학술논문
O-GlcNAcase targets pyruvate kinase M2 to regulate tumor growth
Document Type
Original Paper
Author
Singh, Jay Prakash; Qian, Kevin; Lee, Jeong-Sang; Zhou, Jinfeng; Han, Xuemei; Zhang, Bichen; Ong, Qunxiang; Ni, Weiming; Jiang, Mingzuo; Ruan, Hai-Bin; Li, Min-Dian; Zhang, Kaisi; Ding, Zhaobing; Lee, Philip; Singh, Kamini; Wu, Jing; Herzog, Raimund I.; Kaech, Susan; Wendel, Hans-Guido; Yates, III, John R.; Han, Weiping; Sherwin, Robert S.; Nie, Yongzhan; Yang, Xiaoyong
Source
Oncogene. 39(3):560-573
Subject
Language
English
ISSN
0950-9232
1476-5594
1476-5594
Abstract
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.