Critical roles of non-histone protein lysine methylation in human tumorigenesis

Nat Rev Cancer. 2015 Feb;15(2):110-24. doi: 10.1038/nrc3884.


Several protein lysine methyltransferases and demethylases have been identified to have critical roles in histone modification. A large body of evidence has indicated that their dysregulation is involved in the development and progression of various diseases, including cancer, and these enzymes are now considered to be potential therapeutic targets. Although most studies have focused on histone methylation, many reports have revealed that these enzymes also regulate the methylation dynamics of non-histone proteins such as p53, RB1 and STAT3 (signal transducer and activator of transcription 3), which have important roles in human tumorigenesis. In this Review, we summarize the molecular functions of protein lysine methylation and its involvement in human cancer, with a particular focus on lysine methylation of non-histone proteins.

Publication types

  • Review

MeSH terms

  • Cell Transformation, Neoplastic / metabolism*
  • Chromosomal Proteins, Non-Histone / metabolism*
  • Histone-Lysine N-Methyltransferase / metabolism
  • Humans
  • Lysine / metabolism*
  • Methylation
  • Retinoblastoma Protein / metabolism
  • STAT3 Transcription Factor / metabolism
  • Tumor Suppressor Protein p53 / metabolism


  • Chromosomal Proteins, Non-Histone
  • Retinoblastoma Protein
  • STAT3 Transcription Factor
  • STAT3 protein, human
  • Tumor Suppressor Protein p53
  • Histone-Lysine N-Methyltransferase
  • SMYD2 protein, human
  • SMYD3 protein, human
  • Lysine