POST-TRANSLATIONAL MODIFICATION OF SPD-2/5 AND SAS5/6

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 中心体是动物细胞中主要的微管组织中心，发挥着至关重要的作用。 在细胞组织、极性和分裂中的作用。中心体数量、大小异常 在几乎所有人类肿瘤类型中都观察到了形态。 四种蛋白(Spd-2、Spd-5、PLK-1和Aurora-A Kinase)的耗竭。 1))在中心周围物质(PCM)的募集方面存在严重缺陷。 这种招募缺陷导致中心体不能形成适当的 微管的数量，最终经历灾难性的有丝分裂缺陷是正常的 有丝分裂的纺锤体不形成。 我们的目标是试图了解Spd-2、Spd-5、PLK-1和 通过评估AIR-1和PLK-1的激酶活性对中心体的重要性 组装，并使用体外和体内相结合的方法来确定SPD- 2和/或Spd-5是Aurora-A激酶的激活剂或底物。 通过我们与生理蛋白质组学中心(CPP)的合作，我们将使用 SPD-5和SPD-2两种激活酶AIR-1体外检测的质谱学研究 和PLK-1来鉴定被磷酸化修饰的位点。 因此，CPP的贡献对理解中心体组装至关重要 和功能将因此影响我们对癌症、转移和 发展。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Centrosomes, the major microtubule organizing centers in animal cells, perform critical functions in cell organization, polarity and division. Abnormalities in centrosome number, size and morphology have been observed in nearly all human tumor types. Depletion of four proteins (SPD-2, SPD-5, PLK-1 and Aurora-A kinase (AIR- 1)) was shown to have severe defects in the recruitment of pericentriolar material (PCM). This recruitment defect results in centrosomes that are unable to nucleate the proper number of microtubules and ultimately experience catastrophic mitotic defects as proper mitotic spindles do not form. Our goal is try to understand the mechanistic relationship between SPD-2, SPD-5, PLK-1 and AIR-1 by assessing the importance of the kinase activity of AIR-1 and PLK-1 for centrosome assembly, and by using a combination of in vitro and in vivo approaches to determine if SPD- 2 and/or SPD-5 are activators or susbstrates of Aurora-A kinase. Through our collaboration with The Center for Physiological Proteomics (CPP), we will use mass spectrometry after in vitro kinase assays of SPD-5 and SPD-2 with both kinases AIR-1 and PLK-1 to identify the sites that are modified by phosphorylation. The contribution from CPP will therefore be crucial to understanding centrosome assembly and function will therefore impact on our understanding of cancer, metastasis and development.