巴基斯坦卢比
糖酵解
生物
丙酮酸激酶
厌氧糖酵解
乙酰转移酶
生物化学
激酶
细胞生物学
酶
乙酰化
基因
作者
Jay Singh,Kevin Qian,Jeong Sang Lee,Jinfeng Zhou,Xuemei Han,Bichen Zhang,Qunxiang Ong,Weiming Ni,Mingzuo Jiang,Hai Bin Ruan,Min‐Dian Li,Kaisi Zhang,Zhaobing Ding,Philip Lee,Kamini Singh,Jing Wu,Raimund I. Herzog,Susan M. Kaech,John R. Yates,Weiping Han,Robert S. Sherwin,Yongzhan Nie,Xiaoyong Yang
出处
期刊:Oncogene
[Springer Nature]
日期:2019-09-09
卷期号:39 (3): 560-573
被引量:37
标识
DOI:10.1038/s41388-019-0975-3
摘要
Cancer cells are known to adopt aerobic glycolysis in order to fuel tumor growth, but the molecular basis of this metabolic shift remains largely undefined. O-GlcNAcase (OGA) is an enzyme harboring O-linked β-N-acetylglucosamine (O-GlcNAc) hydrolase and cryptic lysine acetyltransferase activities. Here, we report that OGA is upregulated in a wide range of human cancers and drives aerobic glycolysis and tumor growth by inhibiting pyruvate kinase M2 (PKM2). PKM2 is dynamically O-GlcNAcylated in response to changes in glucose availability. Under high glucose conditions, PKM2 is a target of OGA-associated acetyltransferase activity, which facilitates O-GlcNAcylation of PKM2 by O-GlcNAc transferase (OGT). O-GlcNAcylation inhibits PKM2 catalytic activity and thereby promotes aerobic glycolysis and tumor growth. These studies define a causative role for OGA in tumor progression and reveal PKM2 O-GlcNAcylation as a metabolic rheostat that mediates exquisite control of aerobic glycolysis.
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