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首页> 外文期刊>Cell cycle >APC/C(Cdc20) targets E2F1 for degradation in prometaphase.
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APC/C(Cdc20) targets E2F1 for degradation in prometaphase.

机译：APC / C（CDC20）靶向胰酸糖中降解的E2F1。

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摘要

The mechanisms that control E2F-1 activity are complex. We previously showed that Chk1 and Chk2 are required for E2F1 stabilization and p73 target gene induction following DNA damage. To gain further insight into the processes regulating E2F1 protein stability, we focused our investigation on the mechanisms responsible for regulating E2F1 turnover. Here we show that E2F1 is a substrate of the anaphase promoting complex or cyclosome (APC/C), a ubiquitin ligase that plays an important role in cell cycle progression. Ectopic expression of the APC/C activators Cdh1 and Cdc20 reduced the levels of co-expressed E2F-1 protein. Co-expression of DP1 with E2F1 blocked APC/C-induced E2F1 degradation, suggesting that the E2F1/DP1 heterodimer is protected from APC/C regulation. Following Cdc20 knockdown, E2F1 levels increased and remained stable in extracts over a time course, indicating that APC/C(Cdc20) is a primary regulator of E2F1 stability in vivo. Moreover, cell synchronization experiments showed that siRNA directed against Cdc20 induced an accumulation of E2F1 protein in prometaphase cells. These data suggest that APC/C(Cdc20) specifically targets E2F1 for degradation in early mitosis and reveal a novel mechanism for limiting free E2F1 levels in cells, failure of which may compromise cell survival and/or homeostasis.
机译：控制E2F-1活性的机制是复杂的。我们以前表明，在DNA损伤后，E2F1稳定化和P73靶基因诱导需要CHK1和CHK2。为了进一步了解调节E2F1蛋白稳定性的过程，我们将我们的调查重点调查负责调节E2F1营业额的机制。在这里，我们表明E2F1是促进复合物或环体（APC / C）的后脱脂蛋白酶（APC / C）的底物，其在细胞周期进展中起重要作用。 APC / C活化剂CDH1和CDC20的异位表达降低了共表达的E2F-1蛋白的水平。 DP1与E2F1阻断的APC / C诱导的E2F1降解的共表达，表明E2F1 / DP1异二聚体受到APC / C调节。在CDC20敲低之后，E2F1水平在时间过程中提取物增加并保持稳定，表明APC / C（CDC20）是体内E2F1稳定性的主要调节剂。此外，细胞同步实验表明，针对CDC20的siRNA诱导促果蝇细胞中E2F1蛋白的积累。这些数据表明APC / C（CDC20）特异性靶向E2F1以降解早期丝分裂，并揭示用于限制细胞中的游离E2F1水平的新机制，其可能损害细胞存活和/或稳态。

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