Centre National de la Recherche Scientifique, Unité Mixte de Recherche UMR6290, 35043 Rennes, France.
J Cell Biol. 2012 Apr 2;197(1):19-26. doi: 10.1083/jcb.201107134. Epub 2012 Mar 26.
Aurora A (AurA) is a major mitotic protein kinase involved in centrosome maturation and spindle assembly. Nucleophosmin/B23 (NPM) is a pleiotropic nucleolar protein involved in a variety of cellular processes including centrosome maturation. In the present study, we report that NPM is a strong activator of AurA kinase activity. NPM and AurA coimmunoprecipitate and colocalize to centrosomes in G2 phase, where AurA becomes active. In contrast with previously characterized AurA activators, NPM does not trigger autophosphorylation of AurA on threonine 288. NPM induces phosphorylation of AurA on serine 89, and this phosphorylation is necessary for activation of AurA. These data were confirmed in vivo, as depletion of NPM by ribonucleic acid interference eliminated phosphorylation of CDC25B on S353 at the centrosome, indicating a local loss of AurA activity. Our data demonstrate that NPM is a strong activator of AurA kinase activity at the centrosome and support a novel mechanism of activation for AurA.
极光 A（AurA）是一种主要的有丝分裂蛋白激酶，参与中心体成熟和纺锤体组装。核仁磷酸蛋白/B23（NPM）是一种多功能核仁蛋白，参与多种细胞过程，包括中心体成熟。在本研究中，我们报告 NPM 是 AurA 激酶活性的强激活剂。NPM 和 AurA 共免疫沉淀并共定位到 G2 期的中心体，在该时期 AurA 变得活跃。与先前表征的 AurA 激活剂不同，NPM 不会触发 Thr288 上的 AurA 自身磷酸化。NPM 诱导 AurA 丝氨酸 89 上的磷酸化，并且这种磷酸化对于 AurA 的激活是必需的。这些数据在体内得到了证实，因为 RNA 干扰敲除 NPM 消除了中心体上 CDC25B 上 S353 的磷酸化，表明 AurA 活性的局部丧失。我们的数据表明 NPM 是中心体上 AurA 激酶活性的强激活剂，并支持 AurA 的一种新的激活机制。
