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
|
Resource |
Human and Animal Cells |
HeLa.S3 |