TY - JOUR
T1 - The BRCA1/BARD1-Interacting Protein OLA1 Functions in Centrosome Regulation
AU - Matsuzawa, Ayako
AU - Kanno, Shin ichiro
AU - Nakayama, Masahiro
AU - Mochiduki, Hironori
AU - Wei, Leizhen
AU - Shimaoka, Tatsuro
AU - Furukawa, Yumiko
AU - Kato, Kei
AU - Shibata, Shun
AU - Yasui, Akira
AU - Ishioka, Chikashi
AU - Chiba, Natsuko
N1 - Funding Information:
We thank Drs. S. Chiba, M. Ikeda, and K. Mizuno for providing antibody and for helpful discussions. This study was supported by grants-in-aid from the Ministry of Education, Culture, Sports, Science, and Technology, Japan , Project for Development of Innovative Research on Cancer Therapeutics (P-DIRECT); Japan Society for the Promotion of Science ; Japan Science and Technology Agency ; Tohoku University Frontier Research Institute for Interdisciplinary Science ; Takeda Science Foundation ; the Naito Foundation ; Kurokawa Cancer Research Foundation ; Aichi Cancer Research Foundation ; Intelligent Cosmos Academic Foundation ; and Osaka Cancer Research Foundation .
PY - 2014/1/9
Y1 - 2014/1/9
N2 - 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.
AB - 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.
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U2 - 10.1016/j.molcel.2013.10.028
DO - 10.1016/j.molcel.2013.10.028
M3 - Article
C2 - 24289923
AN - SCOPUS:84892186057
SN - 1097-2765
VL - 53
SP - 101
EP - 114
JO - Molecular Cell
JF - Molecular Cell
IS - 1
ER -
