CEP70 Protein Interacts with γ-Tubulin to Localize at the Centrosome and Is Critical for Mitotic Spindle Assembly
CEP70 Protein Interacts with γ-Tubulin to Localize at the Centrosome and Is Critical for Mitotic Spindle Assembly
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DOI：
10.1074/jbc.m111.252262
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发表时间：
2011-09-23
影响因子：
4.8
通讯作者：
Zhou, Jun
中科院分区：
文献类型：
--
作者：
Shi, Xingjuan;Sun, Xiaoou;Zhou, Jun
有丝分裂纺锤体的失控与基因组不稳定有关，基因组不稳定是肿瘤发生和恶变的一个重要方面。为了确保染色体传递的保真度，有丝分裂纺锤体通过精密的机制组装在动物细胞中，并由中心体协调。中心体蛋白尤其被认为是协调作用，以确保准确的纺锤体形成，但分子细节仍有待研究。在这项研究中，我们报道了一种新的中心体蛋白Cep70的分子特征和功能分析。我们的数据表明，Cep70在整个细胞周期中定位于中心体，并通过包含卷曲结构域的多肽片段与关键的中心体成分-微管蛋白结合。我们的数据进一步揭示了Cep70的中心体定位模式依赖于它与γ-微管蛋白的相互作用。值得注意的是，Cep70在间期细胞中预先存在的和新生的微管的组织中都发挥着重要的作用。此外，Cep70是有丝分裂过程中双极纺锤体的组织和定位所必需的。因此，这些结果首次报告了Cep70是一种重要的中心体蛋白，它与γ-微管蛋白相互作用，并强调了它在有丝分裂纺锤体组装调节中的关键作用。
Deregulation of the mitotic spindle has been implicated in genomic instability, an important aspect of tumorigenesis and malignant transformation. To ensure the fidelity of chromosome transmission, the mitotic spindle is assembled by exquisite mechanisms and orchestrated by centrosomes in animal cells. Centrosomal proteins especially are thought to act coordinately to ensure accurate spindle formation, but the molecular details remain to be investigated. In this study, we report the molecular characterization and functional analysis of a novel centrosomal protein, Cep70. Our data show that Cep70 localizes to the centrosome throughout the cell cycle and binds to the key centrosomal component, gamma-tubulin, through the peptide fragments that contain the coiled-coil domains. Our data further reveal that the centrosomal localization pattern of Cep70 is dependent on its interaction with gamma-tubulin. Strikingly, Cep70 plays a significant role in the organization of both preexisting and nascent microtubules in interphase cells. In addition, Cep70 is necessary for the organization and orientation of the bipolar spindle during mitosis. These results thus report for the first time the identification of Cep70 as an important centrosomal protein that interacts with gamma-tubulin and underscore its critical role in the regulation of mitotic spindle assembly.