The role of the NIMA kinase in mitotic regulation

NIMA 激酶在有丝分裂调节中的作用

• 批准号: 7490574
• 负责人: STEPHEN A OSMANI
• 金额: $ 31.89万
• 依托单位: OHIO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1989
• 资助国家: 美国
• 起止时间: 1989-07-01 至 2010-01-03
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7490574
• 关键词: Address; Affect; Alleles; Aneuploidy; Architecture; Arts; Aspergillus nidulans; Back; Cell Cycle; Chromatin; Chromosomes; Complex; Defect; Diffusion; Dominant-Negative Mutation; Ectopic Expression; Electron Microscopy; Genetic Models; Human; Interphase; Interphase Cell; Laboratories; Lead; Life; Location; Malignant Neoplasms; Mammalian Cell; Maps; Medical; Mitosis; Mitotic; Mitotic Chromosome; Modeling; Molds; NIMA; Nuclear Pore Complex; Nuclear Pore Complex Proteins; Phosphorylation; Phosphorylation Site; Phosphotransferases; Play; Protein Kinase; Regulation; Role; Structure; System; Temperature; Testing; Yeasts; base; deletion analysis; innovation; novel; research study

DESCRIPTION (provided by applicant): Mitotic regulation is fundamentally important to all eukaryotic life and has medical significance as mitotic defects can lead to aneuploidy and cancer. Mitosis is regulated by a complex interplay of conserved protein kinases but there is a limited understanding of the pertinent kinase substrates and the mechanistic consequences of their phosphorylation. For example, it is unknown how mitotic kinases regulate the stepwise disassembly and reassembly of the nuclear pore complex (NPC) during open mitosis. My laboratory has shown that during the closed mitosis of the model filamentous fungus Aspergillus nidulans, the NPC is partially disassembled with at least 12 NPC proteins (Nups) reversibly dispersing from a core NPC structure. A. nidulans therefore represents a unique and powerful model genetic system in which the NPC is regulated during mitosis in a manner displaying many similarities to human mitotic NPC regulation. Interestingly, A. nidulans An-Nup2 exclusively re-locates to mitotic chromosomes, suggesting a novel mitotic role for this Nup. This proposal aims to: i) Define in detail the reversible changes in the composition of the NPC during mitosis, ii) Characterize how NPC architecture changes when it is disassembled and assembled and relate this to NPC composition and function, iii) Establish how mitotic specific phosphorylation regulates the structure and function of the NPC, and iv) Determine how the localization of An-Nup2 to chromatin helps coordinate NPC disassembly/reassembly with mitotic progression. These studies will help define how the NPC is regulated by kinases during mitosis and how the mitotic regulation of Nups is integrated with mitotic progression.

描述（由申请人提供）：有丝分裂调节对所有真核生活至关重要，并且具有医学意义，因为有丝分裂缺陷会导致非整倍性和癌症。有丝分裂受到保守蛋白激酶的复杂相互作用的调节，但对相关激酶底物的理解和磷酸化的机械后果有限。例如，尚不清楚有丝分裂激酶如何调节开放有丝分裂过程中核孔复合物（NPC）的逐步拆卸和重新组装。我的实验室表明，在模型丝状真菌的闭合有丝分裂期间，NPC部分与至少12个NPC蛋白（NUPS）部分分解，可从核心NPC结构可逆地分散。因此，Nidulans代表了一个独特而强大的模型遗传系统，其中在有丝分裂过程中调节NPC的方式与人类有丝分裂NPC调节的方式表现出许多相似之处。有趣的是，Nidulans an-Nup2独家重新定位到有丝分裂染色体，这表明该NUP具有新颖的有丝分裂作用。该建议的目的是：i）详细定义有丝分裂过程中NPC组成的可逆变化，ii）在NPC体系结构被拆卸和组装时如何变化，并将其与NPC组成和功能相关联，与NPC组成和功能相关联，III） NPC拆卸/重新组装有丝分裂进展。这些研究将有助于定义NPC在有丝分裂过程中如何受激酶的调节，以及如何将NUP的有丝分裂调节与有丝分裂进展整合在一起。