{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,4]],"date-time":"2026-07-04T00:25:58Z","timestamp":1783124758575,"version":"3.54.6"},"reference-count":98,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2020,7,24]],"date-time":"2020-07-24T00:00:00Z","timestamp":1595548800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"JSPS KAKENHI","award":["JP19K18020, JP18K15233, JP19H03493"],"award-info":[{"award-number":["JP19K18020, JP18K15233, JP19H03493"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Breast cancer gene 1 (BRCA1)-associated RING domain protein 1 (BARD1) forms a heterodimer with BRCA1, a tumor suppressor associated with hereditary breast and ovarian cancer. BRCA1\/BARD1 functions in multiple cellular processes including DNA repair and centrosome regulation. Centrosomes are the major microtubule-organizing centers in animal cells and are critical for the formation of a bipolar mitotic spindle. BRCA1 and BARD1 localize to the centrosome during the cell cycle, and the BRCA1\/BARD1 dimer ubiquitinates centrosomal proteins to regulate centrosome function. We identified Obg-like ATPase 1 (OLA1) and receptor for activated C kinase (RACK1) as BRCA1\/BARD1-interating proteins that bind to BARD1 and BRCA1 and localize the centrosomes during the cell cycle. Cancer-derived variants of BRCA1, BARD1, OLA1, and RACK1 failed to interact, and aberrant expression of these proteins caused centrosome amplification due to centriole overduplication only in mammary tissue-derived cells. In S-G2 phase, the number of centrioles was higher in mammary tissue-derived cells than in cells from other tissues, suggesting their involvement in tissue-specific carcinogenesis by BRCA1 and BARD1 germline mutations. We described the function of BARD1 in centrosome regulation in cooperation with BRCA1\/OLA1\/RACK1, as well as the effect of their dysfunction on carcinogenesis.<\/jats:p>","DOI":"10.3390\/genes11080842","type":"journal-article","created":{"date-parts":[[2020,7,24]],"date-time":"2020-07-24T09:06:09Z","timestamp":1595581569000},"page":"842","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["The Function of BARD1 in Centrosome Regulation in Cooperation with BRCA1\/OLA1\/RACK1"],"prefix":"10.3390","volume":"11","author":[{"given":"Kei","family":"Otsuka","sequence":"first","affiliation":[{"name":"Department of Cancer Biology, Institute of Development, Aging and Cancer (IDAC), Tohoku University, 4-1 Seiryomachi Aoba-ku, Sendai 980-8575, Japan"},{"name":"Laboratory of Cancer Biology, Graduate School of Life Sciences, Tohoku University, 4-1 Seiryomachi Aoba-ku, Sendai 980-8575, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuki","family":"Yoshino","sequence":"additional","affiliation":[{"name":"Department of Cancer Biology, Institute of Development, Aging and Cancer (IDAC), Tohoku University, 4-1 Seiryomachi Aoba-ku, Sendai 980-8575, Japan"},{"name":"Laboratory of Cancer Biology, Graduate School of Life Sciences, Tohoku University, 4-1 Seiryomachi Aoba-ku, Sendai 980-8575, Japan"},{"name":"Department of Cancer Biology, Tohoku University Graduate School of Medicine, 4-1 Seiryomachi Aoba-ku, Sendai 980-8575, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huicheng","family":"Qi","sequence":"additional","affiliation":[{"name":"Department of Cancer Biology, Institute of Development, Aging and Cancer (IDAC), Tohoku University, 4-1 Seiryomachi Aoba-ku, Sendai 980-8575, Japan"},{"name":"Department of Cancer Biology, Tohoku University Graduate School of Medicine, 4-1 Seiryomachi Aoba-ku, Sendai 980-8575, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6504-1290","authenticated-orcid":false,"given":"Natsuko","family":"Chiba","sequence":"additional","affiliation":[{"name":"Department of Cancer Biology, Institute of Development, Aging and Cancer (IDAC), Tohoku University, 4-1 Seiryomachi Aoba-ku, Sendai 980-8575, Japan"},{"name":"Laboratory of Cancer Biology, Graduate School of Life Sciences, Tohoku University, 4-1 Seiryomachi Aoba-ku, Sendai 980-8575, Japan"},{"name":"Department of Cancer Biology, Tohoku University Graduate School of Medicine, 4-1 Seiryomachi Aoba-ku, Sendai 980-8575, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,7,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1126\/science.7545954","article-title":"A strong candidate for the breast and ovarian cancer susceptibility gene BRCA1","volume":"266","author":"Miki","year":"1994","journal-title":"Science"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1329","DOI":"10.1200\/JCO.2006.09.1066","article-title":"Meta-analysis of BRCA1 and BRCA2 penetrance","volume":"25","author":"Chen","year":"2007","journal-title":"J. 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