The Function of BARD1 in Centrosome Regulation in Cooperation with BRCA1/OLA1/RACK1
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 majo...
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| Format: | Article |
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MDPI AG
2020-07-01
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| Series: | Genes |
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| Online Access: | https://www.mdpi.com/2073-4425/11/8/842 |
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| author | Kei Otsuka Yuki Yoshino Huicheng Qi Natsuko Chiba |
| author_facet | Kei Otsuka Yuki Yoshino Huicheng Qi Natsuko Chiba |
| author_sort | Kei Otsuka |
| collection | DOAJ |
| description | 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 <i>BRCA1</i> and <i>BARD1</i> 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. |
| first_indexed | 2024-03-10T18:14:41Z |
| format | Article |
| id | doaj.art-231b7b32233048e1b639c260f787fbdf |
| institution | Directory Open Access Journal |
| issn | 2073-4425 |
| language | English |
| last_indexed | 2024-03-10T18:14:41Z |
| publishDate | 2020-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Genes |
| spelling | doaj.art-231b7b32233048e1b639c260f787fbdf2023-11-20T07:47:24ZengMDPI AGGenes2073-44252020-07-0111884210.3390/genes11080842The Function of BARD1 in Centrosome Regulation in Cooperation with BRCA1/OLA1/RACK1Kei Otsuka0Yuki Yoshino1Huicheng Qi2Natsuko Chiba3Department of Cancer Biology, Institute of Development, Aging and Cancer (IDAC), Tohoku University, 4-1 Seiryomachi Aoba-ku, Sendai 980-8575, JapanDepartment of Cancer Biology, Institute of Development, Aging and Cancer (IDAC), Tohoku University, 4-1 Seiryomachi Aoba-ku, Sendai 980-8575, JapanDepartment of Cancer Biology, Institute of Development, Aging and Cancer (IDAC), Tohoku University, 4-1 Seiryomachi Aoba-ku, Sendai 980-8575, JapanDepartment of Cancer Biology, Institute of Development, Aging and Cancer (IDAC), Tohoku University, 4-1 Seiryomachi Aoba-ku, Sendai 980-8575, JapanBreast 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 <i>BRCA1</i> and <i>BARD1</i> 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.https://www.mdpi.com/2073-4425/11/8/842BARD1BRCA1tumor suppressorcentrosomecentriole duplication |
| spellingShingle | Kei Otsuka Yuki Yoshino Huicheng Qi Natsuko Chiba The Function of BARD1 in Centrosome Regulation in Cooperation with BRCA1/OLA1/RACK1 Genes BARD1 BRCA1 tumor suppressor centrosome centriole duplication |
| title | The Function of BARD1 in Centrosome Regulation in Cooperation with BRCA1/OLA1/RACK1 |
| title_full | The Function of BARD1 in Centrosome Regulation in Cooperation with BRCA1/OLA1/RACK1 |
| title_fullStr | The Function of BARD1 in Centrosome Regulation in Cooperation with BRCA1/OLA1/RACK1 |
| title_full_unstemmed | The Function of BARD1 in Centrosome Regulation in Cooperation with BRCA1/OLA1/RACK1 |
| title_short | The Function of BARD1 in Centrosome Regulation in Cooperation with BRCA1/OLA1/RACK1 |
| title_sort | function of bard1 in centrosome regulation in cooperation with brca1 ola1 rack1 |
| topic | BARD1 BRCA1 tumor suppressor centrosome centriole duplication |
| url | https://www.mdpi.com/2073-4425/11/8/842 |
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