p78/MCRS1 forms a complex with centrosomal protein Nde1 and is essential for cell viability
p78/MCRS1 forms a complex with centrosomal protein Nde1 and is essential for cell viability
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DOI：
10.1038/sj.onc.1209500
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发表时间：
2006-08-10
期刊：
影响因子：
8
通讯作者：
Greene, M. I.
中科院分区：
文献类型：
--
作者：
Hirohashi, Y.;Wang, Q.;Greene, M. I.
中心体是一种细胞器，作为微管的主要组织中心，在有丝分裂纺锤体的形成和指导染色体的精确分离中起着至关重要的作用。中心体畸变经常与各种形式的人类癌症相关，并且认为该细胞器中的缺陷有助于基因组不稳定性和恶性转化。我们最近发现并表征了一个中心体定位的蛋白质复合物，该复合物由Su 48和Nde 1组成。这些蛋白质的正常功能的破坏导致异常细胞分裂。为了扩展我们对这种蛋白质复合物如何运作的理解，我们试图通过酵母双杂交筛选方法来识别Nde 1相互作用的分子。在这里，我们证明了Nde 1和Su 48都可以与p78/MCRS 1（一种与癌症发展有关的蛋白质）相关联。我们发现，而大多数的p78定位于细胞核中的早期研究报告，一小部分的p78蛋白可以在中心体中检测到。此外，我们确定，一个区域包含叉头相关的结构域的p78参与协会与Nde 1和Su 48，以及在中心体定位。我们还提供了证据表明，p78和Nde 1之间的关联是由Nde 1的磷酸化调节。此外，通过小干扰RNA敲低消除内源性p78功能导致细胞死亡和有丝分裂的适度延迟。这些结果表明，一个子集的p78蛋白组成的中心体和p78是必不可少的细胞活力。
The centrosome, an organelle that functions as the major microtubule-organizing center, plays an essential role in the formation of the mitotic spindle and guiding accurate chromosome segregation. Centrosome aberrations are frequently associated with various forms of human cancers and it is thought that defects in this organelle contribute to genomic instability and malignant transformation. We recently identified and characterized a centrosome-localized protein complex that is comprised of Su48 and Nde1. Disruption of the normal function of these proteins leads to abnormal cell division. To extend our understanding of how this protein complex operates, we sought to identify Nde1-interacting molecules by the yeast two-hybrid screening method. Here, we demonstrate that both Nde1 and Su48 can associate with p78/MCRS1, a protein implicated in cancer development. We found that, whereas the majority of p78 localizes to the nucleus as reported in earlier studies, a fraction of the p78 protein can be detected in the centrosome. Moreover, we determined that a region containing the forkhead-associated domain of p78 is involved in association with Nde1 and Su48, as well as in centrosomal localization. We also provide evidence that the association between p78 and Nde1 is regulated by phosphorylation on Nde1. Furthermore, abrogation of the endogenous p78 function by small interfering RNA knockdown causes cell death and a modest delay in mitosis. These results indicate that a subset of the p78 proteins comprises a component of the centrosome and that p78 is essential for cell viability.