AURORA B PATHWAY PARTIALLY REGULATES SPINDLE ASSEMBLY

AURORA B 通路部分调节主轴组件

• 批准号: 7954103
• 负责人: Hironori Funabiki
• 金额: $ 0.24万
• 依托单位: ROCKEFELLER UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-03-01 至 2010-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7954103
• 关键词: Antibodies; Binding; Bypass; Cells; Chromatin; Complex; Computer Retrieval of Information on Scientific Projects Database; Coupled; Cytoplasm; Funding; Grant; Institution; Manuscripts; Microtubules; Mitotic; Pathway interactions; Phosphoric Monoester Hydrolases; Phosphotransferases; Process; Proteins; Publishing; Regulation; Research; Research Personnel; Resources; Running; Source; Structure; United States National Institutes of Health; Work; Xenopus; aurora B kinase; borealin; egg; macromolecule; survivin

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. Chromatin-induced spindle assembly depends on regulation of microtubule-depolymerizing proteins by the chromosomal passenger complex (CPC), consisting of Incenp, Survivin, Dasra (Borealin), and the kinase Aurora B, but the mechanism and significance of the spatial regulation of Aurora B activity remain unclear. Here, we show that the Aurora B pathway is suppressed in the cytoplasm of Xenopus egg extract by phosphatases, but that it becomes activated by chromatin via a Ran-independent mechanism. While spindle microtubule assembly normally requires Dasra-dependent chromatin binding of the CPC, this function of Dasra can be bypassed by clustering Aurora B-Incenp by using anti-Incenp antibodies, which stimulate autoactivation among bound complexes. However, such chromatin-independent Aurora B pathway activation promotes centrosomal microtubule assembly and produces aberrant achromosomal spindle-like structures. We propose that chromosomal enrichment of the CPC results in local kinase autoactivation, a mechanism that contributes to the spatial regulation of spindle assembly and possibly to other mitotic processes. A manuscript describing this work has been published: Chromosomal enrichment and activation of the aurora B pathway are coupled to spatially regulate spindle assembly. Kelly AE, Sampath SC, Maniar TA, Woo EM, Chait BT, Funabiki H. Dev Cell. 2007 12(1):31-43.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 染色质诱导的纺锤体组装取决于由染色体乘客复合物（CPC）调节微管 - 聚合蛋白的调节，由Incenp，Survivin，Dasra（Borealin）和激酶Aurora B组成，但Aurora B活动的机制和意义仍然不存在。在这里，我们表明Aurora B途径在磷酸酶的Xenopus鸡蛋提取物的细胞质中抑制，但它通过染色质通过RAN独立的机制而被染色质激活。虽然纺锤微管组件通常需要CPC的DASRA依赖性染色质结合，但DASRA的这种功能可以通过使用抗Incenp抗体来绕过Aurora b-Incenp来绕过，从而刺激结合复合物之间的自动激活。然而，这种非染色质的Aurora B途径激活促进了中心体微管组装，并产生异常的Achromosomal纺锤体样结构。我们提出，CPC的染色体富集会导致局部激酶自动激活，该机制有助于纺锤体组装的空间调节以及可能有可能促进其他有丝分裂过程。描述这项工作的手稿已经发表： Aurora B途径的染色体富集和激活与空间调节主轴组件耦合。 Kelly AE，Sampath SC，Maniar TA，Woo EM，Chait BT，Funabiki H. Dev Cell。 2007 12（1）：31-43。