GONUTS has been updated to MW1.31 Most things seem to be working but be sure to report problems.
PMID:22958918
| Citation |
Lee, JH, Budanov, AV, Talukdar, S, Park, EJ, Park, HL, Park, HW, Bandyopadhyay, G, Li, N, Aghajan, M, Jang, I, Wolfe, AM, Perkins, GA, Ellisman, MH, Bier, E, Scadeng, M, Foretz, M, Viollet, B, Olefsky, J and Karin, M (2012) Maintenance of metabolic homeostasis by sestrin2 and sestrin3. Cell Metab. 16:311-21 |
|---|---|
| Abstract |
Chronic activation of mammalian target of rapamycin complex 1 (mTORC1) and p70 S6 kinase (S6K) in response to hypernutrition contributes to obesity-associated metabolic pathologies, including hepatosteatosis and insulin resistance. Sestrins are stress-inducible proteins that activate AMP-activated protein kinase (AMPK) and suppress mTORC1-S6K activity, but their role in mammalian physiology and metabolism has not been investigated. We show that Sestrin2-encoded by the Sesn2 locus, whose expression is induced upon hypernutrition-maintains metabolic homeostasis in liver of obese mice. Sesn2 ablation exacerbates obesity-induced mTORC1-S6K activation, glucose intolerance, insulin resistance, and hepatosteatosis, all of which are reversed by AMPK activation. Furthermore, concomitant ablation of Sesn2 and Sesn3 provokes hepatic mTORC1-S6K activation and insulin resistance even in the absence of nutritional overload and obesity. These results demonstrate an important homeostatic function for the stress-inducible Sestrin protein family in the control of mammalian lipid and glucose metabolism. |
| Links |
PubMed Online version:10.1016/j.cmet.2012.08.004 |
| Keywords |
|
| edit table |
Significance
Annotations
| Gene product | Qualifier | GO Term | Evidence Code | with/from | Aspect | Extension | Notes | Status |
|---|---|---|---|---|---|---|---|---|
|
MOUSE:LEP |
acts_upstream_of_or_within |
GO:0006635: fatty acid beta-oxidation |
ECO:0000316: genetic interaction evidence used in manual assertion |
MGI:MGI:2651874 |
P |
Seeded From UniProt |
complete | |
|
MOUSE:LEP |
acts_upstream_of_or_within |
GO:0042593: glucose homeostasis |
ECO:0000316: genetic interaction evidence used in manual assertion |
MGI:MGI:2651874 |
P |
Seeded From UniProt |
complete | |
|
MOUSE:SESN1 |
acts_upstream_of_or_within |
GO:0051896: regulation of protein kinase B signaling |
ECO:0000314: direct assay evidence used in manual assertion |
P |
Seeded From UniProt |
complete | ||
|
MOUSE:SESN3 |
acts_upstream_of_or_within |
GO:0032868: response to insulin |
ECO:0000316: genetic interaction evidence used in manual assertion |
MGI:MGI:2651874 |
P |
Seeded From UniProt |
complete | |
|
MOUSE:SESN3 |
acts_upstream_of_or_within |
GO:0051896: regulation of protein kinase B signaling |
ECO:0000314: direct assay evidence used in manual assertion |
P |
Seeded From UniProt |
complete | ||
|
MOUSE:SESN3 |
acts_upstream_of_or_within |
GO:0042593: glucose homeostasis |
ECO:0000316: genetic interaction evidence used in manual assertion |
MGI:MGI:2651874 |
P |
Seeded From UniProt |
complete | |
|
acts_upstream_of_or_within |
GO:0032868: response to insulin |
ECO:0000316: genetic interaction evidence used in manual assertion |
MGI:MGI:104663 |
P |
Seeded From UniProt |
complete | ||
|
acts_upstream_of_or_within |
GO:0042593: glucose homeostasis |
ECO:0000316: genetic interaction evidence used in manual assertion |
MGI:MGI:104663 |
P |
Seeded From UniProt |
complete | ||
| GO:0010255 : glucose mediated signaling pathway |
ECO:0000314: |
P |
Figure 1A and 1B show that a deficiency in SESN2 had a great effect on the activation and production of Glucose. |
complete | ||||
| GO:0000723: telomere maintenance |
ECO:0000021: |
UniProtKB:Q9Y478
|
P |
From the graphical abstract one can see that SESN2 would be used as an activating and maintainer of AMPK. This is also seen in figure one where the concentration of SESN2 effects the activation of AMPK |
complete | |||
|
acts_upstream_of_or_within |
GO:0006111: regulation of gluconeogenesis |
ECO:0000315: mutant phenotype evidence used in manual assertion |
MGI:MGI:3587950 |
P |
Seeded From UniProt |
complete | ||
|
acts_upstream_of_or_within |
GO:0009749: response to glucose |
ECO:0000316: genetic interaction evidence used in manual assertion |
MGI:MGI:104663 |
P |
Seeded From UniProt |
complete | ||
|
acts_upstream_of_or_within |
GO:0009749: response to glucose |
ECO:0000315: mutant phenotype evidence used in manual assertion |
MGI:MGI:3587950 |
P |
Seeded From UniProt |
complete | ||
|
acts_upstream_of_or_within |
GO:0007005: mitochondrion organization |
ECO:0000315: mutant phenotype evidence used in manual assertion |
MGI:MGI:3587950 |
P |
Seeded From UniProt |
complete | ||
|
acts_upstream_of_or_within |
GO:0006635: fatty acid beta-oxidation |
ECO:0000316: genetic interaction evidence used in manual assertion |
MGI:MGI:104663 |
P |
Seeded From UniProt |
complete | ||
|
acts_upstream_of_or_within |
GO:0001932: regulation of protein phosphorylation |
ECO:0000315: mutant phenotype evidence used in manual assertion |
MGI:MGI:3587950 |
P |
Seeded From UniProt |
complete | ||
|
acts_upstream_of_or_within |
GO:0032042: mitochondrial DNA metabolic process |
ECO:0000315: mutant phenotype evidence used in manual assertion |
MGI:MGI:3587950 |
P |
Seeded From UniProt |
complete | ||
|
acts_upstream_of_or_within |
GO:0032868: response to insulin |
ECO:0000315: mutant phenotype evidence used in manual assertion |
MGI:MGI:3587950 |
P |
Seeded From UniProt |
complete | ||
|
acts_upstream_of_or_within |
GO:0043491: protein kinase B signaling |
ECO:0000315: mutant phenotype evidence used in manual assertion |
MGI:MGI:3587950 |
P |
Seeded From UniProt |
complete | ||
|
acts_upstream_of_or_within |
GO:0046323: glucose import |
ECO:0000315: mutant phenotype evidence used in manual assertion |
MGI:MGI:3587950 |
P |
Seeded From UniProt |
complete | ||
|
acts_upstream_of_or_within |
GO:0070328: triglyceride homeostasis |
ECO:0000315: mutant phenotype evidence used in manual assertion |
MGI:MGI:3587950 |
P |
Seeded From UniProt |
complete | ||
|
acts_upstream_of_or_within |
GO:1904504: positive regulation of lipophagy |
ECO:0000315: mutant phenotype evidence used in manual assertion |
MGI:MGI:3587950 |
P |
Seeded From UniProt |
complete | ||
|
acts_upstream_of_or_within |
GO:2000479: regulation of cAMP-dependent protein kinase activity |
ECO:0000315: mutant phenotype evidence used in manual assertion |
MGI:MGI:3587950 |
P |
Seeded From UniProt |
complete | ||
See also
References
See Help:References for how to manage references in GONUTS.
g
r
