极光 A 通过多泛素化 BRCA1 相互作用蛋白 OLA1 来促进中心体成熟。
Aurora A polyubiquitinates the BRCA1-interacting protein OLA1 to promote centrosome maturation.
机构信息
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.
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.
出版信息
Cell Rep. 2023 Aug 29;42(8):112850. doi: 10.1016/j.celrep.2023.112850. Epub 2023 Jul 21.
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.
BRCA1 相互作用蛋白 Obg 样 ATP 酶 1（OLA1）在中心体复制中发挥作用。在这项研究中，我们展示了有丝分裂激酶 Aurora A 在减少中心体 OLA1 中的作用。Aurora A 与 OLA1 结合并使其多泛素化，将其靶向蛋白酶体降解。NIMA 相关激酶 2（NEK2）磷酸化 OLA1 的 T124 残基，增加 OLA1 与 Aurora A 的结合以及 Aurora A 对 OLA1 的多泛素化，并减少 G2 期中心体的 OLA1。Aurora A 的激酶活性抑制 OLA1 多泛素化。Aurora A 介导的多泛素化引起的中心体 OLA1 减少促进了 G2 期中心粒周围物质蛋白的募集。Aurora A 的 E3 连接酶活性对于其过表达诱导的中心体扩增至关重要。结果表明 Aurora A 作为 E3 泛素连接酶和激酶在调节中心体 OLA1 中的双重功能，这对于 G2 期中心体的正常成熟至关重要。
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