G1 期 Cyclin D 相关事件
中文名称
通路描述
三种 D 型 Cyclin 对于从 G1 到 S 相位的进展是必需的。这些 D 型 Cyclin 结合并激活 CDK4 和 CDK6。D 型 Cyclin 与 CDK4/6 的所有可能复合物的形成由 p21(CIP1/WAF1) 和 p27(KIP1) 等蛋白促进。随后,CDK 依赖性的激酶因 CAK 的磷酸化而激活。CDK 依赖性的激酶磷酸化 RB1 蛋白和 RB1 相关蛋白 p107(RBL1)和 p130(RBL2)。RB1 的磷酸化导致激活的 E2F 转录因子(E2F1、E2F2 和 E2F3)的释放。当抑制性 E2F(E2F4 和 E2F5)从磷酸化的 RBL1 和 RBL2 解离后,激活的 E2F 结合到 E2F 启动子位点,刺激细胞周期基因的转录,从而结果导致适当的 G1/S 过渡。p27Kip 的结合和隔离也可能有助于 G1/S 过渡时 CDK2 Cyclin E/CDK2 Cyclin A 复合物的激活(Yew 等,2001)。
英文描述
Cyclin D associated events in G1 Three D-type cyclins are essential for progression from G1 to S-phase. These D cyclins bind to and activate both CDK4 and CDK6. The formation of all possible complexes between the D-type cyclins and CDK4/6 is promoted by the proteins, p21(CIP1/WAF1) and p27(KIP1). The cyclin-dependent kinases are then activated due to phosphorylation by CAK. The cyclin dependent kinases phosphorylate the RB1 protein and RB1-related proteins p107 (RBL1) and p130 (RBL2). Phosphorylation of RB1 leads to release of activating E2F transcription factors (E2F1, E2F2 and E2F3). After repressor E2Fs (E2F4 and E2F5) dissociate from phosphorylated RBL1 and RBL2, activating E2Fs bind to E2F promoter sites, stimulating transcription of cell cycle genes, which then results in proper G1/S transition. The binding and sequestration of p27Kip may also contribute to the activation of CDK2 cyclin E/CDK2 cyclin A complexes at the G1/S transition (Yew et al., 2001).
所含基因
46 个基因