THE RB-E2F INTERACTION & ITS REGULATION BY PHOSPHORYLATION

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 哺乳动物细胞周期的G1和S阶段之间的过渡需要参与生长和DNA合成的许多基因的转录激活。 这一过程主要由E2 F蛋白进行，在G 0和G1早期由Rb严格调控，Rb抑制E2 F活性并招募其他阻遏物到E2 F启动子。细胞周期蛋白依赖性激酶对Rb的磷酸化导致其失活，随后通过E2 F激活进行细胞周期分裂。 因此，在许多人类癌症中存在使Rb组成型失活的基因改变，无论是Rb本身还是调节Rb的蛋白质。 Rb通过在A/B口袋处结合E2 F反式激活结构域部分地抑制E2 F基因的转录;然而，C末端结构域（RbC）对于生长抑制和E2 F转录和结合测定中的完全Rb活性也是必需的。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The transition between the G1 and S stages of the mammalian cell cycle requires the transcriptional activation of a number of genes involved in growth and DNA synthesis. This process, primarily carried out by E2F proteins, is tightly regulated in G0 and early G1 by Rb, which inhibits E2F activity and recruits other repressors to E2F promoters. Phosphorylation of Rb by cyclin-dependent kinases leads to its inactivation and subsequent progression through the cell cycle towards division via E2F activation. Accordingly, genetic alterations, either in Rb itself or in the proteins that regulate it, that render Rb constitutively inactive are present in a number of human cancers. Rb inhibits the transcription of E2F genes in part by binding the E2F transactivation domain at the A/B pocket; however, the C-terminal domain (RbC) is also necessary for full Rb activity in growth suppression and E2F transcription and binding assays.