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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...

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Autores principales: Otsuka, Kei, Yoshino, Yuki, Qi, Huicheng, Chiba, Natsuko
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
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.
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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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