Core A: Determining and targeting mechanisms controlling cancer cell division

项目总结 癌基因的功能获得突变和抑癌基因的功能丧失突变推动了 人类癌症的发生和发展。这些基因也在正常发育和 细胞分化。Rb途径中的遗传或表观遗传改变是启动和 大多数类型的人类癌症的进展。该计划中的三个相互关联的项目将涉及主要 关于Rb通路中关键蛋白功能的悬而未决的基本问题：细胞周期蛋白D-CDK4/6 通过磷酸化调节Rb的癌蛋白，Rb家族的肿瘤抑制因子作为转录因子 以及与RB家族相互作用并直接受RB家族调控的E2F转录因子家族 蛋白质和控制对细胞周期进程重要的基因的转录。这项计划的一个主要目标 项目是使用跨学科的方法来研究RB途径。这个核心的主要目标是 提供一个行政框架，以帮助实现科学目标和传播 拟议的实验。 具体地说，行政核心将有三个目标。第一个目标将是促进科学互动 在参与三个主要项目和两个科学核心的项目负责人和实验室成员中。 第二个目标将是提供科学和财务指导和监督，包括与 一个内部咨询委员会和一个外部科学咨询委员会。第三个目标将是促进 项目成员和核心成员之间的沟通，以及与更大的科学界的沟通 社区和公众。为实现这些目标，该行政核心领导将与 每个项目和科学核心的负责人。定期进行科学互动，以交流思想和 结果、内部咨询委员会和外部科学咨询委员会成员的反馈， 以及监控进展的具体指标，都将是帮助发现新的基本机制的关键 潜在的细胞周期进程。

PROJECT SUMMARY Gain-of-function mutations of oncogenes and loss-of-function mutations of tumor suppressor genes drive the initiation and progression of human cancer. These genes also play critical roles in normal development and cellular differentiation. Genetic or epigenetic alterations in the Rb pathway are required for the initiation and progression of most types of human cancer. The three inter-related projects in this program will address major outstanding fundamental questions about the functioning of key proteins in the Rb pathway: Cyclin D-Cdk4/6 oncoproteins that regulate Rb by phosphorylation, the Rb family of tumor suppressors that act as transcriptional regulators, and the E2F family of transcription factors that interact with and are directly regulated by the Rb family proteins and control the transcription of genes important for cell cycle progression. A major goal of this program project is to investigate the Rb pathway using an interdisciplinary approach. The major goal of this Core is to provide an administrative framework to help implement the scientific goals and disseminate the results of the proposed experiments. Specifically, the Administrative Core will have three goals. The first goal will be to promote scientific interactions among the Project Leaders and laboratory members involved in the three main Projects and two Scientific Cores. The second goal will be to provide scientific and financial guidance and oversight, including in conjunction with an Internal Advisory Committee and an External Scientific Advisory Board. The third goal will be to facilitate communication among the members of the Projects and Cores themselves and to the greater scientific community and the public. To achieve these goals, the Leader for this Administrative Core, will work closely with the Leaders of each of the Projects and Scientific Cores. Regular scientific interactions to exchange ideas and results, feedback from members of the internal advisory committee and the external scientific advisory board, and specific metrics to monitor progress, will all be critical to help uncover novel fundamental mechanisms underlying cell cycle progression.