MECHANISMS OF CELL PROLIFERATION FOLLOWING PERTURBATIONS

扰动后细胞增殖的机制

• 批准号: 6320825
• 负责人: Prabhat C Goswami
• 金额: $ 15.32万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-07-01 至 2001-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6320825
• 关键词: HeLa cells; cell cycle; cell proliferation; gene expression; human tissue; messenger RNA; molecular biology; pathologic process; phenotype; retinoblastoma protein; tissue /cell culture; transcription factor

The objective of the proposed research is to determine the mechanisms of acceleration in G 1- transit following a reversible block of cell cycle progression in S-phase of the preceding generation. A possible mechanism for this phenomenon is that delayed progression in S-phase can trigger biochemical processes pertinent to the subsequent G 1-phase prior to the completion of mitosis. In Specific Aim 1, we will determine if cell cycle perturbations that lead to G 1- acceleration in HeLa cells have similar effects in other human cell lines of both normal and transformed phenotypes. Detailed kinetic analyses will be used to completely map the competence window, i.e., the cell cycle time between early S and M phases in which delayed progression results in G 1- acceleration. In Specific Aim 2, will determine if accelerated G 1 transit is due to an alteration in the expression of known G 1- regulatory proteins. The work proposed in Specific Aim 3 will determine whether accelerated G 1-transit following S-phase perturbation results in an unscheduled inactivation of the Retinoblastoma protein and determine, whether such a mechanism can abrogate the ionizing radiation-induced G 1-arrest. In Specific Aim 4 we will determine which specific mRNA species contribute to the altered expression of G 1-regulatory proteins observed in Aim 2 which are associated with G 1-acceleration. The results obtained from completion of this study will characterize the mechanisms involved in recover from cell-cycle perturbation, and verify the idea that early G1 events can be influenced by biochemical processes occurring prior to the completion of mitosis.

拟议研究的目的是确定 可逆后 G 1- 过境的加速机制 前面的 S 期细胞周期进展受阻 一代。 这种现象的一个可能的机制是 S 期进展延迟可触发生化过程 与完成之前的后续 G 1 阶段相关 有丝分裂。 在具体目标 1 中，我们将确定细胞周期是否 导致 HeLa 细胞中 G 1- 加速的扰动具有类似的 对正常和转化的其他人类细胞系的影响 表型。 详细的动力学分析将用于完全 绘制能力窗口，即早期之间的细胞周期时间 S 期和 M 期，延迟进展导致 G 1- 加速度。 在特定目标 2 中，将确定是否加速 G 1 转运是由于已知 G 1- 表达的改变所致 调节蛋白。 具体目标 3 中提出的工作将 确定 S 相之后是否加速 G 1 过渡 扰动会导致非计划性失活 视网膜母细胞瘤蛋白并确定，是否有这样的机制 可以消除电离辐射引起的G 1 逮捕。 具体来说 目标 4 我们将确定哪些特定 mRNA 物种有助于 在目标 2 中观察到 G 1 调节蛋白表达的改变 与 G 1 加速度相关。 得到的结果 这项研究完成后将描述其机制 参与从细胞周期扰动中恢复，并验证这个想法 早期 G1 事件可能受到生化过程的影响 发生在有丝分裂完成之前。