Home » Key Scientific Articles » The BRCA1/BARD1-interacting protein OLA1 functions in centrosome regulation

The BRCA1/BARD1-interacting protein OLA1 functions in centrosome regulation

Matsuzawa A, Kanno S, Nakayama M, Mochiduki H, Wei L, Shimaoka T, Furukawa Y, Kato K, Shibata S, Yasui A, Ishioka C, Chiba N.

Mol Cell. 2014 Jan 9;53(1):101-14.

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 and

Research Institute for Clinical Oncology, Saitama Cancer Center, 818 Komuro, Ina, Saitama 362-0806, Japan and

Department of Clinical Oncology, Institute of Development, Aging, and Cancer (IDAC), Tohoku University, 4-1 Seiryomachi Aoba-ku, Sendai 980-8575, Japan and

Department of Molecular Immunology, Institute of Development, Aging, and Cancer (IDAC), Tohoku University, 4-1 Seiryomachi Aoba-ku, Sendai 980-8575, Japan. Electronic address: [email protected]

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 {Gamma}-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.

Copyright © 2014 Elsevier Inc. All rights reserved.

Go To PubMed

 

BRCA1/BARD1-interacting protein OLA1 functions in centrosome regulation. Global Medical Discovery