title: The BRCA1/BARD1-interacting protein OLA1 functions in centrosome regulation.
abstract: The breast and ovarian cancer-specific tumor suppressor BRCA1, along with its heterodimer partner BRCA1-associated RING domain protein (BARD1), plays important roles in DNA repair, centrosome regulation, and transcription. To explore further functions of BRCA1/BARD1, we performed mass spectrometry analysis and identified Obg-like ATPase 1 (OLA1) as a protein that interacts with the carboxy-terminal region of BARD1. OLA1 directly bound to the amino-terminal region of BRCA1 and γ-tubulin. OLA1 localized to centrosomes in interphase and to the spindle pole in mitotic phase, and its knockdown resulted in centrosome amplification and the activation of microtubule aster formation. OLA1 with a mutation observed in breast cancer cell line, E168Q, failed to bind BRCA1 and rescue the OLA1 knockdown-induced centrosome amplification. BRCA1 variant I42V also abrogated the binding of BRCA1 to OLA1. These findings suggest that OLA1 plays an important role in centrosome regulation together with BRCA1.
authors.affiliation: Department of Molecular Immunology, Institute of Development, Aging, and Cancer (IDAC), Tohoku University, 4-1 Seiryomachi Aoba-ku, Sendai 980-8575, Japan.
authors.forename: Ayako
authors.initials: A
authors.lastname: Matsuzawa
authors.affiliation: Division of Dynamic Proteome in Cancer and Aging, Institute of Development, Aging, and Cancer (IDAC), Tohoku University, 4-1 Seiryomachi Aoba-ku, Sendai 980-8575, Japan.
authors.forename: Shin-Ichiro
authors.initials: S
authors.lastname: Kanno
authors.affiliation: Department of Molecular Immunology, Institute of Development, Aging, and Cancer (IDAC), Tohoku University, 4-1 Seiryomachi Aoba-ku, Sendai 980-8575, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Nakayama
authors.affiliation: Department of Molecular Immunology, Institute of Development, Aging, and Cancer (IDAC), Tohoku University, 4-1 Seiryomachi Aoba-ku, Sendai 980-8575, Japan.
authors.forename: Hironori
authors.initials: H
authors.lastname: Mochiduki
authors.affiliation: Department of Molecular Immunology, Institute of Development, Aging, and Cancer (IDAC), Tohoku University, 4-1 Seiryomachi Aoba-ku, Sendai 980-8575, Japan.
authors.forename: Leizhen
authors.initials: L
authors.lastname: Wei
authors.affiliation: Research Institute for Clinical Oncology, Saitama Cancer Center, 818 Komuro, Ina, Saitama 362-0806, Japan.
authors.forename: Tatsuro
authors.initials: T
authors.lastname: Shimaoka
authors.affiliation: Department of Molecular Immunology, Institute of Development, Aging, and Cancer (IDAC), Tohoku University, 4-1 Seiryomachi Aoba-ku, Sendai 980-8575, Japan.
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Furukawa
authors.affiliation: Department of Molecular Immunology, Institute of Development, Aging, and Cancer (IDAC), Tohoku University, 4-1 Seiryomachi Aoba-ku, Sendai 980-8575, Japan.
authors.forename: Kei
authors.initials: K
authors.lastname: Kato
authors.affiliation: Department of Molecular Immunology, Institute of Development, Aging, and Cancer (IDAC), Tohoku University, 4-1 Seiryomachi Aoba-ku, Sendai 980-8575, Japan.
authors.forename: Shun
authors.initials: S
authors.lastname: Shibata
authors.affiliation: Division of Dynamic Proteome in Cancer and Aging, Institute of Development, Aging, and Cancer (IDAC), Tohoku University, 4-1 Seiryomachi Aoba-ku, Sendai 980-8575, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Yasui
authors.affiliation: Department of Clinical Oncology, Institute of Development, Aging, and Cancer (IDAC), Tohoku University, 4-1 Seiryomachi Aoba-ku, Sendai 980-8575, Japan.
authors.forename: Chikashi
authors.initials: C
authors.lastname: Ishioka
authors.affiliation: Department of Molecular Immunology, Institute of Development, Aging, and Cancer (IDAC), Tohoku University, 4-1 Seiryomachi Aoba-ku, Sendai 980-8575, Japan. Electronic address: nchiba@idac.tohoku.ac.jp.
authors.forename: Natsuko
authors.initials: N
authors.lastname: Chiba
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics / Q000378:metabolism*; D019943:Amino Acid Substitution; D019313:BRCA1 Protein / Q000235:genetics / Q000378:metabolism*; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D018385:Centrosome / Q000378:metabolism*; D005260:Female; D019204:GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D055785:Gene Knockdown Techniques; D006801:Humans; D020125:Mutation, Missense; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism
chemical_list: D019313:BRCA1 Protein; C492913:BRCA1 protein, human; D025521:Tumor Suppressor Proteins; C102449:BARD1 protein, human; D044767:Ubiquitin-Protein Ligases; D000251:Adenosine Triphosphatases; D019204:GTP-Binding Proteins; C522732:OLA1 protein, human