TY - JOUR
T1 - The function of BARD1 in centrosome regulation in cooperation with BRCA1/OLA1/RACK1
AU - Otsuka, Kei
AU - Yoshino, Yuki
AU - Qi, Huicheng
AU - Chiba, Natsuko
N1 - Funding Information:
Funding: This study was supported by grants-in-aid from JSPS KAKENHI Grant Numbers JP19K18020 (to K. Otsuka), JP18K15233 (to Y. Yoshino), JP19H03493 (to N. Chiba, K. Otsuka, and Y. Yoshino); Research Grant of the Princess Takamatsu Cancer Research Fund (to N. Chiba); and Research Program of the Smart-Aging Research Center, Tohoku University (to N. Chiba).
Publisher Copyright:
© 2020 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2020/8
Y1 - 2020/8
N2 - 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.
AB - 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.
KW - BARD1
KW - BRCA1
KW - Centriole duplication
KW - Centrosome
KW - Tumor suppressor
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U2 - 10.3390/genes11080842
DO - 10.3390/genes11080842
M3 - Review article
C2 - 32722046
AN - SCOPUS:85088811804
SN - 2073-4425
VL - 11
SP - 1
EP - 13
JO - Genes
JF - Genes
IS - 8
M1 - 842
ER -
