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

SPD-2/5 和 SAS5/6 的翻译后修饰

• 批准号: 8171369
• 负责人: Karen F Oegema
• 金额: $ 0.47万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-09-01 至 2011-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8171369
• 关键词: Animals; Biological Assay; Cells; Centrosome; Collaborations; Computer Retrieval of Information on Scientific Projects Database; Defect; Development; Funding; Goals; Grant; Human; In Vitro; Institution; Mass Spectrum Analysis; Microtubule-Organizing Center; Microtubules; Mitotic; Mitotic spindle; Morphology; Neoplasm Metastasis; Phosphorylation; Phosphotransferases; Physiological; Post-Translational Protein Processing; Proteins; Proteomics; Research; Research Personnel; Resources; Site; Source; United States National Institutes of Health; aurora-A kinase; experience; in vivo; tumor

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.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目及 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 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、极性和分裂中发挥作用。中心体数量、大小异常 几乎在所有人类肿瘤类型中都观察到了其形态和形态。 四种蛋白质（SPD-2、SPD-5​​、PLK-1 和 Aurora-A 激酶 (AIR- 1））被证明在中心粒周围材料（PCM）的募集方面存在严重缺陷。 这种募集缺陷导致中心体无法正确成核 微管数量并最终经历灾难性的有丝分裂缺陷 有丝分裂纺锤体不形成。 我们的目标是尝试了解 SPD-2、SPD-5​​、PLK-1 和 AIR-1 通过评估 AIR-1 和 PLK-1 激酶活性对中心体的重要性 组装，并通过使用体外和体内方法的组合来确定 SPD- 2和/或SPD-5​​是Aurora-A激酶的激活剂或底物。 通过与生理蛋白质组学中心 (CPP) 的合作，我们将使用 使用两种激酶 AIR-1 对 SPD-5​​ 和 SPD-2 进行体外激酶测定后的质谱分析 和 PLK-1 来识别被磷酸化修饰的位点。 因此，CPP 的贡献对于理解中心体组装至关重要 因此，功能将影响我们对癌症、转移和 发展。