Targeting Posttranslational Modifications of RIOK1 Inhibits the Progression of Colorectal and Gastric Cancers

Overview

Journal Elife

Specialty Biology

Date 2018 Feb 1

PMID 29384474

Citations 32

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

Affiliations

Soon will be listed here.

Abstract

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

Citing Articles

The multifaceted role of post-translational modifications of LSD1 in cellular processes and disease pathogenesis.

Li Y, Wang B, Zheng Y, Kang H, He A, Zhao L Genes Dis. 2025; 12(3):101307.

PMID: 40028036 PMC: 11870172. DOI: 10.1016/j.gendis.2024.101307.

SETD7 promotes LC3B methylation and degradation in ovarian cancer.

Zhang Z, Li M, Hou Y, Huang T, Zhang B, Lin Q J Biol Chem. 2024; 301(2):108134.

PMID: 39725038 PMC: 11791264. DOI: 10.1016/j.jbc.2024.108134.

Kinome-wide CRISPR-Cas9 screens revealed as a positive regulator of TGF-β signaling.

Wang D, Zhang X, Guo J, Liu W, Zhou Y, Wang R Biochem Biophys Rep. 2024; 40:101864.

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Network-based elucidation of colon cancer drug resistance mechanisms by phosphoproteomic time-series analysis.

Rosenberger G, Li W, Turunen M, He J, Subramaniam P, Pampou S Nat Commun. 2024; 15(1):3909.

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Role of Post-Translational Modifications in Colorectal Cancer Metastasis.

Peng N, Liu J, Hai S, Liu Y, Zhao H, Liu W Cancers (Basel). 2024; 16(3).

PMID: 38339403 PMC: 10854713. DOI: 10.3390/cancers16030652.

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