Characterization of Su48, a centrosome protein essential for cell division.
Characterization of Su48, a centrosome protein essential for cell division.
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DOI：
10.1073/pnas.0601682103
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发表时间：
2006-04
影响因子：
11.1
通讯作者：
Qiang Wang;Xiulian Du;J. Meinkoth;Y. Hirohashi;Hongtao Zhang;Q. Liu;M. Richter;M. Greene
中科院分区：
文献类型：
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作者：
Qiang Wang;Xiulian Du;J. Meinkoth;Y. Hirohashi;Hongtao Zhang;Q. Liu;M. Richter;M. Greene
中心体作为主要的微管组织中心，在有丝分裂过程中引导染色体分离中发挥着至关重要的作用。中心体异常常见于多种癌症，表明该细胞器的功能障碍可能导致恶性转化。在我们努力鉴定中心体的蛋白质成分并了解该细胞器的组装和功能所涉及的结构特征的过程中，我们克隆并表征了一种称为 Su48 的中心体相关蛋白质。我们发现 Su48 的包含卷曲线圈的子结构域对于其中心体定位来说既是足够的也是必需的。此外，该结构还调节Su48二聚化。此外，Su48 的异位表达会导致异常有丝分裂，而 Su48 的突变形式会破坏 γ-微管蛋白在中心体的定位。最后，通过显微注射抗 Su48 抗体，我们发现正常 Su48 功能的破坏会导致有丝分裂失败，这可能是由于中心体缺陷或不完全胞质分裂所致。因此，Su48 代表了一种以前未被识别的中心体蛋白，它对于细胞分裂至关重要。我们推测 Su48 异常可能导致染色体分离异常，并可能导致非整倍体和恶性转化。
The centrosome functions as the major microtubule-organizing center and plays a vital role in guiding chromosome segregation during mitosis. Centrosome abnormalities are frequently seen in a variety of cancers, suggesting that dysfunction of this organelle may contribute to malignant transformation. In our efforts to identify the protein components of the centrosome and to understand the structure features involved in the assembly and functions of this organelle, we cloned and characterized a centrosome-associated protein called Su48. We found that a coiled coil-containing subdomain of Su48 was both sufficient and required for its centrosome localization. In addition, this structure also modulates Su48 dimerization. Moreover, ectopic expression of Su48 causes abnormal mitosis, and a mutant form of Su48 disrupts the localization of gamma-tubulin to the centrosome. Finally, by microinjection of an anti-Su48 antibody, we found that disruption of normal Su48 functions leads to mitotic failure, possibly due to centrosome defects or incomplete cytokinesis. Thus, Su48 represents a previously unrecognized centrosome protein that is essential for cell division. We speculate that Su48 abnormalities may cause aberrant chromosome segregation and may contribute to aneuploidy and malignant transformation.