Resveratrol inhibits mTOR signaling by promoting the interaction between mTOR and DEPTOR

Meilian Liu, Sarah Ann Wilk, Anping Wang, Lijun Zhou, Rui Hong Wang, Wataru Ogawa, Chuxia Deng, Lily Q Dong, Feng Liu

Research output: Contribution to journalArticle

112 Citations (Scopus)

Abstract

Resveratrol (RSV) is a naturally occurring polyphenol that has been found to exert antioxidant, anti-inflammatory, and neuroprotective properties. However, how RSV exerts its beneficial health effects remains largely unknown. Here, we show that RSV inhibits insulin- and leucine-stimulated mTOR signaling in C2C12 fibroblasts via a Sirt1-independent mechanism. Treating C2C12 cells with RSV dramatically inhibited insulin-stimulated Akt, S6 kinase, and 4E-BP1 phosphorylation but had little effect on tyrosine phosphorylation of the insulin receptor and activation of the p44/42MAPKsignaling pathway. RSV treatment also partially blocked mTOR and S6 kinase phosphorylation in TSC1/2-deficient mouse embryonic fibroblasts, suggesting the presence of an inhibitory site downstream of TSC1/2. Knocking out PDK1 or suppressing AMP-activated protein kinase had little effect on leucine-stimulated mTOR signaling. On the other hand, RSV significantly increased the association between mTOR and its inhibitor, DEPTOR. Furthermore, the inhibitory effect of RSV on leucine-stimulated mTOR signaling was greatly reduced in cells in which the expression levels of DEPTOR were suppressed by RNAi. Taken together, our studies reveal that RSV inhibits leucine-stimulated mTORC1 activation by promoting mTOR/DEPTOR interaction and thus uncover a novel mechanism by which RSV negatively regulates mTOR activity.

Original languageEnglish (US)
Pages (from-to)36387-36394
Number of pages8
JournalJournal of Biological Chemistry
Volume285
Issue number47
DOIs
StatePublished - Nov 19 2010

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Leucine
Phosphorylation
Ribosomal Protein S6 Kinases
Fibroblasts
Chemical activation
Insulin
resveratrol
AMP-Activated Protein Kinases
Insulin Receptor
Polyphenols
RNA Interference
Tyrosine
Anti-Inflammatory Agents
Antioxidants
Health
Association reactions

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

Resveratrol inhibits mTOR signaling by promoting the interaction between mTOR and DEPTOR. / Liu, Meilian; Wilk, Sarah Ann; Wang, Anping; Zhou, Lijun; Wang, Rui Hong; Ogawa, Wataru; Deng, Chuxia; Dong, Lily Q; Liu, Feng.

In: Journal of Biological Chemistry, Vol. 285, No. 47, 19.11.2010, p. 36387-36394.

Research output: Contribution to journalArticle

Liu, Meilian ; Wilk, Sarah Ann ; Wang, Anping ; Zhou, Lijun ; Wang, Rui Hong ; Ogawa, Wataru ; Deng, Chuxia ; Dong, Lily Q ; Liu, Feng. / Resveratrol inhibits mTOR signaling by promoting the interaction between mTOR and DEPTOR. In: Journal of Biological Chemistry. 2010 ; Vol. 285, No. 47. pp. 36387-36394.
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