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SIRT1 negatively regulates the mammalian target of rapamycin

Academic Article
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Overview

authors

  • Ghosh, H. S.
  • McBurney, M.
  • Robbins, Paul D.

publication date

  • February 2010

journal

  • PLoS One  Journal

abstract

  • 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.

subject areas

  • Animals
  • Antioxidants
  • Blotting, Western
  • Cell Line
  • Cells, Cultured
  • Fibroblasts
  • HeLa Cells
  • Humans
  • Immunoprecipitation
  • Intracellular Signaling Peptides and Proteins
  • Jurkat Cells
  • Mice
  • Mice, Knockout
  • Models, Biological
  • Niacinamide
  • Protein Binding
  • Protein-Serine-Threonine Kinases
  • RNA Interference
  • Signal Transduction
  • Sirtuin 1
  • Stilbenes
  • TOR Serine-Threonine Kinases
  • Tumor Suppressor Proteins
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Identity

PubMed Central ID

  • PMC2821410

International Standard Serial Number (ISSN)

  • 1932-6203

Digital Object Identifier (DOI)

  • 10.1371/journal.pone.0009199

PubMed ID

  • 20169165
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Additional Document Info

start page

  • e9199

volume

  • 5

issue

  • 2

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