UTX Mutations in Human Cancer

Cancer Cell. 2019 Feb 11;35(2):168-176. doi: 10.1016/j.ccell.2019.01.001.

Abstract

Ubiquitously transcribed tetratricopeptide repeat on chromosome X (UTX, encoded by KDM6A) is a histone demethylase that targets di- and tri-methylated histone H3 lysine 27 (H3K27). UTX function has been linked to homeotic gene expression, embryonic development, and cellular reprogramming. UTX and its protein interactors within the COMPASS family, including the MLL3 and MLL4 lysine methyltransferases, are frequently mutated in multiple human cancers; however, the molecular basis of how these mutations contribute to oncogenesis remains unclear. Here, we discuss catalytic-dependent and -independent functions of UTX and its partners MLL3 and MLL4 as part of the COMPASS family during development and in oncogenesis.

Keywords: UTX; cancer; chromatin; gene expression; transcription.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • Demethylation
  • Gene Expression Regulation, Neoplastic
  • Genetic Predisposition to Disease
  • Histone Demethylases / genetics*
  • Histone Demethylases / metabolism
  • Histone-Lysine N-Methyltransferase
  • Histones / metabolism
  • Humans
  • Mutation*
  • Neoplasms / enzymology
  • Neoplasms / genetics*
  • Neoplasms / pathology
  • Phenotype
  • Signal Transduction
  • Tumor Suppressor Proteins / genetics*
  • Tumor Suppressor Proteins / metabolism

Substances

  • DNA-Binding Proteins
  • Histones
  • KMT2C protein, human
  • Tumor Suppressor Proteins
  • Histone Demethylases
  • KDM6A protein, human
  • Histone-Lysine N-Methyltransferase
  • MLL4 protein, human