Review Article

Post-translational modification of KRAS: potential targets for cancer therapy

Wei-hua Wang1, Tao Yuan1, Mei-jia Qian1, Fang-jie Yan1, Liu Yang2, Qiao-jun He1, Bo Yang1, Jin-jian Lu3, Hong Zhu1
1 Zhejiang Province Key Laboratory of Anti-cancer Drug Research, Institute of Pharmacology and Toxicology, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China
2 Key Laboratory of Tumor Molecular Diagnosis and Individualized Medicine of Zhejiang Province, Zhejiang Provincial People’s Hospital, People’s Hospital of Hangzhou Medical College, Hangzhou 310014, China
3 State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao, China
Correspondence to: Jin-jian Lu: jinjianlu@um.edu.mo, Hong Zhu: hongzhu@zju.edu.cn,
DOI: 10.1038/s41401-020-00542-y
Received: 5 July 2020
Accepted: 16 September 2020
Advance online: 21 October 2020

Abstract

Aberrant activation of the RAS superfamily is one of the critical factors in carcinogenesis. Among them, KRAS is the most frequently mutated one which has inspired extensive studies for developing approaches to intervention. Although the cognition toward KRAS remains far from complete, mounting evidence suggests that a variety of post-translational modifications regulate its activation and localization. In this review, we summarize the regulatory mode of post-translational modifications on KRAS including prenylation, post-prenylation, palmitoylation, ubiquitination, phosphorylation, SUMOylation, acetylation, nitrosylation, etc. We also highlight the recent studies targeting these modifications having exhibited potent anti-tumor activities.
Keywords: oncogene; KRAS; post-translational modification; prenylation; postprenylation; palmitoylation; ubiquitination; phosphorylation; SUMOylation; acetylation; nitrosylation; cancer therapy

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