文献类型：期刊文献

英文题名：Regulation of G6PD acetylation by SIRT2 and KAT9 modulates NADPH homeostasis and cell survival during oxidative stress

作者：Wang, Yi-Ping[1,2];Zhou, Li-Sha[1,2];Zhao, Yu-Zheng[3];Wang, Shi-Wen[1,2];Chen, Lei-Lei[1,2];Liu, Li-Xia[4,5];Ling, Zhi-Qiang[6];Hu, Fu-Jun[7];Sun, Yi-Ping[1,2];Zhang, Jing-Ye[1,2];Yang, Chen[4,5];Yang, Yi[3];Xiong, Yue[1,2,8];Guan, Kun-Liang[1,2,9,10];Ye, Dan[1,2]

机构：[1]Fudan Univ, Coll Life Sci, Shanghai Med Coll, Minist Educ,Key Lab Mol Med, Shanghai 200433, Peoples R China;[2]Fudan Univ, Coll Life Sci, Shanghai Med Coll, Inst Biomed Sci, Shanghai 200433, Peoples R China;[3]E China Univ Sci & Technol, Sch Pharm, Shanghai 200237, Peoples R China;[4]Chinese Acad Sci, Shanghai Inst Biol Sci, Bioinformat Ctr, Key Lab Synthet Biol, Shanghai, Peoples R China;[5]Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Plant Physiol & Ecol, Lab Syst Biol, Shanghai, Peoples R China;[6]Zhejiang Canc Ctr, Zhejiang Prov Canc Hosp, Zhejiang Canc Res Inst, Hangzhou, Zhejiang, Peoples R China;[7]Zhejiang Canc Ctr, Zhejiang Prov Canc Hosp, Dept Radiotherapy, Hangzhou, Zhejiang, Peoples R China;[8]Univ N Carolina, Dept Biochem & Biophys, Lineberger Comprehens Canc Ctr, Chapel Hill, NC USA;[9]Univ Calif San Diego, Dept Pharmacol, La Jolla, CA 92093 USA;[10]Univ Calif San Diego, Moores Canc Ctr, La Jolla, CA 92093 USA

年份：2014

卷号：33

期号：12

起止页码：1304

外文期刊名：EMBO JOURNAL

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000338024100006)】；

基金：We thank the members of the Fudan MCB laboratory for discussions and support throughout this study. In addition, we also thank the Biomedical Core Facility, Fudan University, for technical support throughout this study. This work was supported by the 973 Program ( No. 2012CB910303, No. 2012CB910101, No. 2011CB910600, No. 2009CB918401) and by the Innovation Program of Shanghai Municipal Education Commission ( No. 12ZZ008). This work was also supported by NIH Grants (CA163834 to YX and R01CA108941 to KLG) and James McDonnell Foundation Samuel Waxman Foundation ( to YX).

语种：英文

外文关键词：acetylation; G6PD; nicotinamide adenine dinucleotide phosphate; reactive oxygen species; SIRT2

摘要：Glucose-6-phosphate dehydrogenase (G6PD) is a key enzyme in the pentose phosphate pathway (PPP) and plays an essential role in the oxidative stress response by producing NADPH, the main intracellular reductant. G6PD deficiency is the most common human enzyme defect, affecting more than 400 million people worldwide. Here, we show that G6PD is negatively regulated by acetylation on lysine 403 (K403), an evolutionarily conserved residue. The K403 acetylated G6PD is incapable of forming active dimers and displays a complete loss of activity. Knockdown of G6PD sensitizes cells to oxidative stress, and re-expression of wild-type G6PD, but not the K403 acetylation mimetic mutant, rescues cells from oxidative injury. Moreover, we show that cells sense extracellular oxidative stimuli to decrease G6PD acetylation in a SIRT2-dependent manner. The SIRT2-mediated deacetylation and activation of G6PD stimulates PPP to supply cytosolic NADPH to counteract oxidative damage and protect mouse erythrocytes. We also identified KAT9/ELP3 as a potential acetyltransferase of G6PD. Our study uncovers a previously unknown mechanism by which acetylation negatively regulates G6PD activity to maintain cellular NADPH homeostasis during oxidative stress.