SHMT2 Desuccinylation by SIRT5 Drives Cancer Cell Proliferation

• Published in: Cancer research (Chicago, Ill.) Vol. 78; no. 2; pp. 372 - 386
• Main Authors: Yang, Xin, Wang, Zhe, Li, Xin, Liu, Boya, Liu, Minghui, Liu, Lu, Chen, Shuaiyi, Ren, Mengmeng, Wang, Yankun, Yu, Miao, Wang, Bo, Zou, Junhua, Zhu, Wei-Guo, Yin, Yuxin, Gu, Wei, Luo, Jianyuan
• Format: Journal Article
• Language: English
• Published: United States American Association for Cancer Research, Inc 15.01.2018
• Subjects: Animals; Apoptosis; Biomarkers, Tumor - genetics; Biomarkers, Tumor - metabolism; Cancer; Cell growth; Cell Proliferation; Colonic Neoplasms - genetics; Colonic Neoplasms - metabolism; Colonic Neoplasms - pathology; CRISPR-Cas Systems; Enzymatic activity; Gene Expression Regulation, Neoplastic; Glycine Hydroxymethyltransferase - antagonists & inhibitors; Glycine Hydroxymethyltransferase - genetics; Glycine Hydroxymethyltransferase - metabolism; Humans; Lysine; Male; Metabolism; Mice; Mice, Inbred BALB C; Mice, Nude; Mitochondria; Protein Processing, Post-Translational; Serine; Serine - metabolism; Sirtuins - genetics; Sirtuins - metabolism; Succinates - chemistry; Succinates - metabolism; Tumor cells; Tumor Cells, Cultured; Xenograft Model Antitumor Assays

The mitochondrial serine hydroxymethyltransferase SHMT2, which catalyzes the rate-limiting step in serine catabolism, drives cancer cell proliferation, but how this role is regulated is undefined. Here, we report that the sirtuin SIRT5 desuccinylates SHMT2 to increase its activity and drive serine c...