Superoxide dismutase 1 acts as a nuclear transcription factor to regulate oxidative stress resistance

被引：372
作者：
Tsang, Chi Kwan [1 ,2 ]
Liu, Yuan [1 ,3 ]
Thomas, Janice [1 ,2 ]
Zhang, Yanjie [1 ,2 ]
Zheng, X. F. S. [1 ,2 ]
机构：
[1] Rutgers State Univ, Rutgers Canc Inst New Jersey, New Brunswick, NJ 08903 USA
[2] Rutgers State Univ, Robert Wood Johnson Med Sch, Dept Pharmacol, New Brunswick, NJ 08903 USA
[3] Rutgers State Univ, Grad Program Mol & Cellular Pharmacol, New Brunswick, NJ 08903 USA
来源：
NATURE COMMUNICATIONS | 2014年 / 5卷
关键词：
DNA-DAMAGE; SACCHAROMYCES-CEREVISIAE; PHOSPHORYLATION SITES; SOD1; LOCALIZATION; MECHANISMS; IDENTIFICATION; KINASE; REPAIR; OXYGEN;
D O I：
10.1038/ncomms4446
中图分类号：
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号：
07 ; 0710 ; 09 ;
摘要：
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.
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页数：11
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