Targeting posttranslational modifications of RIOK1 inhibits the progression of colorectal and gastric cancers

• DOI: 10.7554/elife.29511
• Publication Date: 2018-01-31T13:05:59Z
• Authors: Xuehui Hong; He Huang; Xingfeng Qiu; Zhijie Ding; Xing Feng; Yuekun Zhu; Huiqin Zhuo; Jingjing Hou; Jiabao Zhao; Wangyu Cai; Ruihua Sha; Xinya Hong; Yongxiang Li; Hongjiang Song; Zhiyong Zhang
• Keywords: Demethylase

RIOK1 has recently been shown to play important roles in cancers, but its posttranslational regulation is largely unknown. Here we report that methylated at K411 by SETD7 methyltransferase and lysine-specific demethylase 1 (LSD1) reverses methylation. The mutated (K411R) cannot be exhibits a longer half-life than does the RIOK1. FBXO6 specifically interacts with K411-methylated through FBA domain induce ubiquitination. Casein kinase 2 (CK2) phosphorylates T410, which stabilizes antagonizing methylation impeding recruitment of Functional experiments demonstrate reduces tumor growth metastasis mice model. Importantly, protein levels CK2 LSD1 show an inverse correlation expression human colorectal cancer tissues. Together, this study highlights importance methylation-phosphorylation switch determining gastric development.