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Energy sensor AMPK gamma regulates translation via phosphatase PPP6C independent of AMPK alpha

文献类型：期刊论文

作者Zhou, Qi1,2,3; Hao, Bingbing4; Cao, Xiaolei1,2,3; Gao, Lin1,2,3; Yu, Zhenyue1,2,3; Zhao, Yang1,2,3; Zhu, Mingrui4; Zhong, Guoxuan1,2,3; Chi, Fangtao2,3; Dai, Xiaoming2,3
刊名MOLECULAR CELL
出版日期2022-12-15
卷号82期号:24页码:4700-+
ISSN号1097-2765
DOI10.1016/j.molcel.2022.10.030
通讯作者Feng, Xin-Hua(xhfeng@zju.edu.cn) ; Tan, Minjia(mjtan@simm.ac.cn) ; Zhao, Bin(binzhao@zju.edu.cn)
英文摘要Maintenance of energy level to drive movements and material exchange with the environment is a basic prin-ciple of life. AMP-activated protein kinase (AMPK) senses energy level and is a major regulator of cellular en-ergy responses. The gamma subunit of AMPK senses elevated ratio of AMP to ATP and allosterically acti-vates the alpha catalytic subunit to phosphorylate downstream effectors. Here, we report that knockout of AMPKg, but not AMPKa, suppressed phosphorylation of eukaryotic translation elongation factor 2 (eEF2) induced by energy starvation. We identified PPP6C as an AMPKy-regulated phosphatase of eEF2. AMP -bound AMPKy sequesters PPP6C, thereby blocking dephosphorylation of eEF2 and thus inhibiting transla-tion elongation to preserve energy and to promote cell survival. Further phosphoproteomic analysis identified additional targets of PPP6C regulated by energy stress in an AMPK gamma dependent manner. Thus, AMPKy senses cellular energy availability to regulate not only AMPKa kinase, but also PPP6C phosphatase and possibly other effectors.
WOS关键词ACTIVATED PROTEIN-KINASE ; ELONGATION FACTOR-II ; CARDIAC-HYPERTROPHY ; STRUCTURAL BASIS ; RAG GTPASES ; PHOSPHORYLATION ; SUBUNIT ; DISEASE ; BINDING ; MUTATIONS
资助项目National Key R&D Program of China[2017YFA0504502] ; National Natural Science Foundation of China[81730069] ; National Natural Science Foundation of China[31970726] ; National Natural Science Foundation of China Major Project[92153302] ; Fundamental Research Funds for the Central Universities
WOS研究方向Biochemistry & Molecular Biology ; Cell Biology
语种英语
出版者CELL PRESS
WOS记录号WOS:000919685300001
源URL[http://119.78.100.183/handle/2S10ELR8/303367]  
专题新药研究国家重点实验室
通讯作者Feng, Xin-Hua; Tan, Minjia; Zhao, Bin
作者单位1.Zhejiang Univ, Canc Ctr, Hangzhou 310058, Peoples R China
2.Zhejiang Univ, Life Sci Inst, MOE Key Lab Biosyst Homeostasis & Protect, Zhejiang Prov Key Lab Canc Mol Cell Biol, Hangzhou 310058, Peoples R China
3.Zhejiang Univ, Life Sci Inst, Innovat Ctr Cell Signaling Network, Hangzhou 310058, Peoples R China
4.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China
5.Nanjing Univ, MOE Key Lab Model Anim Dis Study, Model Anim Res Ctr, Nanjing 210061, Peoples R China
6.Nanjing Univ, State Key Lab Pharmaceut Biotechnol, Model Anim Res Ctr, Nanjing 210061, Peoples R China
7.Zhejiang Univ, Affiliated Hosp 1, Sch Med, Dept Hepatobiliary & Pancreat Surg,Zhejiang Prov, Hangzhou 310058, Peoples R China
8.Hangzhou Normal Univ, Inst Aging Res, Hangzhou 311121, Peoples R China
9.Zhejiang Univ, Ctr Life Sci, Shaoxing Inst, Shaoxing 321000, Peoples R China
推荐引用方式
GB/T 7714		 Zhou, Qi,Hao, Bingbing,Cao, Xiaolei,et al. Energy sensor AMPK gamma regulates translation via phosphatase PPP6C independent of AMPK alpha[J]. MOLECULAR CELL,2022,82(24):4700-+.
APA Zhou, Qi.,Hao, Bingbing.,Cao, Xiaolei.,Gao, Lin.,Yu, Zhenyue.,...&Zhao, Bin.(2022).Energy sensor AMPK gamma regulates translation via phosphatase PPP6C independent of AMPK alpha.MOLECULAR CELL,82(24),4700-+.
MLA Zhou, Qi,et al."Energy sensor AMPK gamma regulates translation via phosphatase PPP6C independent of AMPK alpha".MOLECULAR CELL 82.24(2022):4700-+.

入库方式： OAI收割

来源：上海药物研究所

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