SIRT1 negatively regulates the mammalian target of rapamycin.
SIRT1 negatively regulates the mammalian target of rapamycin.
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DOI：
10.1371/journal.pone.0009199
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发表时间：
2010-02-15
期刊：
影响因子：
3.7
通讯作者：
Robbins PD
中科院分区：
文献类型：
--
作者：
Ghosh HS;McBurney M;Robbins PD
IGF/mTOR通路受营养素、生长因子、能量状态和细胞应激调节，调节各种生物体的衰老。SIRT 1是一种NAD+依赖性脱乙酰酶，已知其在模型生物中调节热量限制介导的寿命，并且还与胰岛素/IGF信号传导途径相关。在这里，我们研究了SIRT 1对mTOR信号转导的潜在调节，以响应营养和细胞应激。我们证明SIRT 1缺陷导致mTOR信号传导升高，这不会被应激条件所消除。SIRT 1激活剂白藜芦醇降低，而SIRT 1抑制剂烟酰胺以SIRT 1依赖性方式增强mTOR活性。此外，我们证明了SIRT 1与TSC 2相互作用，TSC 2是mTORC 1上游mTOR神经元复合物的一个组成部分，并以TSC 2依赖的方式调节mTOR信号传导。这些结果表明SIRT 1可能通过TSC 1/2复合物负调节mTOR信号传导。
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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发表时间：
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影响因子：
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通讯作者：
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