Centrosomal BRCA2 is a target protein of membrane type-1 matrix metalloproteinase (MT1-MMP) |
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| Authors: | Nadila Wali Kana Hosokawa Sadiya Malik Hiroko Saito Ken Miyaguchi Shinobu Imajoh-Ohmi Yoshio Miki Akira Nakanishi |
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| Affiliation: | 1. Department of Molecular Genetics, Medical Research Institute, Tokyo Medical and Dental University (TMDU), Japan;2. Department of Molecular Diagnosis, Cancer Institute, The Japanese Foundation of Cancer Research (JFCR), Japan;3. Medical Proteomics Laboratory, The Institute of Medical Science, The University of Tokyo, Japan;4. Department of Obstetrics and Gynecology, Urumqi Friendship Hospital, Xinjiang, PR China |
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| 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 (2132LSNN/LNVEGG2141), 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. |
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| Keywords: | BRCA2 MT1-MMP Centrosome |
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