Lysine Acetylation Activates 6-Phosphogluconate Dehydrogenase to Promote   Tumor Growth

doi:10.1016/j.molcel.2014.06.020

CORC > 北京大学 > 化学与分子工程学院

	Lysine Acetylation Activates 6-Phosphogluconate Dehydrogenase to Promote Tumor Growth
	Shan, Changliang ; Elf, Shannon ; Ji, Quanjiang ; Kang, Hee-Bum ; Zhou, Lu ; Hitosugi, Taro ; Jin, Lingtao ; Lin, Ruiting ; Zhang, Liang ; Seo, Jae Ho ; Xie, Jianxin ; Tucker, Meghan ; Gu, Ting-Lei ; Sudderth, Jessica ; Jiang, Lei ; DeBerardinis, Ralph J. ; Wu, Shaoxiong ; Li, Yuancheng ; Mao, Hui ; Chen, Peng R. ; Wang, Dongsheng ; Chen, Georgia Zhuo ; Lonial, Sagar ; Arellano, Martha L. ; Khoury, Hanna J. ; Khuri, Fadlo R. ; Lee, Benjamin H. ; Brat, Daniel J. ; Ye, Keqiang ; Boggon, Titus J. ; He, Chuan ; Kang, Sumin ; Fan, Jun ; Chen, Jing
刊名	分子细胞
	2014
关键词	TYROSINE PHOSPHORYLATION CELL METABOLISM CANCER COMPLEX
DOI	10.1016/j.molcel.2014.06.020
英文摘要	Although the oxidative pentose phosphate pathway is important for tumor growth, how 6-phosphogluconate dehydrogenase (6PGD) in this pathway is upregulated in human cancers is unknown. We found that 6PGD is commonly activated in EGF-stimulated cells and human cancer cells by lysine acetylation. Acetylation at K76 and K294 of 6PGD promotes NADP(+) binding to 6PGD and formation of active 6PGD dimers, respectively. Moreover, we identified DLAT and ACAT2 as upstream acetyltransferases of K76 and K294, respectively, and HDAC4 as the deacetylase of both sites. Expressing acetyl-deficient mutants of 6PGD in cancer cells significantly attenuated cell proliferation and tumor growth. This is due in part to reduced levels of 6PGD products ribulose-5-phosphate and NADPH, which led to reduced RNA and lipid biosynthesis as well as elevated ROS. Furthermore, 6PGD activity is upregulated with increased lysine acetylation in primary leukemia cells from human patients, providing mechanistic insights into 6PGD upregulation in cancer cells.; Biochemistry & Molecular Biology; Cell Biology; SCI(E); PubMed; 2; ARTICLE; jfan3@emory.edu; jchen@emory.edu; 4; 552-565; 55
语种	英语
内容类型	期刊论文
源URL	[http://ir.pku.edu.cn/handle/20.500.11897/188884]
专题	化学与分子工程学院
推荐引用方式 GB/T 7714	Shan, Changliang,Elf, Shannon,Ji, Quanjiang,et al. Lysine Acetylation Activates 6-Phosphogluconate Dehydrogenase to Promote Tumor Growth[J]. 分子细胞,2014.
APA	Shan, Changliang.,Elf, Shannon.,Ji, Quanjiang.,Kang, Hee-Bum.,Zhou, Lu.,...&Chen, Jing.(2014).Lysine Acetylation Activates 6-Phosphogluconate Dehydrogenase to Promote Tumor Growth.分子细胞.
MLA	Shan, Changliang,et al."Lysine Acetylation Activates 6-Phosphogluconate Dehydrogenase to Promote Tumor Growth".分子细胞 (2014).