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Mol Cell. 2014 Jan 9;53(1):101-14. doi: 10.1016/j.molcel.2013.10.028. Epub 2013 Nov 27.

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

Author information

1
Department of Molecular Immunology, Institute of Development, Aging, and Cancer (IDAC), Tohoku University, 4-1 Seiryomachi Aoba-ku, Sendai 980-8575, Japan.
2
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.
3
Research Institute for Clinical Oncology, Saitama Cancer Center, 818 Komuro, Ina, Saitama 362-0806, Japan.
4
Department of Clinical Oncology, Institute of Development, Aging, and Cancer (IDAC), Tohoku University, 4-1 Seiryomachi Aoba-ku, Sendai 980-8575, Japan.
5
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.

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.

PMID:
24289923
DOI:
10.1016/j.molcel.2013.10.028
[Indexed for MEDLINE]
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