Journal
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
Volume 443, Issue 4, Pages 1148-1154Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2013.12.103
Keywords
BRCA2; MT1-MMP; Centrosome
Categories
Funding
- JSPS KAKENHI Grant [23650592]
- Grants-in-Aid for Scientific Research [25640061, 23650592] Funding Source: KAKEN
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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 ((LSNN)-L-2132/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. (C) 2013 Elsevier Inc. All rights reserved.
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