Centrosomal BRCA2 is a target protein of membrane type-1 matrix metalloproteinase (MT1-MMP)

Biochem Biophys Res Commun. 2014 Jan 24;443(4):1148-54. doi: 10.1016/j.bbrc.2013.12.103. Epub 2013 Dec 30.

Abstract

BRCA2 localizes to centrosomes between G1 and prophase and is removed from the centrosomes during mitosis, but the underlying mechanism is not clear. Here we show that BRCA2 is cleaved into two fragments by membrane type-1 matrix metalloproteinase (MT1-MMP), and that knockdown of MT1-MMP prevents the removal of BRCA2 from centrosomes during metaphase. Mass spectrometry mapping revealed that the MT1-MMP cleavage site of human BRCA2 is between Asn-2135 and Leu-2136 ((2132)LSNN/LNVEGG(2141)), and the point mutation L2136D abrogated MT1-MMP cleavage. Our data demonstrate that MT1-MMP proteolysis of BRCA2 regulates the abundance of BRCA2 on centrosomes.

Keywords: BRCA2; Centrosome; MT1-MMP.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Amino Acid Substitution
  • BRCA2 Protein / chemistry
  • BRCA2 Protein / genetics
  • BRCA2 Protein / metabolism*
  • Binding Sites / genetics
  • Cell Cycle
  • Cell Division
  • Centrosome / metabolism*
  • Gene Knockdown Techniques
  • HeLa Cells
  • Humans
  • Matrix Metalloproteinase 14 / genetics
  • Matrix Metalloproteinase 14 / metabolism*
  • Molecular Sequence Data
  • Mutagenesis, Site-Directed
  • Recombinant Fusion Proteins / chemistry
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism

Substances

  • BRCA2 Protein
  • BRCA2 protein, human
  • Recombinant Fusion Proteins
  • MMP14 protein, human
  • Matrix Metalloproteinase 14