New concepts on BARD1: Regulator of BRCA pathways and beyond

Int J Biochem Cell Biol. 2016 Mar;72:1-17. doi: 10.1016/j.biocel.2015.12.008. Epub 2015 Dec 29.

Abstract

For nearly two decades most research on BARD1 was closely linked to research on BRCA1, the breast cancer predisposition gene. The co-expression of BARD1 and BRCA1 genes in most tissues, the nearly identical phenotype of Bard1 and Brca1 knock-out mice, and the fact that BRCA1 and BARD1 proteins form a stable complex, led to the general assumption that BARD1 acts as an accessory to BRCA1. More recent research on both proteins showed that BRCA1 and BARD1 might have common as well as separate functions. This review is an overview of how BARD1 functions and controls BRCA1. It highlights also experimental evidence for dominant negative, tumor promoting, functions of aberrant isoforms of BARD1 that are associated with and drivers of various types of cancer.

Keywords: Alternative splicing; Cancer biomarker; Cancer predisposition; Cancer treatment; Competing endogenous RNA.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Animals
  • BRCA1 Protein / metabolism*
  • Epigenesis, Genetic
  • Humans
  • Molecular Sequence Data
  • Neoplasms / genetics
  • Neoplasms / metabolism
  • Neoplasms / pathology
  • Neoplasms / therapy
  • Phenotype
  • Protein Isoforms / chemistry
  • Protein Isoforms / deficiency
  • Protein Isoforms / genetics
  • Protein Isoforms / metabolism
  • Tumor Suppressor Proteins / chemistry
  • Tumor Suppressor Proteins / deficiency
  • Tumor Suppressor Proteins / genetics
  • Tumor Suppressor Proteins / metabolism*

Substances

  • BRCA1 Protein
  • Protein Isoforms
  • Tumor Suppressor Proteins