Stress-dependent nucleolin mobilization mediated by p53-nucleolin complex formation
Stress-dependent nucleolin mobilization mediated by p53-nucleolin complex formation
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DOI：
10.1128/mcb.22.16.6014-6022.2002
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发表时间：
2002-08-01
影响因子：
5.3
通讯作者：
Borowiec, JA
中科院分区：
文献类型：
--
作者：
Daniely, Y;Dimitrova, DD;Borowiec, JA
我们最近发现，热休克导致核蛋白从核仁重新定位到核质，从而与复制蛋白A结合并抑制DNA复制起始。我们报道核蛋白动员也发生在暴露于电离辐射（IR）和喜树碱治疗后。动员是选择性的，因为另一种核仁标记物，上游结合因子，不会响应IR重新定位。核蛋白的再定位依赖于p53和应激，后者最初刺激核蛋白-p53复合物的形成。体内核蛋白的再定位和复合体的形成不依赖于p53的转激活，但需要p53的c端调控结构域。核仁蛋白和p53在体外也直接相互作用，对p53结构域有类似的要求。这些数据表明了一种新的p53依赖机制，在这种机制中，细胞应激动员核蛋白进行短暂的复制抑制和DNA修复。
We recently discovered that heat shock causes nucleolin to relocalize from the nucleolus to the nucleoplasm, whereupon it binds replication protein A and inhibits DNA replication initiation. We report that nucleolin mobilization also occurs following exposure to ionizing radiation (IR) and treatment with camptothecin. Mobilization was selective in that another nucleolar marker, upstream binding factor, did not relocalize in response to IR. Nucleolin relocalization was dependent on p53 and stress, the latter initially stimulating nucleolin-p53 complex formation. Nucleolin relocalization and complex formation in vivo were independent of p53 transactivation but required the p53 C-terminal regulatory domain. Nucleolin and p53 also interact directly in vitro, with a similar requirement for p53 domains. These data indicate a novel p53-dependent mechanism in which cell stress mobilizes nucleolin for transient replication inhibition and DNA repair.