E2F-dependent accumulation of hEmi1 regulates S phase entry by inhibiting APCCdh1
E2F-dependent accumulation of hEmi1 regulates S phase entry by inhibiting APCCdh1
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DOI：
10.1038/ncb785
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发表时间：
2002-05-01
影响因子：
21.3
通讯作者：
Jackson, PK
中科院分区：
文献类型：
--
作者：
Hsu, JY;Reimann, JDR;Jackson, PK
在非洲爪蟾胚胎中，Cdc 1通过抑制APC（Cdc 20）泛素化复合物以允许细胞周期蛋白B积累来促进有丝分裂进入。我们在这里表明，人类HLA-B1（hLA-B1）的功能，以促进细胞周期蛋白A的积累和S期进入体细胞抑制APC（Cdh 1）复合物。在G1-S转换时，hB 1由E2 F转录因子转录诱导，很像细胞周期蛋白A。hdh 1过表达加速S期进入，并且可以覆盖由Cdh 1或E2 F抑制剂p105视网膜母细胞瘤蛋白（pRb）过表达引起的G1阻滞。通过RNA干扰耗尽细胞中的hB 1阻止细胞周期蛋白A的积累并抑制S期进入。这些数据表明，E2 F可以激活细胞周期蛋白A的转录和APC（Cdh 1）靶点，如细胞周期蛋白A，以促进S期进入的haplo 1依赖性稳定。
Emi1 promotes mitotic entry in Xenopus laevis embryos by inhibiting the APC(Cdc20) ubiquitination complex to allow accumulation of cyclin B. We show here that human Emi1 (hEmi1) functions to promote cyclin A accumulation and S phase entry in somatic cells by inhibiting the APC(Cdh1) complex. At the G1-S transition, hEmi1 is transcriptionally induced by the E2F transcription factor, much like cyclin A. hEmi1 overexpression accelerates S phase entry and can override a G1 block caused by overexpression of Cdh1 or the E2F-inhibitor p105 retinoblastoma protein (pRb). Depleting cells of hEmi1 through RNA interference prevents accumulation of cyclin A and inhibits S phase entry. These data suggest that E2F can activate both transcription of cyclin A and the hEmi1-dependent stabilization of APC(Cdh1) targets, such as cyclin A, to promote S phase entry.