超氧化物歧化酶1作为一种核转录因子来调节抗氧化应激能力。
Superoxide dismutase 1 acts as a nuclear transcription factor to regulate oxidative stress resistance.
作者信息
Tsang Chi Kwan, Liu Yuan, Thomas Janice, Zhang Yanjie, Zheng X F S
机构信息
1] Rutgers Cancer Institute of New Jersey, Rutgers, the State University of New Jersey, New Brunswick, New Jersey 08903, USA [2] Department of Pharmacology, Robert Wood Johnson Medical School (RWJMS), Rutgers, the State University of New Jersey, 195 Little Albany Street, New Brunswick, New Jersey 08903, USA.
1] Rutgers Cancer Institute of New Jersey, Rutgers, the State University of New Jersey, New Brunswick, New Jersey 08903, USA [2] The Graduate Program in Molecular and Cellular Pharmacology, Rutgers, the State University of New Jersey.
出版信息
Nat Commun. 2014 Mar 19;5:3446. doi: 10.1038/ncomms4446.
Superoxide dismutase 1 (Sod1) has been known for nearly half a century for catalysis of superoxide to hydrogen peroxide. Here we report a new Sod1 function in oxidative signalling: in response to elevated endogenous and exogenous reactive oxygen species (ROS), Sod1 rapidly relocates into the nucleus, which is important for maintaining genomic stability. Interestingly, H2O2 is sufficient to promote Sod1 nuclear localization, indicating that it is responding to general ROS rather than Sod1 substrate superoxide. ROS signalling is mediated by Mec1/ATM and its effector Dun1/Cds1 kinase, through Dun1 interaction with Sod1 and regulation of Sod1 by phosphorylation at S60, 99. In the nucleus, Sod1 binds to promoters and regulates the expression of oxidative resistance and repair genes. Altogether, our study unravels an unorthodox function of Sod1 as a transcription factor and elucidates the regulatory mechanism for its localization.
超氧化物歧化酶1（Sod1）催化超氧化物生成过氧化氢已为人所知近半个世纪。在此，我们报告Sod1在氧化信号传导中的一项新功能：响应内源性和外源性活性氧（ROS）水平升高，Sod1迅速重新定位到细胞核中，这对于维持基因组稳定性很重要。有趣的是，过氧化氢足以促进Sod1的核定位，表明它是对一般ROS作出反应，而不是对Sod1的底物超氧化物作出反应。ROS信号传导由Mec1/ATM及其效应激酶Dun1/Cds1介导，通过Dun1与Sod1相互作用并在S60、99位点对Sod1进行磷酸化调节。在细胞核中，Sod1与启动子结合并调节抗氧化和修复基因的表达。总之，我们的研究揭示了Sod1作为转录因子的非传统功能，并阐明了其定位的调控机制。
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