@article{f37e29a2f8f1476ab3addfb2fc4e3e17,
title = "RACK1 regulates centriole duplication through promoting the activation of polo-like kinase 1 by Aurora A",
abstract = "Breast cancer gene 1 (BRCA1) contributes to the regulation of centrosome number. We previously identified receptor for activated C kinase 1 (RACK1) as a BRCA1-interacting partner. RACK1, a scaffold protein that interacts with multiple proteins through its seven WD40 domains, directly binds to BRCA1 and localizes to centrosomes. RACK1 knockdown suppresses centriole duplication, whereas RACK1 overexpression causes centriole overduplication in a subset of mammary gland-derived cells. In this study, we showed that RACK1 binds directly to polo-like kinase 1 (PLK1) and Aurora A, and promotes the Aurora A–PLK1 interaction. RACK1 knockdown decreased phosphorylated PLK1 (p-PLK1) levels and the centrosomal localization of Aurora A and p-PLK1 in S phase, whereas RACK1 overexpression increased p-PLK1 level and the centrosomal localization of Aurora A and p-PLK1 in interphase, resulting in an increase of cells with abnormal centriole disengagement. Overexpression of cancer-derived RACK1 variants failed to enhance the Aurora A–PLK1 interaction, PLK1 phosphorylation and the centrosomal localization of p-PLK1. These results suggest that RACK1 functions as a scaffold protein that promotes the activation of PLK1 by Aurora A in order to promote centriole duplication.",
keywords = "Aurora A, Cancer, Centriole duplication, Centrosome, PLK1",
author = "Yuki Yoshino and Akihiro Kobayashi and Huicheng Qi and Shino Endo and Zhenzhou Fang and Kazuha Shindo and Ryo Kanazawa and Natsuko Chiba",
note = "Funding Information: This study was supported by grants-in-aid from the Japan Society for the Promotion of Science (JSPS) KAKENHI grant numbers JP16K18409 (to Y.Y.), JP18K15233 (to Y.Y.), JP16H04690 (to N.C. and Y.Y.), JP19H03493 (to N.C. and Y.Y.), the Foundation for Promotion of Cancer Research in Japan, the Sasakawa Scientific Research Grant from The Japan Science Society (to Y.Y.), Friends of Leukemia Research Fund, Research Grant of the Princess Takamatsu Cancer Research Fund, and Research Program of the Smart-Aging Research Center, Tohoku University (to N.C.). Funding Information: We thank Dr Akira Yasui and Dr Ryutaro Shirakawa, Institute of Aging, Development, and Cancer, Tohoku University, for useful suggestions and discussion, and Satoko Kaneko for technical assistance. This study was supported by grants-in-aid from the Japan Society for the Promotion of Science (JSPS) KAKENHI grant numbers JP16K18409 (to Y.Y.), JP18K15233 (to Y.Y.), JP16H04690 (to N.C. and Y.Y.), JP19H03493 (to N.C. and Y.Y.), the Foundation for Promotion of Cancer Research in Japan, the Sasakawa Scientific Research Grant from The Japan Science Society (to Y.Y.), Friends of Leukemia Research Fund, Research Grant of the Princess Takamatsu Cancer Research Fund, and Research Program of the Smart-Aging Research Center, Tohoku University (to N.C.). Publisher Copyright: {\textcopyright} 2020. Published by The Company of Biologists Ltd",
year = "2020",
month = sep,
doi = "10.1242/jcs.238931",
language = "English",
volume = "133",
journal = "Journal of Cell Science",
issn = "0021-9533",
publisher = "Company of Biologists Ltd",
number = "17",
}
