RRC ID 68903
Author Wali N, Hosokawa K, Malik S, Saito H, Miyaguchi K, Imajoh-Ohmi S, Miki Y, Nakanishi A.
Title Centrosomal BRCA2 is a target protein of membrane type-1 matrix metalloproteinase (MT1-MMP).
Journal Biochem Biophys Res Commun
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.
Volume 443(4)
Pages 1148-54
Published 2014-1-24
DOI 10.1016/j.bbrc.2013.12.103
PII S0006-291X(13)02174-8
PMID 24384087
MeSH 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
IF 2.985
Human and Animal Cells HeLa.S3