Targeting protein lysine methylation and demethylation in cancers

Acta Biochim Biophys Sin (Shanghai). 2012 Jan;44(1):70-9. doi: 10.1093/abbs/gmr109.


During the last decade, we saw an explosion of studies investigating the role of lysine methylation/demethylation of histones and non-histone proteins, such as p53, NF-kappaB, and E2F1. These 'Ying-Yang' post-translational modifications are important to fine-tuning the activity of these proteins. Lysine methylation and demethylation are catalyzed by protein lysine methyltransferases (PKMTs) and protein lysine demethylases (PKDMs). PKMTs, PKDMs, and their substrates have been shown to play important roles in cancers. Although the underlying mechanisms of tumorigenesis are still largely unknown, growing evidence is starting to link aberrant regulation of methylation to tumorigenesis. This review focuses on summarizing the recent progress in understanding of the function of protein lysine methylation, and in the discovery of small molecule inhibitors for PKMTs and PKDMs. We also discuss the potential and the caveats of targeting protein lysine methylation for the treatment of cancer.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • DNA-Binding Proteins / antagonists & inhibitors
  • Enhancer of Zeste Homolog 2 Protein
  • Enzyme Inhibitors / therapeutic use*
  • Epigenesis, Genetic
  • Histocompatibility Antigens
  • Histone Demethylases / antagonists & inhibitors
  • Histone Demethylases / metabolism*
  • Histone-Lysine N-Methyltransferase / antagonists & inhibitors*
  • Histone-Lysine N-Methyltransferase / metabolism*
  • Humans
  • Jumonji Domain-Containing Histone Demethylases / antagonists & inhibitors
  • Methyltransferases / antagonists & inhibitors
  • Neoplasms / drug therapy*
  • Neoplasms / genetics
  • Polycomb Repressive Complex 2
  • Protein Processing, Post-Translational / drug effects
  • Protein Transport / drug effects
  • Repressor Proteins / antagonists & inhibitors
  • Transcription Factors / antagonists & inhibitors
  • Tumor Suppressor Protein p53 / metabolism


  • DNA-Binding Proteins
  • Enzyme Inhibitors
  • Histocompatibility Antigens
  • KDM4C protein, human
  • Repressor Proteins
  • Transcription Factors
  • Tumor Suppressor Protein p53
  • Histone Demethylases
  • Jumonji Domain-Containing Histone Demethylases
  • KDM1A protein, human
  • SUV39H1 protein, human
  • DOT1L protein, human
  • Methyltransferases
  • EHMT2 protein, human
  • EZH2 protein, human
  • Enhancer of Zeste Homolog 2 Protein
  • Histone-Lysine N-Methyltransferase
  • Polycomb Repressive Complex 2
  • SMYD2 protein, human