IPL1 REGULATION OF THE ASE1 AND KIP3 PROTEINS

IPL1 对 ASE1 和 KIP3 蛋白的调节

• 批准号: 7420766
• 负责人: Susan Biggins
• 金额: $ 0.29万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-09-20 至 2007-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7420766
• 关键词: chromosome movement; mutant; neoplasm /cancer; proteins; role

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. Ipl1 regulation of the Ase1 and Kip3 proteins Chris Breed, Chitra Kotwaliwale and Sue Biggins Fred Hutchinson Cancer Research Center Chromosomes must accurately segregate to daughter cells to prevent genomic instability and aneuploidy, a hallmark of all tumors. A key regulator of chromosome segregation is Ipl1, the budding yeast homolog of the conserved Aurora protein kinase family. We have found that Ipl1 has roles in kinetochore biorientation, spindle assembly and spindle disassembly. Despite its critical role in multiple processes related to chromosome segregation, the key targets that Ipl1 regulates for these functions are unknown. We have identified two excellent candidate proteins that Ipl1 may regulate to mediate its functions in spindle assembly and spindle disassembly. Because the overexpression of the Ase1 protein suppresses the ipl1 mutant phenotype in spindle assembly, we mutated the five Ipl1 consensus phosphorylation sites in Ase1 (Ase1-5A). Strikingly, the Ase1-5A mutant has the same spindle assembly defects as an ipl1 mutant. Taken together, these data strongly suggest that Ipl1 may phosphorylate Ase1 to regulate spindle assembly. Similarly, we have found a single Ipl1 consensus site mutation in the Kip3 motor protein phenocopies the ipl1 mutant defect in spindle disassembly. In addition, Ipl1 can phosphorylate Ase1 and Kip3 in vitro. Because these studies suggest that Ase1 and Kip3 may be key targets of Ipl1, we propose to determine whether Ase1 and Kip3 are phosphorylated on the Ipl1 consensus sites in vivo.

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得主要资金，因此可以在其他CRISP条目中表示。所列机构为中心，不一定是研究者所在机构。Ipl 1对Ase 1和Kip 3蛋白的调节Chris Breed、Chitra Kotwaliwale和Sue Biggins Fred哈钦森癌症研究中心的染色体必须准确地分离到子细胞，以防止基因组不稳定和非整倍体，这是所有肿瘤的标志。染色体分离的一个关键调节因子是Ipl 1，它是保守的极光蛋白激酶家族的芽殖酵母同系物。我们已经发现Ipl 1在动粒双向定位、纺锤体组装和纺锤体拆卸中起作用。尽管它在与染色体分离相关的多个过程中起着关键作用，但Ipl 1调节这些功能的关键靶点尚不清楚。我们已经确定了两个优秀的候选蛋白，Ipl 1可能调节，以介导其功能的纺锤体组装和纺锤体拆卸。由于Ase 1蛋白的过表达抑制了纺锤体组装中的ipl 1突变表型，我们突变了Ase 1中的5个Ipl 1共有磷酸化位点（Ase 1 -5A）。引人注目的是，Ase 1 -5A突变体具有与ipl 1突变体相同的纺锤体组装缺陷。总之，这些数据强烈表明，Ipl 1可能磷酸化Ase 1调节纺锤体组装。类似地，我们已经发现了一个单一的Ipl 1共识位点突变的Kip 3马达蛋白表型模仿的Ipl 1突变缺陷纺锤体解体。此外，Ipl 1在体外可使Ase 1和Kip 3磷酸化。由于这些研究表明，Ase 1和Kip 3可能是Ipl 1的关键目标，我们建议确定Ase 1和Kip 3是否在体内Ipl 1的一致性位点磷酸化。