Chromosome Movement in Prometaphase

前中期染色体运动

• 批准号: 7999990
• 负责人: GARY J. GORBSKY
• 金额: $ 9.17万
• 依托单位: OKLAHOMA MEDICAL RESEARCH FOUNDATION
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-01-07 至 2010-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7999990
• 关键词: Algorithms; Anaphase; Antibodies; Antineoplastic Agents; Area; Binding Proteins; Cell Cycle; Cell Cycle Regulation; Cell Extracts; Cell Nucleus; Cell division; Cells; Chromosome Segregation; Chromosomes; Code; Complex; Congenital Abnormality; Cyclins; Cytoplasm; Cytoplasmic Organelle; Data; Disease; Ensure; Enzymes; Equilibrium; Event; Funding; Genes; Goals; Human Genome; Intervention; Investigation; Kinetochores; Life; Malignant Neoplasms; Mass Spectrum Analysis; Mediating; Meta-Analysis; Metaphase; Microtubules; Mitosis; Mitotic; Mitotic spindle; Mitotic/Spindle Checkpoint; Movement; Mutate; Names; Normal Cell; Normal Statistical Distribution; Nuclear; Nuclear Envelope; Open Reading Frames; Paclitaxel; Pathway interactions; Phenotype; Phosphoric Monoester Hydrolases; Phosphorylation; Phosphorylation Site; Phosphotransferases; Play; Post-Translational Protein Processing; Process; Prometaphase; Prophase; Proteins; Publishing; Regulation; Research; Research Personnel; Role; Signal Pathway; Signal Transduction; Small Interfering RNA; Testing; Therapeutic; Time; Troglodytinae; Ubiquitin; aurora-A kinase; cancer cell; cancer therapy; chromosome movement; enzyme activity; human disease; improved; interest; molecular mechanics; novel; overexpression; public health relevance; response; segregation; text searching

DESCRIPTION (provided by applicant): The long term objectives of this project are to understand the mechanisms that regulate chromosome movement and cell cycle control in mitosis. Balanced chromosome segregation in mitosis occurs through complex spatial and temporal regulation of enzyme activities, particularly kinases, phosphatases and enzymes of the ubiquitin cascade. Mitosis also involves highly dynamic and structural reorganization of nuclear and cytoplasmic organelles. Of particular interest in this project are the molecular mechanics of chromosome attachment to and movement on the microtubules of the mitotic spindle. The other main focus is cell cycle control of enzyme activities and their consequences for regulating mitotic progression and the mitotic spindle checkpoint. The mitotic spindle checkpoint is essential in ensuring the normal distribution of chromosomes. It is often defective in cancer cells and it plays a key role in the response of cells to therapeutic anti-cancer drugs such as paclitaxel. The current proposal consists of three aims. Two of the aims are focused on characterization of an entirely novel protein called Kinetochore Protein 1 (Kinp1). Preliminary data indicate that Kinp1 plays an essential role in normal microtubule-kinetochore attachment and/or in regulation of the mitotic spindle checkpoint. The other aim is focused on the general role of nuclear envelope integrity in controlling early events in mitosis. Accomplishing the goals proposed will add significantly to our understanding of cell cycle control of cell division in normal cells and contribute toward understanding how these controls become aberrant in chromosomal imbalances that contribute to human disease such as birth defects and cancer. PUBLIC HEALTH RELEVANCE: This project seeks to define novel aspects of the regulation of cell division in normal and cancer cells. Many of the control mechanisms in cancer cells are abnormal in cancer and these differences provide opportunities to target cancer cells specifically with new therapies. This project will also help us to understand how many current cancer therapies target cells and thus how these therapies can be improved. The results from this study will also enlighten the mechanisms that contribute to chromosome imbalances that are the cause of many birth defects.

描述（由申请人提供）：该项目的长期目标是了解调节有丝分裂中染色体运动和细胞周期控制的机制。有丝分裂中平衡的染色体分离是通过酶活性的酶活性的复杂空间和时间调节而发生的，尤其是泛素级联酶的激酶，磷酸酶和酶。有丝分裂还涉及核和细胞质细胞器的高度动态和结构重组。在该项目中特别感兴趣的是染色体附着的分子力学和有丝分裂纺锤体的微管上的运动。另一个主要重点是酶活性的细胞周期控制及其对调节有丝分裂进展和有丝分裂主轴检查点的后果。有丝分裂主轴检查点对于确保染色体的正态分布至关重要。它通常在癌细胞中有缺陷，并且在细胞对治疗性抗癌药物（如紫杉醇）的反应中起关键作用。当前的提议包括三个目标。其中两个目的集中在表征一种称为Kinetochore蛋白1（KINP1）的完全新颖的蛋白质。初步数据表明，KINP1在正常的微管 - 金属码附件和/或有丝分裂纺锤体检查点的调节中起着至关重要的作用。另一个目的集中在核包膜完整性在控制有丝分裂早期事件中的一般作用。实现提出的目标将大大增加我们对正常细胞细胞分裂细胞周期控制的理解，并有助于了解这些对照在染色体失衡中如何变得异常，从而导致人类疾病，例如先天缺陷和癌症。公共卫生相关性：该项目旨在定义正常和癌细胞中细胞分裂调节的新方面。癌细胞中的许多控制机制在癌症中都是异常的，这些差异为专门针对新疗法的癌细胞提供了机会。该项目还将帮助我们了解当前有多少癌症靶向细胞，从而如何改善这些疗法。这项研究的结果还将启发导致染色体失衡的机制，这些机制是许多先天缺陷的原因。