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SIRT1 negatively regulates the mammalian target of rapamycin

Ghosh, HS and McBurney, M and Robbins, PD (2010) SIRT1 negatively regulates the mammalian target of rapamycin. PLoS ONE, 5 (2).

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The IGF/mTOR pathway, which is modulated by nutrients, growth factors, energy status and cellular stress regulates aging in various organisms. SIRT1 is a NAD+ dependent deacetylase that is known to regulate caloric restriction mediated longevity in model organisms, and has also been linked to the insulin/IGF signaling pathway. Here we investigated the potential regulation of mTOR signaling by SIRT1 in response to nutrients and cellular stress. We demonstrate that SIRT1 deficiency results in elevated mTOR signaling, which is not abolished by stress conditions. The SIRT1 activator resveratrol reduces, whereas SIRT1 inhibitor nicotinamide enhances mTOR activity in a SIRT1 dependent manner. Furthermore, we demonstrate that SIRT1 interacts with TSC2, a component of the mTOR inhibitory-complex upstream to mTORC1, and regulates mTOR signaling in a TSC2 dependent manner. These results demonstrate that SIRT1 negatively regulates mTOR signaling potentially through the TSC1/2 complex. © 2010 Ghosh et al.


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Item Type: Article
Status: Published
CreatorsEmailPitt UsernameORCID
Ghosh, HS
McBurney, M
Robbins, PDprobb@pitt.eduPROBB
ContributionContributors NameEmailPitt UsernameORCID
Date: 15 February 2010
Date Type: Publication
Journal or Publication Title: PLoS ONE
Volume: 5
Number: 2
DOI or Unique Handle: 10.1371/journal.pone.0009199
Refereed: Yes
MeSH Headings: Animals; Antioxidants--pharmacology; Blotting, Western; Cell Line; Cells, Cultured; Fibroblasts--cytology; Fibroblasts--drug effects; Fibroblasts--metabolism; HeLa Cells; Humans; Immunoprecipitation; Intracellular Signaling Peptides and Proteins--metabolism; Jurkat Cells; Mice; Mice, Knockout; Models, Biological; Niacinamide--pharmacology; Protein Binding; Protein-Serine-Threonine Kinases--metabolism; RNA Interference; Signal Transduction--drug effects; Signal Transduction--physiology; Sirtuin 1--genetics; Sirtuin 1--metabolism; Sirtuin 1--physiology; Stilbenes--pharmacology; TOR Serine-Threonine Kinases; Tumor Suppressor Proteins--genetics; Tumor Suppressor Proteins--metabolism
Other ID: NLM PMC2821410
PubMed Central ID: PMC2821410
PubMed ID: 20169165
Date Deposited: 03 Aug 2012 18:41
Last Modified: 26 Jan 2019 17:55


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