Acetylation Targets the M2 Isoform of Pyruvate Kinase for Degradation through Chaperone-Mediated Autophagy and Promotes Tumor Growth

被引：535

作者：

Lv, Lei ^{[1
,3
,4
]}

Li, Dong ^{[5
]}

Zhao, Di ^{[3
,4
]}

Lin, Ruiting ^{[3
,4
]}

Chu, Yajing ^{[6
]}

Zhang, Heng ^{[1
,3
,4
]}

Zha, Zhengyu ^{[3
]}

Liu, Ying ^{[2
]}

Li, Zi ^{[7
]}

Xu, Yanping ^{[3
,4
]}

Wang, Gang ^{[6
]}

Huang, Yiran ^{[5
]}

Xiong, Yue ^{[3
,4
,8
]}

Guan, Kun-Liang ^{[1
,3
,9
,10
]}

Lei, Qun-Ying ^{[1
,3
]}

机构：

[1] Fudan Univ, Shanghai Med Coll, Dept Biochem & Mol Biol, Key Lab Mol Med,Minist Educ, Shanghai 200032, Peoples R China

[2] Fudan Univ, Shanghai Med Coll, Dept Pathol, Shanghai 200032, Peoples R China

[3] Fudan Univ, Inst Biomed Sci, Mol & Cell Biol Lab, Shanghai 200032, Peoples R China

[4] Fudan Univ, Sch Life Sci, Shanghai 200433, Peoples R China

[5] Shanghai Jiao Tong Univ, Ren Ji Hosp, Dept Urol, Shanghai 200127, Peoples R China

[6] Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Biochem & Cell Biol, Shanghai 200031, Peoples R China

[7] Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Nutr Sci, Shanghai 200031, Peoples R China

[8] Univ N Carolina, Lineberger Comprehens Canc Ctr, Dept Biochem & Biophys, Chapel Hill, NC 27599 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

来源：

MOLECULAR CELL | 2011年 / 42卷 / 06期

基金：

美国国家卫生研究院;

关键词：

LYSINE ACETYLATION; LYSOSOMAL PROTEOLYSIS; ALLOSTERIC REGULATION; PEPTIDE SEQUENCES; C-MYC; METABOLISM; PROTEIN; INHIBITION; PROLIFERATION; GLYCOLYSIS;

D O I：

10.1016/j.molcel.2011.04.025

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Most tumor cells take up more glucose than normal cells but metabolize glucose via glycolysis even in the presence of normal levels of oxygen, a phenomenon known as the Warburg effect. Tumor cells commonly express the embryonic M2 isoform of pyruvate kinase (PKM2) that may contribute to the metabolism shift from oxidative phosphorylation to aerobic glycolysis and tumorigenesis. Here we show that PKM2 is acetylated on lysine 305 and that this acetylation is stimulated by high glucose concentration. PKM2 K305 acetylation decreases PKM2 enzyme activity and promotes its lysosomal-dependent degradation via chaperone-mediated autophagy (CMA). Acetylation increases PKM2 interaction with HSC70, a chaperone for CMA, and association with lysosomes. Ectopic expression of an acetylation mimetic K305Q mutant accumulates glycolytic intermediates and promotes cell proliferation and tumor growth. These results reveal an acetylation regulation of pyruvate kinase and the link between lysine acetylation and CMA.

引用

页码：719 / 730

页数：12

共 44 条

[1] Genes of glycolysis are ubiquitously overexpressed in 24 cancer classes [J].