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

被引:32
|
作者
Wang, Wei-hua [1 ]
Yuan, Tao [1 ]
Qian, Mei-jia [1 ]
Yan, Fang-jie [1 ]
Yang, Liu [2 ]
He, Qiao-jun [1 ]
Yang, Bo [1 ]
Lu, Jin-jian [3 ]
Zhu, Hong [1 ]
机构
[1] Zhejiang Univ, Inst Pharmacol & Toxicol, Coll Pharmaceut Sci, Zhejiang Prov Key Lab Anticanc Drug Res, Hangzhou 310058, Peoples R China
[2] Zhejiang Prov Peoples Hosp, Peoples Hosp, Hangzhou Med Coll, Key Lab Tumor Mol Diag & Individualized Med Zheji, Hangzhou 310014, Peoples R China
[3] Univ Macau, Inst Chinese Med Sci, State Key Lab Qual Res Chinese Med, Macau, Peoples R China
关键词
oncogene; KRAS; post-translational modification; prenylation; postprenylation; palmitoylation; ubiquitination; phosphorylation; SUMOylation; acetylation; nitrosylation; cancer therapy; GUANINE-NUCLEOTIDE EXCHANGE; SMALL-MOLECULE INHIBITOR; ONCOGENIC K-RAS; ZOLEDRONIC ACID; CELL-GROWTH; H-RAS; PROTEIN PALMITOYLATION; MEMBRANE LOCALIZATION; ELECTROSTATIC SWITCH; SIGNAL-TRANSDUCTION;
D O I
10.1038/s41401-020-00542-y
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
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.
引用
收藏
页码:1201 / 1211
页数:11
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