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Published on: November 11, 2022
Aurora A polyubiquitinates the BRCA1-interacting protein OLA1 to promote centrosome maturation
Zhenzhou Fang1, Xingming Li2, Yuki Yoshino3
1Department 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.
Abstract:
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.
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