Regulation of Pore Membrane Proteins during NPC Release and Dispersal in Open Mitosis

开放有丝分裂中 NPC 释放和分散过程中孔膜蛋白的调控

• 批准号: 9099322
• 负责人: Joseph Stephen Glavy
• 金额: $ 9.19万
• 依托单位: STEVENS INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-08-15 至 2017-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9099322
• 关键词: Affect; Aging; Alanine; Area; Biological Assay; Cell Cycle; Cell Cycle Progression; Cell division; Cell physiology; Cells; Data; Detection; Dextrans; Disease; Ensure; Eukaryotic Cell; Event; Genomics; Goals; Growth and Development function; Health; Heart Diseases; Individual; Interphase; Kinetochores; Lead; Learning; Life; Location; Malignant Neoplasms; Maps; Measurement; Measures; Membrane; Membrane Proteins; Mitosis; Mitotic; Modeling; Molecular Target; Monitor; Nuclear Envelope; Nuclear Pore Complex; Nuclear Pore Complex Proteins; Pathway interactions; Patients; Peptides; Pharmaceutical Preparations; Phosphorylation; Phosphorylation Site; Phosphotransferases; Plant Roots; Process; Progeria; Protein Region; Proteins; Publishing; RNA Interference; Regulation; Research; Series; Serine; Signal Transduction; Testing; Tyrosine; United States; Validation; Work; base; crosslink; design; expectation; knock-down; leukemia; live cell imaging; mutant; nucleocytoplasmic transport; phosphoproteomics; programs; protein protein interaction; public health relevance; research study; screening

 DESCRIPTION (provided by applicant): The functional integrity of the nuclear pore complex (NPC) is achieved through the fastening to the pore membrane (POM) proteins. This interlocked zipper of proteins is important to maintain nuclear transport and allow proper progression through the cell cycle. NPCs are disassembled into nucleoporins (Nup) subcomplexes during entry into open mitosis in higher eukaryotic cells. POM proteins have been shown to affect cell cycle progression and to be involved in several disease states such as leukemia, heart disease and types of progeria. We hypothesize that Nup/POM interfaces are regulated by mitotic kinases at disassembly leading to their release and mitotic localization. To study this we propose: The determination of key phosphorylation interface targets and pairing them as substrates for kinases involved in disassembly and distribution of the NPC. We will identify and test these regulated areas including constraint-based modeling from our phosphorylation/interaction mapping. This work will be the key prerequisite to understand NPC regulation and distribution throughout the cell cycle.

 描述（由申请方提供）：核孔复合物（NPC）的功能完整性是通过与孔膜（POM）蛋白的结合实现的。蛋白质的这种互锁拉链对于维持核运输并允许通过细胞周期的适当进展是重要的。在高等真核细胞中，NPC在进入开放有丝分裂过程中分解为核孔蛋白（Nup）亚复合物。POM蛋白已被证明影响细胞周期进程，并参与几种疾病状态，如白血病，心脏病和早衰症。我们假设，Nup/POM接口调节有丝分裂激酶在拆卸导致其释放和有丝分裂定位。为了研究这个问题，我们建议：确定关键的磷酸化界面靶点，并将它们配对作为参与NPC分解和分布的激酶的底物。我们将识别和测试这些受监管的领域，包括基于约束的建模从我们的磷酸化/相互作用映射。这项工作将是了解NPC在整个细胞周期中的调控和分布的关键先决条件。