Disease

a(CHEBI:curcumin) decreases act(p(FPLX:mTORC1)) View Subject | View Object

The natural product curcumin induced macro- autophagy and protected rotenone-treated dopaminer- gic neurons 141 in addition to accelerating the elimination of mutant α-synuclein-A53T by repressing mTORC1 in a cellular model of early-onset PD, although it also exerts other actions such as inhibition of p300-mediated pro- tein acetylation and of aggregation 142,143 . PubMed:30116051

Appears in Networks:
Annotations
MeSH
Dopaminergic Neurons
MeSH
Machado-Joseph Disease

a(CHEBI:fisetin) increases act(p(FPLX:mTORC1)) View Subject | View Object

Moreover, the flavonol fisetin stimulated auto- phagic degradation of phosphorylated tau in cortical neu- rons via mTORC1-dependent activation of TFEB and the cytoprotective transcription factor nuclear factor eryth- roid 2-related factor 2 (NFE2L2) 149 . Fisetin also reduced Aβ accumulation in an APP/PS1 mouse model of AD 150 . PubMed:30116051

Appears in Networks:
Annotations
MeSH
Dopaminergic Neurons
MeSH
Machado-Joseph Disease

complex(a(CHEBI:sirolimus), p(HGNC:FKBP1A)) decreases act(p(FPLX:mTORC1)) View Subject | View Object

This kinase is classically inactivated by rapamycin, which binds to the modulatory protein 12 kDa FK506-binding protein (FKBP12; also known as FKBP1A). PubMed:30116051

Appears in Networks:
Annotations
MeSH
Dopaminergic Neurons

p(FPLX:mTORC1, pmod(Ph)) decreases act(p(FPLX:mTORC1)) View Subject | View Object

AMPK is central to several mechanisms that trigger autophagy — most importantly, activating phosphoryla- tion of ULK1 (Ser317 and Ser777) and inhibitory phos- phorylation of mTORC1 (REFS21,31) . PubMed:30116051

Appears in Networks:

act(p(HGNC:SIRT1)) decreases act(p(FPLX:mTORC1)) View Subject | View Object

SIRT1 is activated by AMPK- mediated increases in nicotinamide, and it drives the ALN by inhibiting mTORC1, inducing FOXO1 and FOXO3 and activating key regulatory proteins such as ATG5, ATG7 and LC3. PubMed:30116051

Appears in Networks:

p(FPLX:AMPK) decreases act(p(FPLX:mTORC1)) View Subject | View Object

The mammalian target of rapamycin (mTOR) kinase negatively modulates autophagy by phosphorylating Atg1, an autophagy initiating factor, while adenosine monophosphate-activated protein kinase (AMPK), a major sensor for the cellular energy status, activates autophagy through inhibiting mTOR signaling as well as by direct phosphorylation of Atg1 (Egan et al., 2011; Kim et al., 2011). Increased mTOR activity results in autophagy downregulation and tau accumulation. PubMed:23528736

Appears in Networks:

Out-Edges 14

p(FPLX:mTORC1) increases p(HGNC:ULK1, pmod(Ph, Ser, 757)) View Subject | View Object

Conversely, mTORC1 inhibits ULK1 by Ser757 phosphorylation 3,4,31 . PubMed:30116051

Appears in Networks:

p(FPLX:mTORC1) hasVariant p(FPLX:mTORC1, pmod(Ph)) View Subject | View Object

Appears in Networks:

p(FPLX:mTORC1) increases bp(GO:macroautophagy) View Subject | View Object

The heterotrimeric serine/threonine kinase 5ʹ‑AMP‑ activated protein kinase (AMPK) and mammalian target of rapamycin complex 1 (mTORC1) trigger autophagy and repress mitophagy 3,10,20–23 (BOX 2; FIG. 3) . PubMed:30116051

Appears in Networks:

p(FPLX:mTORC1) decreases bp(GO:macroautophagy) View Subject | View Object

One major strategy for promoting autophagy is the relief of its repression by mTORC1. PubMed:30116051

Appears in Networks:
Annotations
MeSH
Dopaminergic Neurons

p(FPLX:mTORC1) decreases bp(GO:mitophagy) View Subject | View Object

The heterotrimeric serine/threonine kinase 5ʹ‑AMP‑ activated protein kinase (AMPK) and mammalian target of rapamycin complex 1 (mTORC1) trigger autophagy and repress mitophagy 3,10,20–23 (BOX 2; FIG. 3) . PubMed:30116051

Appears in Networks:

p(FPLX:mTORC1) decreases tloc(p(HGNC:TFEB), fromLoc(MESH:Cytoplasm), toLoc(MESH:"Cell Nucleus")) View Subject | View Object

mTORC1 also restrains autophagy by preventing nuclear translo- cation of TFEB 20 . PubMed:30116051

Appears in Networks:

act(p(FPLX:mTORC1)) increases act(p(HGNC:TFEB)) View Subject | View Object

Moreover, the flavonol fisetin stimulated auto- phagic degradation of phosphorylated tau in cortical neu- rons via mTORC1-dependent activation of TFEB and the cytoprotective transcription factor nuclear factor eryth- roid 2-related factor 2 (NFE2L2) 149 . Fisetin also reduced Aβ accumulation in an APP/PS1 mouse model of AD 150 . PubMed:30116051

Appears in Networks:
Annotations
MeSH
Dopaminergic Neurons
MeSH
Machado-Joseph Disease

act(p(FPLX:mTORC1)) increases act(p(HGNC:NFE2L2)) View Subject | View Object

Moreover, the flavonol fisetin stimulated auto- phagic degradation of phosphorylated tau in cortical neu- rons via mTORC1-dependent activation of TFEB and the cytoprotective transcription factor nuclear factor eryth- roid 2-related factor 2 (NFE2L2) 149 . Fisetin also reduced Aβ accumulation in an APP/PS1 mouse model of AD 150 . PubMed:30116051

Appears in Networks:
Annotations
MeSH
Dopaminergic Neurons
MeSH
Machado-Joseph Disease

p(FPLX:mTORC1) decreases bp(GO:"proteasome-mediated ubiquitin-dependent protein catabolic process") View Subject | View Object

Finally, mirroring its inhibitory influence on the ALN, mTORC1 suppresses the UPS by impeding the formation and assembly of proteasomal subunits. PubMed:30116051

Appears in Networks:

p(FPLX:mTORC1) decreases bp(GO:"proteasome assembly") View Subject | View Object

Finally, mirroring its inhibitory influence on the ALN, mTORC1 suppresses the UPS by impeding the formation and assembly of proteasomal subunits. PubMed:30116051

Appears in Networks:

p(FPLX:mTORC1) decreases bp(GO:autophagy) View Subject | View Object

The mammalian target of rapamycin (mTOR) kinase negatively modulates autophagy by phosphorylating Atg1, an autophagy initiating factor, while adenosine monophosphate-activated protein kinase (AMPK), a major sensor for the cellular energy status, activates autophagy through inhibiting mTOR signaling as well as by direct phosphorylation of Atg1 (Egan et al., 2011; Kim et al., 2011). Increased mTOR activity results in autophagy downregulation and tau accumulation. PubMed:23528736

Appears in Networks:

act(p(FPLX:mTORC1), ma(kin)) increases p(HGNC:ULK1, pmod(Ph)) View Subject | View Object

The mammalian target of rapamycin (mTOR) kinase negatively modulates autophagy by phosphorylating Atg1, an autophagy initiating factor, while adenosine monophosphate-activated protein kinase (AMPK), a major sensor for the cellular energy status, activates autophagy through inhibiting mTOR signaling as well as by direct phosphorylation of Atg1 (Egan et al., 2011; Kim et al., 2011). Increased mTOR activity results in autophagy downregulation and tau accumulation. PubMed:23528736

Appears in Networks:

act(p(FPLX:mTORC1)) increases p(HGNC:MAPT) View Subject | View Object

The mammalian target of rapamycin (mTOR) kinase negatively modulates autophagy by phosphorylating Atg1, an autophagy initiating factor, while adenosine monophosphate-activated protein kinase (AMPK), a major sensor for the cellular energy status, activates autophagy through inhibiting mTOR signaling as well as by direct phosphorylation of Atg1 (Egan et al., 2011; Kim et al., 2011). Increased mTOR activity results in autophagy downregulation and tau accumulation. PubMed:23528736

Appears in Networks:

p(FPLX:mTORC1) increases p(MGI:Tfeb, pmod(Ph)) View Subject | View Object

Inhibiting mTORC1 blocks the phosphor- ylation of TFEB, allowing unphosphorylated TFEB to translocate to the nucleus and become transcriptionally active PubMed:30108137

Appears in Networks:
Annotations
Cell Ontology (CL)
astrocyte

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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 PyBEL, an open source project. Please feel free to contact us here to give us feedback or report any issues. Also, see our Publishing Notes and Data Protection information.

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.