Functions of bromodomain-containing proteins and their roles in homeostasis and cancer

Nat Rev Mol Cell Biol. 2017 Apr;18(4):246-262. doi: 10.1038/nrm.2016.143. Epub 2017 Jan 5.

Abstract

Bromodomains (BRDs) are evolutionarily conserved protein-protein interaction modules that are found in a wide range of proteins with diverse catalytic and scaffolding functions and are present in most tissues. BRDs selectively recognize and bind to acetylated Lys residues - particularly in histones - and thereby have important roles in the regulation of gene expression. BRD-containing proteins are frequently dysregulated in cancer, they participate in gene fusions that generate diverse, frequently oncogenic proteins, and many cancer-causing mutations have been mapped to the BRDs themselves. Importantly, BRDs can be targeted by small-molecule inhibitors, which has stimulated many translational research projects that seek to attenuate the aberrant functions of BRD-containing proteins in disease.

Publication types

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

MeSH terms

  • Acylation
  • Animals
  • Chromatin Assembly and Disassembly
  • Gene Expression Regulation*
  • Histones / metabolism
  • Homeostasis
  • Humans
  • Lysine / metabolism
  • Mutation
  • Neoplasms / genetics
  • Neoplasms / metabolism*
  • Oncogene Proteins, Fusion / chemistry
  • Oncogene Proteins, Fusion / metabolism
  • Protein Domains
  • Protein Processing, Post-Translational
  • Proteins / chemistry*
  • Proteins / genetics
  • Proteins / metabolism*
  • Tumor Suppressor Proteins / genetics
  • Tumor Suppressor Proteins / metabolism

Substances

  • Histones
  • Oncogene Proteins, Fusion
  • Proteins
  • Tumor Suppressor Proteins
  • Lysine