title: Centrosomal BRCA2 is a target protein of membrane type-1 matrix metalloproteinase (MT1-MMP).
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.
authors.affiliation: Department of Molecular Genetics, Medical Research Institute, Tokyo Medical and Dental University (TMDU), Japan; Department of Obstetrics and Gynecology, Urumqi Friendship Hospital, Xinjiang, PR China.
authors.forename: Nadila
authors.initials: N
authors.lastname: Wali
authors.affiliation: Department of Molecular Genetics, Medical Research Institute, Tokyo Medical and Dental University (TMDU), Japan.
authors.forename: Kana
authors.initials: K
authors.lastname: Hosokawa
authors.affiliation: Department of Molecular Genetics, Medical Research Institute, Tokyo Medical and Dental University (TMDU), Japan.
authors.forename: Sadiya
authors.initials: S
authors.lastname: Malik
authors.affiliation: Department of Molecular Diagnosis, Cancer Institute, The Japanese Foundation of Cancer Research (JFCR), Japan.
authors.forename: Hiroko
authors.initials: H
authors.lastname: Saito
authors.affiliation: Department of Molecular Genetics, Medical Research Institute, Tokyo Medical and Dental University (TMDU), Japan.
authors.forename: Ken
authors.initials: K
authors.lastname: Miyaguchi
authors.affiliation: Medical Proteomics Laboratory, The Institute of Medical Science, The University of Tokyo, Japan.
authors.forename: Shinobu
authors.initials: S
authors.lastname: Imajoh-Ohmi
authors.affiliation: Department of Molecular Genetics, Medical Research Institute, Tokyo Medical and Dental University (TMDU), Japan; Department of Molecular Diagnosis, Cancer Institute, The Japanese Foundation of Cancer Research (JFCR), Japan. Electronic address: miki.mgen@mri.tmd.ac.jp.
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Miki
authors.affiliation: Department of Molecular Genetics, Medical Research Institute, Tokyo Medical and Dental University (TMDU), Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Nakanishi
mesh_terms: D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D024682:BRCA2 Protein / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D001665:Binding Sites / Q000235:genetics; D002453:Cell Cycle; D002455:Cell Division; D018385:Centrosome / Q000378:metabolism*; D055785:Gene Knockdown Techniques; D006367:HeLa Cells; D006801:Humans; D053511:Matrix Metalloproteinase 14 / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism
chemical_list: D024682:BRCA2 Protein; C551750:BRCA2 protein, human; D011993:Recombinant Fusion Proteins; C507086:MMP14 protein, human; D053511:Matrix Metalloproteinase 14
keywords: BRCA2; Centrosome; MT1-MMP