文献类型：期刊文献

英文题名：A redox mechanism underlying nucleolar stress sensing by nucleophosmin

作者：Yang, Kai[1];Wang, Ming[1];Zhao, Yuzheng[2];Sun, Xuxu[1];Yang, Yi[2];Li, Xie[2];Zhou, Aiwu[3];Chu, Huilin[1];Zhou, Hu[4];Xu, Jianrong[5];Wu, Mian[6];Yang, Jie[1];Yi, Jing[1]

机构：[1]Shanghai Jiao Tong Univ, Sch Med,Minist Educ, Dept Biochem & Mol Cell Biol,Key Lab Cell Differe, Shanghai Key Lab Tumor Microenvironm & Inflammat, 280 South Chongqing Rd, Shanghai 200025, Peoples R China;[2]East China Univ Sci & Technol, Sch Pharm, Synthet Biol & Biotechnol Lab, State Key Lab Bioreactor Engn, 130 Mei Long Rd, Shanghai 200237, Peoples R China;[3]Shanghai Jiao Tong Univ, Sch Med, Dept Pathophysiol, 280 South Chongqing Rd, Shanghai 200025, Peoples R China;[4]Shanghai Inst Mat Med, 555 Zu Chong Zhi Rd,Zhang Jiang Hi Tech Pk, Shanghai 201203, Peoples R China;[5]Shanghai Jiao Tong Univ, Sch Med, Dept Pharmacol, 280 South Chongqing Rd, Shanghai 200025, Peoples R China;[6]Univ Sci & Technol China, Sch Life Sci, 96 Jinzhai Rd, Hefei 230022, Anhui, Peoples R China

年份：2016

卷号：7

外文期刊名：NATURE COMMUNICATIONS

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000388641200003)】；

基金：We thank Drs Benjamin Y.M. Yung of The Hong Kong Polytechnic University, Chuanmao Zhang of Peking University and Jim Remington of Oregon State University for their gifts of the plasmids, the pcDNA3.1-FLAG-B23 and the mCherry-C1-H2B and roGFP1, respectively. This work was supported by grants from the National Natural Science Foundation of China (31230037 and 31471263), the Ministry of Science and Technology of China (2013CB910900) and Shanghai Municipal Science and Technology Commission 11JC1406900, 11DZ2260200, 16ZR1418400 and 15YF1402600, the Lift Engineering for Young Talent of China Association for Science and Technology (to Y.Z.).

语种：英文

摘要：The nucleolus has been recently described as a stress sensor. The nucleoplasmic translocation of nucleolar protein nucleophosmin (NPM1) is a hallmark of nucleolar stress; however, the causes of this translocation and its connection to p53 activation are unclear. Using single live-cell imaging and the redox biosensors, we demonstrate that nucleolar oxidation is a general response to various cellular stresses. During nucleolar oxidation, NPM1 undergoes S-glutathionylation on cysteine 275, which triggers the dissociation of NPM1 from nucleolar nucleic acids. The C275S mutant NPM1, unable to be glutathionylated, remains in the nucleolus under nucleolar stress. Compared with wild-type NPM1 that can disrupt the p53-HDM2 interaction, the C275S mutant greatly compromises the activation of p53, highlighting that nucleoplasmic translocation of NPM1 is a prerequisite for stress-induced activation of p53. This study elucidates a redox mechanism for the nucleolar stress sensing and may help the development of therapeutic strategies.