Nucleophosmin/B23 activates Aurora A at the centrosome through phosphorylation of serine 89
Nucleophosmin/B23 activates Aurora A at the centrosome through phosphorylation of serine 89
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DOI：
10.1083/jcb.201107134
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发表时间：
2012-04-02
影响因子：
7.8
通讯作者：
Prigent, Claude
中科院分区：
文献类型：
--
作者：
Reboutier, David;Troadec, Marie-Berengere;Prigent, Claude
Aurora A（AurA）是一种重要的有丝分裂蛋白激酶，参与中心体成熟和纺锤体组装。核磷酸蛋白/B23（NPM）是一种多效核仁蛋白，参与包括中心体成熟在内的多种细胞过程。在本研究中，我们报告说，NPM是一个强大的激活剂的AurA激酶活性。NPM和AurA在G2期共免疫沉淀并共定位于中心体，此时AurA变得活跃。与先前表征的AurA激活剂相比，NPM不会触发AurA在苏氨酸288上的自磷酸化。NPM诱导AurA在丝氨酸89上的磷酸化，并且这种磷酸化对于AurA的活化是必需的。这些数据在体内得到了证实，因为通过核糖核酸干扰消除NPM消除了中心体S353上CDC 25 B的磷酸化，表明AurA活性的局部丧失。我们的数据表明，NPM是一个强大的激活剂的AurA激酶活性的中心体，并支持一种新的机制激活AurA。
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.