Regulation of SIRT1 activity by genotoxic stress
Regulation of SIRT1 activity by genotoxic stress
复制标题
基因毒性应激对 SIRT1 活性的调节
DOI：
10.1101/gad.188482.112
复制
发表时间：
2012-04-15
影响因子：
10.5
通讯作者：
Lou, Zhenkun
中科院分区：
文献类型：
--
作者：
Yuan, Jian;Luo, Kuntian;Lou, Zhenkun
SIRT 1调节多种细胞功能，包括细胞应激反应和能量代谢。SIRT 1活性由DBC 1（乳腺癌1中的β-内酰胺酶）通过直接结合负调控。然而，如何调控DBC 1-SIRT 1相互作用仍不清楚。我们发现DBC 1-SIRT 1相互作用在DNA损伤和氧化应激后增加。应激诱导的DBC 1-SIRT 1相互作用需要DBC 1在Thr 454处的ATM依赖性磷酸化，这产生了SIRT 1的第二个结合位点。最后，我们表明，压力诱导的DBC 1-SIRT 1相互作用是重要的基因毒性压力后的细胞命运决定。这些结果揭示了SIRT 1在遗传毒性应激过程中的一种新的调节机制。
SIRT1 regulates a variety of cellular functions, including cellular stress responses and energy metabolism. SIRT1 activity is negatively regulated by DBC1 (Deleted in Breast Cancer 1) through direct binding. However, how the DBC1-SIRT1 interaction is regulated remains unclear. We found that the DBC1-SIRT1 interaction increases following DNA damage and oxidative stress. The stress-induced DBC1-SIRT1 interaction requires the ATM-dependent phosphorylation of DBC1 at Thr 454, which creates a second binding site for SIRT1. Finally, we showed that the stress-induced DBC1-SIRT1 interaction is important for cell fate determination following genotoxic stress. These results revealed a novel mechanism of SIRT1 regulation during genotoxic stress.