2. Academic Validation
  3. Arginine methylation of ribose-5-phosphate isomerase A senses glucose to promote human colorectal cancer cell survival

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

  • Sci China Life Sci. 2020 Sep;63(9):1394-1405. doi: 10.1007/s11427-019-1562-y.
Jizheng Guo 1,  Qixiang Zhang 1,  Ying Su 2 3,  Xiaochen Lu 2 3,  Yiping Wang 2 3,  Miao Yin 2 3,  Weiguo Hu 2 3,  Wenyu Wen 3,  Qun-Ying Lei 4 5 6 7
Affiliations

Affiliations

  • 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 Department of Biochemistry and Molecular Biology, School of Basic Medical Science, Shanghai Medical College, Fudan University, Shanghai, 200032, China. qlei@fudan.edu.cn.
  • 5 Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China. qlei@fudan.edu.cn.
  • 6 Institutes of Biomedical Sciences, Shanghai Medical College, Fudan University, Shanghai, 200032, China. qlei@fudan.edu.cn.
  • 7 State Key Laboratory of Medical Neurobiology Shanghai Medical College, Fudan University, Shanghai, 200032, China. qlei@fudan.edu.cn.
PMID: 32157557 DOI: 10.1007/s11427-019-1562-y
Abstract

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.

Keywords

CARM1; arginine methylation; colorectal cancer; pentose phosphate pathway; reactive oxygen species; ribose-5-phosphate isomerase A; ribulose-5-phosphate.

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