Aurora A polyubiquitinates the BRCA1-interacting protein OLA1 to promote centrosome maturation
Zhenzhou Fang,
Xingming Li,
Yuki Yoshino,
Moe Suzuki,
Huicheng Qi,
Hinari Murooka,
Riko Katakai,
Matsuyuki Shirota,
Thi Anh Mai Pham,
Ayako Matsuzawa,
Kei Otsuka,
Chikashi Ishioka,
Takahiro Mori,
Natsuko Chiba
Affiliations
Zhenzhou Fang
Department of Cancer Biology, Institute of Development, Aging and Cancer (IDAC), Tohoku University, 4-1 Seiryomachi Aoba-ku, Sendai 980-8575, Japan; Department of Cancer Biology, Tohoku University Graduate School of Medicine, 4-1 Seiryomachi Aoba-ku, Sendai 980-8575, Japan
Xingming Li
Department of Cancer Biology, Institute of Development, Aging and Cancer (IDAC), Tohoku University, 4-1 Seiryomachi Aoba-ku, Sendai 980-8575, Japan; Laboratory of Cancer Biology, Graduate School of Life Sciences, Tohoku University, 4-1 Seiryomachi Aoba-ku, Sendai 980-8575, Japan
Yuki Yoshino
Department of Cancer Biology, Institute of Development, Aging and Cancer (IDAC), Tohoku University, 4-1 Seiryomachi Aoba-ku, Sendai 980-8575, Japan; Department of Cancer Biology, Tohoku University Graduate School of Medicine, 4-1 Seiryomachi Aoba-ku, Sendai 980-8575, Japan; Laboratory of Cancer Biology, Graduate School of Life Sciences, Tohoku University, 4-1 Seiryomachi Aoba-ku, Sendai 980-8575, Japan
Moe Suzuki
Department of Cancer Biology, Institute of Development, Aging and Cancer (IDAC), Tohoku University, 4-1 Seiryomachi Aoba-ku, Sendai 980-8575, Japan; Laboratory of Cancer Biology, Graduate School of Life Sciences, Tohoku University, 4-1 Seiryomachi Aoba-ku, Sendai 980-8575, Japan
Huicheng Qi
Department of Cancer Biology, Institute of Development, Aging and Cancer (IDAC), Tohoku University, 4-1 Seiryomachi Aoba-ku, Sendai 980-8575, Japan; Department of Cancer Biology, Tohoku University Graduate School of Medicine, 4-1 Seiryomachi Aoba-ku, Sendai 980-8575, Japan
Hinari Murooka
Department of Cancer Biology, Institute of Development, Aging and Cancer (IDAC), Tohoku University, 4-1 Seiryomachi Aoba-ku, Sendai 980-8575, Japan; Laboratory of Cancer Biology, Graduate School of Life Sciences, Tohoku University, 4-1 Seiryomachi Aoba-ku, Sendai 980-8575, Japan
Riko Katakai
Department of Cancer Biology, Institute of Development, Aging and Cancer (IDAC), Tohoku University, 4-1 Seiryomachi Aoba-ku, Sendai 980-8575, Japan; Laboratory of Cancer Biology, Graduate School of Life Sciences, Tohoku University, 4-1 Seiryomachi Aoba-ku, Sendai 980-8575, Japan
Matsuyuki Shirota
Division of Interdisciplinary Medical Science, Tohoku University Graduate School of Medicine, 2-1 Seiryomachi Aoba-ku, Sendai 980-8575, Japan
Thi Anh Mai Pham
Department of Cancer Biology, Institute of Development, Aging and Cancer (IDAC), Tohoku University, 4-1 Seiryomachi Aoba-ku, Sendai 980-8575, Japan; Laboratory of Cancer Biology, Graduate School of Life Sciences, Tohoku University, 4-1 Seiryomachi Aoba-ku, Sendai 980-8575, Japan
Ayako Matsuzawa
Department of Molecular Immunology, Institute of Development, Aging and Cancer (IDAC), Tohoku University, 4-1 Seiryomachi Aoba-ku, Sendai 980-8575, Japan
Kei Otsuka
Department of Cancer Biology, Institute of Development, Aging and Cancer (IDAC), Tohoku University, 4-1 Seiryomachi Aoba-ku, Sendai 980-8575, Japan; Laboratory of Cancer Biology, Graduate School of Life Sciences, Tohoku University, 4-1 Seiryomachi Aoba-ku, Sendai 980-8575, Japan
Chikashi Ishioka
Department of Clinical Oncology, Tohoku University Graduate School of Medicine, 4-1 Seiryomachi Aoba-ku, Sendai 980-8575, Japan
Takahiro Mori
Department of Clinical Oncology, Tohoku University Graduate School of Medicine, 4-1 Seiryomachi Aoba-ku, Sendai 980-8575, Japan; Departemt of Medical Oncology and Hematology, Okinawa Chubu Hospital, 281 Miyazato, Uruma, Okinawa 904-2293, Japan; Genome Medical Science Project, National Center for Global Health and Medicine, 1-21-1 Toyama, Shinjuku, Tokyo 162-8655, Japan
Natsuko Chiba
Department of Cancer Biology, Institute of Development, Aging and Cancer (IDAC), Tohoku University, 4-1 Seiryomachi Aoba-ku, Sendai 980-8575, Japan; Department of Cancer Biology, Tohoku University Graduate School of Medicine, 4-1 Seiryomachi Aoba-ku, Sendai 980-8575, Japan; Laboratory of Cancer Biology, Graduate School of Life Sciences, Tohoku University, 4-1 Seiryomachi Aoba-ku, Sendai 980-8575, Japan; Corresponding author
Summary: The BRCA1-interacting protein Obg-like ATPase 1 (OLA1) functions in centriole duplication. In this study, we show the role of the mitotic kinase Aurora A in the reduction of centrosomal OLA1. Aurora A binds to and polyubiquitinates OLA1, targeting it for proteasomal degradation. NIMA-related kinase 2 (NEK2) phosphorylates the T124 residue of OLA1, increases binding of OLA1 to Aurora A and OLA1 polyubiquitination by Aurora A, and reduces centrosomal OLA1 in G2 phase. The kinase activity of Aurora A suppresses OLA1 polyubiquitination. The decrease in centrosomal OLA1 caused by Aurora A-mediated polyubiquitination promotes the recruitment of pericentriolar material proteins in G2 phase. The E3 ligase activity of Aurora A is critical for centrosome amplification induced by its overexpression. The results suggest a dual function of Aurora A as an E3 ubiquitin ligase and a kinase in the regulation of centrosomal OLA1, which is essential for proper centrosome maturation in G2 phase.
