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

Acta Pharmacol Sin. 2021 Aug;42(8):1201-1211. doi: 10.1038/s41401-020-00542-y. Epub 2020 Oct 21.

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: KRAS; SUMOylation; acetylation; cancer therapy; nitrosylation; oncogene; palmitoylation; phosphorylation; post-translational modification; postprenylation; prenylation; ubiquitination.

Publication types

  • Review

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Humans
  • Protein Processing, Post-Translational / drug effects
  • Protein Processing, Post-Translational / physiology*
  • Proto-Oncogene Proteins p21(ras) / metabolism*

Substances

  • KRAS protein, human
  • Proto-Oncogene Proteins p21(ras)