Gene interactions and pathways from curated databases and text-mining
J Biol Chem 2010, PMID: 20851890

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

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 p44/42 MAPK signaling 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.

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Text Mining Data

mTOR signaling ⊣ DEPTOR: " Resveratrol inhibits mTOR signaling by promoting the interaction between mTOR and DEPTOR "

mTOR signaling ⊣ mTOR: " Resveratrol inhibits mTOR signaling by promoting the interaction between mTOR and DEPTOR "

4E-BP1 → insulin: " 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 p44/42 MAPK signaling pathway "

Akt → insulin: " 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 p44/42 MAPK signaling pathway "

mTORC1 ⊣ mTOR/DEPTOR: " 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 "

mTORC1 ⊣ mTOR/DEPTOR: " 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 "

Manually curated Databases

No curated data.