IDENTIFICATION OF PHOSPHORYLATION SITES AURORA B

磷酸化位点 AURORA B 的鉴定

• 批准号: 8171401
• 负责人: Arshad Desai
• 金额: $ 0.24万
• 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/8171401
• 关键词: Anaphase; Cell division; Cells; Centromere; Chromosomes; Complex; Computer Retrieval of Information on Scientific Projects Database; Ensure; Funding; Future; Genome; Grant; In Vitro; Institution; Kinetochores; Mass Spectrum Analysis; Metaphase; Microtubules; Mitotic spindle; Modification; Names; Phosphorylation Site; Phosphotransferases; Post-Translational Protein Processing; Proteins; Regulation; Research; Research Personnel; Resources; Saccharomyces cerevisiae; Saccharomycetales; Signal Transduction; Site; Source; Translations; United States National Institutes of Health; Work; aurora B kinase; base; daughter cell; inner centromere protein; insight; member; segregation

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. During every cell division, the replicated genome must be distributed accurately to daughter cells. Cells use multiple mechanisms to ensure that chromosomes are segregated with high fidelity by the microtubule-based mitotic spindle. One key checkpoint involves the kinase Aurora B, which destabilizes defective kinetochore-microtubule attachments that are not under tension. Aurora B is a member of the chromosomal passenger complex (CPC), a set of interacting proteins named for their localization to the centromere region of chromosomes through metaphase and subsequent relocalization to the central spindle at anaphase. We are studying the regulation of the CPC by post-translation modification in the budding yeast Saccharomyces cerevisiae. We will identify of post-translational modifications by mass spectroscopy of purified CPC phosphorylated by candidate kinases in vitro. Thus far we have identified a number of potential self-regulatory phosphorylation sites on the activator of Aurora B, INCENP. Future work will explore the function of these sites and identify modifications by other regulatory kinases such as Mps1 and Cdk1. This approach will give insight into the local signaling mechanisms that operate during cell division to ensure the coordinated alignment and segregation of all of the chromosomes in a cell.

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。 在每次细胞分裂期间，复制的基因组必须准确地分配给子细胞。 细胞使用多种机制来确保染色体通过基于微管的有丝分裂纺锤体进行高保真度分离。 一个关键的检查点涉及激酶 Aurora B，它会破坏未处于张力下的有缺陷的着丝粒-微管附着物的稳定性。 Aurora B 是染色体乘客复合物 (CPC) 的成员，CPC 是一组相互作用的蛋白质，因其在中期定位于染色体着丝粒区域并随后在后期重新定位于中央纺锤体而得名。 我们正在研究芽殖酵母酿酒酵母中翻译后修饰对 CPC 的调节。 我们将通过候选激酶在体外磷酸化的纯化 CPC 的质谱来鉴定翻译后修饰。 到目前为止，我们已经在 Aurora B 激活剂 INCENP 上鉴定了许多潜在的自我调节磷酸化位点。 未来的工作将探索这些位点的功能并识别其他调节激酶（例如 Mps1 和 Cdk1）的修饰。 这种方法将深入了解细胞分裂过程中运作的局部信号机制，以确保细胞中所有染色体的协调排列和分离。