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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...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7464954/ https://www.ncbi.nlm.nih.gov/pubmed/32722046 http://dx.doi.org/10.3390/genes11080842 |
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author | Otsuka, Kei Yoshino, Yuki Qi, Huicheng Chiba, Natsuko |
author_facet | Otsuka, Kei Yoshino, Yuki Qi, Huicheng Chiba, Natsuko |
author_sort | Otsuka, Kei |
collection | PubMed |
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 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. |
format | Online Article Text |
id | pubmed-7464954 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-74649542020-09-04 The Function of BARD1 in Centrosome Regulation in Cooperation with BRCA1/OLA1/RACK1 Otsuka, Kei Yoshino, Yuki Qi, Huicheng Chiba, Natsuko Genes (Basel) Review 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. MDPI 2020-07-24 /pmc/articles/PMC7464954/ /pubmed/32722046 http://dx.doi.org/10.3390/genes11080842 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Review Otsuka, Kei Yoshino, Yuki Qi, Huicheng Chiba, Natsuko The Function of BARD1 in Centrosome Regulation in Cooperation with BRCA1/OLA1/RACK1 |
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 | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7464954/ https://www.ncbi.nlm.nih.gov/pubmed/32722046 http://dx.doi.org/10.3390/genes11080842 |
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