Arginine methylation of ribose-5-phosphate isomerase A senses glucose to promote human colorectal cancer cell survival  

作　　者：Jizheng Guo Qixiang Zhang Ying Su Xiaochen Lu Yiping Wang Miao Yin Weiguo Hu Wenyu Wen Qun-Ying Lei 

机构地区：[1]Department of Biochemistry and Molecular Biology,School of Basic Medical Science,Shanghai Medical College,Fudan University,Shanghai 200032,China [2]Fudan University Shanghai Cancer Center,Department of Oncology,Shanghai Medical College,Fudan University,Shanghai 200032,China [3]Institutes of Biomedical Sciences,Shanghai Medical College,Fudan University,Shanghai 200032,China [4]State Key Laboratory of Medical Neurobiology Shanghai Medical College,Fudan University,Shanghai 200032,China

出　　处：《Science China(Life Sciences)》2020年第9期1394-1405,共12页中国科学（生命科学英文版）

基　　金：supported by the Ministry of Science and Technology(2019YFA0801703);the National Natural Science Foundation of China(81790250,81790253 and 91959202);the Innovation Program of Shanghai Municipal Education Commission(N173606)。

摘　　要：Cancer cells remodel their metabolic network to adapt to variable nutrient availability. Pentose phosphate pathway(PPP) plays protective and biosynthetic roles by oxidizing glucose to generate reducing power and ribose. How cancer cells modulate PPP activity in response to glucose supply remains unclear. Here we show that ribose-5-phosphate isomerase A(RPIA), an enzyme in PPP, directly interacts with co-activator associated arginine methyltransferase 1(CARM1) and is methylated at arginine 42(R42). R42 methylation up-regulates the catalytic activity of RPIA. Furthermore, glucose deprivation strengthens the binding of CARM1 with RPIA to induce R42 hypermethylation. Insufficient glucose supply links to RPIA hypermethylation at R42, which increases oxidative PPP flux. RPIA methylation supports ROS clearance by enhancing NADPH production and fuels nucleic acid synthesis by increasing ribose supply. Importantly, RPIA methylation at R42 significantly potentiates colorectal cancer cell survival under glucose starvation. Collectively, RPIA methylation connects glucose availability to nucleotide synthesis and redox homeostasis.

关 键 词：ribose-5-phosphate isomerase A CARM1 arginine methylation pentose phosphate pathway ribulose-5-phosphate reactive oxygen species colorectal cancer 

分 类 号：R735.34[医药卫生—肿瘤]