PRMTs and Arginine Methylation: Cancer's Best-Kept Secret?

Trends Mol Med. 2019 Nov;25(11):993-1009. doi: 10.1016/j.molmed.2019.05.007. Epub 2019 Jun 20.

Abstract

Post-translational modification (PTM) of proteins is vital for increasing proteome diversity and maintaining cellular homeostasis. If the writing, reading, and removal of modifications are not controlled, cancer can develop. Arginine methylation is an understudied modification that is increasingly associated with cancer progression. Consequently protein arginine methyltransferases (PRMTs), the writers of arginine methylation, have rapidly gained interest as novel drug targets. However, for clinical success a deep mechanistic understanding of the biology of PRMTs is required. In this review we focus on advances made regarding the role of PRMTs in stem cell biology, epigenetics, splicing, immune surveillance and the DNA damage response, and highlight the rapid rise of specific inhibitors that are now in clinical trials for cancer therapy.

Keywords: DNA repair; PRMT; arginine methylation; cancer; cancer stem cells; epigenetic.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology
  • Arginine / metabolism*
  • DNA Damage / drug effects
  • DNA Damage / physiology
  • Drug Resistance / drug effects
  • Epigenomics
  • Histones / metabolism
  • Humans
  • Immunotherapy
  • Methylation*
  • Mice
  • Molecular Targeted Therapy / trends
  • Neoplasms / drug therapy
  • Neoplasms / metabolism*
  • Protein Processing, Post-Translational* / physiology
  • Protein Splicing / drug effects
  • Protein Splicing / physiology
  • Protein-Arginine N-Methyltransferases / metabolism
  • RNA Splicing / drug effects
  • RNA Splicing / physiology
  • Stem Cells / drug effects
  • Stem Cells / physiology

Substances

  • Antineoplastic Agents
  • Histones
  • Arginine
  • Protein-Arginine N-Methyltransferases