期刊
CANCER RESEARCH
卷 74, 期 13, 页码 3630-3642出版社
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/0008-5472.CAN-13-3615
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资金
- NFC 973 [2011CB910600, 2009CB918401]
- NSFC [31071192, 81225016]
- Shanghai Key Basic Research Program [12JC1401100]
- 100 Talents Program of Shanghai Health [XBR2011041]
- Dawn Program of Shanghai Education Commission
- Shanghai Outstanding Academic Leader [13XD1400600]
- 985 Program
- Shanghai Leading Academic Discipline Project [B110]
- Biomedical Core Facility
- Fudan University
- Fudan University Interdisciplinary Research Program of outstanding Ph.D. students Funds
- NIH
Glycolytic enzyme phosphoglycerate mutase (PGAM) plays an important role in coordinating energy production with generation of reducing power and the biosynthesis of nucleotide precursors and amino acids. Inhibition of PGAM by small RNAi or small molecule attenuates cell proliferation and tumor growth. PGAM activity is commonly upregulated in tumor cells, but how PGAM activity is regulated in vivo remains poorly understood. Here we report that PGAM is acetylated at lysine 100 (K100), an active site residue that is invariably conserved from bacteria, to yeast, plant, and mammals. K100 acetylation is detected in fly, mouse, and human cells and in multiple tissues and decreases PGAM2 activity. The cytosolic protein deacetylase sirtuin 2 (SIRT2) deacetylates and activates PGAM2. Increased levels of reactive oxygen species stimulate PGAM2 deacetylation and activity by promoting its interaction with SIRT2. Substitution of endogenous PGAM2 with an acetylation mimetic mutant K100Q reduces cellular NADPH production and inhibits cell proliferation and tumor growth. These results reveal a mechanism of PGAM2 regulation and NADPH homeostasis in response to oxidative stress that impacts cell proliferation and tumor growth. (C)2014 AACR.
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