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Enoyl-CoA hydratase-1 regulates mTOR signaling and apoptosis by sensing nutrients

Nat Commun. 2016; 
Zhang YK, , Qu YY, Lin Y, Wu XH, Chen HZ, Wang X, Zhou KQ, Wei Y, Guo F, Yao CF, He XD, Liu LX, Yang C, Guan ZY, Wang SD, Zhao J, Liu DP, Zhao SM, , Xu W, .
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Catalog Antibody A00702, 1:5000, Genscript), α-ECHS1(cat. Get A Quote

摘要

The oncogenic mechanisms of overnutrition, a confirmed independent cancer risk factor, remain poorly understood. Herein, we report that enoyl-CoA hydratase-1 (ECHS1), the enzyme involved in the oxidation of fatty acids (FAs) and branched-chain amino acids (BCAAs), senses nutrients and promotes mTOR activation and apoptotic resistance. Nutrients-promoted acetylation of lys101 of ECHS1 impedes ECHS1 activity by impairing enoyl-CoA binding, promoting ECHS1 degradation and blocking its mitochondrial translocation through inducing ubiquitination. As a result, nutrients induce the accumulation of BCAAs and FAs that activate mTOR signaling and stimulate apoptosis, respectively. The latter was overcome by selection o... More

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