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。子项目和 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。 染色质诱导的纺锤体组装依赖于染色体过客复合物（CPC）对微管解聚蛋白的调节，CPC由Incenp、Survivin、Dasra（Borealin）和激酶Aurora B组成，但Aurora空间调节的机制和意义B活动仍不清楚。在这里，我们发现非洲爪蟾卵提取物细胞质中的 Aurora B 途径被磷酸酶抑制，但它通过一种不依赖于 Ran 的机制被染色质激活。虽然纺锤体微管组装通常需要 CPC 的 Dasra 依赖性染色质结合，但可以通过使用抗 Incenp 抗体聚集 Aurora B-Incenp 来绕过 Dasra 的这一功能，该抗体刺激结合复合物之间的自动激活。然而，这种不依赖于染色质的 Aurora B 通路激活会促进中心体微管组装并产生异常的非染色体纺锤体样结构。我们提出，CPC 的染色体富集会导致局部激酶自动激活，这种机制有助于纺锤体组装的空间调节，并可能有助于其他有丝分裂过程。描述这项工作的手稿已经出版： 染色体富集和 Aurora B 通路激活相结合，在空间上调节纺锤体组装。 Kelly AE、Sampath SC、Maniar TA、Woo EM、Chait BT、Funabiki H. Dev Cell。 2007 12(1):31-43。