PloS one 2010,
PMID: 20169165
Ghosh, Hiyaa Singhee; McBurney, Michael; Robbins, Paul D
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.
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Text Mining Data
mammalian target of rapamycin → SIRT1: "
SIRT1 negatively
regulates the
mammalian target of rapamycin
"
mTOR signaling — SIRT1: "
Here we investigated the potential regulation of mTOR signaling by SIRT1 in response to nutrients and cellular stress
"
mTOR signaling ⊣ SIRT1: "
We demonstrate that SIRT1 deficiency results in elevated mTOR signaling , which is not abolished by stress conditions
"
mTOR signaling — SIRT1: "
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
"
mTOR signaling → SIRT1: "
These results demonstrate that SIRT1 negatively regulates mTOR signaling potentially through the TSC1/2 complex
"
Manually curated Databases
-
IRef Intact Interaction:
TSC2
—
SIRT1
(physical association, anti bait coimmunoprecipitation)
In total, 1 gene pairs are associated to this article in curated databases