Interaction between ubiquitin-protein ligase SCFSKP2 and E2F-1 underlies the regulation of E2F-1 degradation
Interaction between ubiquitin-protein ligase SCFSKP2 and E2F-1 underlies the regulation of E2F-1 degradation
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DOI：
10.1038/8984
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发表时间：
1999-05-01
影响因子：
21.3
通讯作者：
Krek, W
中科院分区：
文献类型：
--
作者：
Marti, A;Wirbelauer, C;Krek, W
转录因子E2 F-1在控制细胞增殖中是重要的。它的活性必须以细胞周期依赖性的方式受到严格调控，以使基因表达程序与细胞周期位置密切相关。在这里，我们表明，E2 F-1在细胞周期的G1期晚期积累后，在S/G2期迅速降解。该事件与E2 F-1与含F盒蛋白p45（SKP 2）的特异性相互作用有关，SKP 2是泛素蛋白连接酶SCFSKP 2的细胞周期调节组分，其识别该连接酶的底物。破坏E2 F-1和p45（SKP 2）之间的相互作用导致E2 F-1的泛素化减少以及转录活性E2 F-1蛋白的稳定和积累。这些结果表明，SCFSKP 2依赖的泛素化途径可能参与下调E2 F-1活性在S/G2期的细胞周期，并建议SCFSKP 2和细胞周期依赖的基因控制之间的联系。
The transcription factor E2F-1 is important in the control of cell proliferation. Its activity must be tightly regulated in a cell-cycle-dependent manner to enable programs of gene expression to be coupled closely with cell-cycle position. Here we show that, following its accumulation in the late G1 phase of the cell cycle, E2F-1 is rapidly degraded in S/G2 phase. This event is linked to a specific interaction of E2F-1 with the F-box-containing protein p45(SKP2), which is the cell-cycle-regulated component of the ubiquitin-protein ligase SCFSKP2 that recognizes substrates for this ligase. Disruption of the interaction between E2F-1 and p45(SKP2) results in a reduction in ubiquitination of E2F-1 and the stabilization and accumulation of transcriptionally active E2F-1 protein. These results indicate that an SCFSKP2-dependent ubiquitination pathway may be involved in the downregulation of E2F-1 activity in the S/G2 phase of the cell cycle, and suggest a link between SCFSKP2 and cell-cycle-dependent gene control.