E2F-dependent accumulation of hEmi1 regulates S phase entry by inhibiting APCCdh1

被引：275

作者：

Hsu, JY

Reimann, JDR

Sorensen, CS

Lukas, J

Jackson, PK ^{[1
]}

机构：

[1] Stanford Univ, Sch Med, Dept Pathol, Stanford, CA 94305 USA

[2] Stanford Univ, Sch Med, Dept Microbiol & Immunol, Stanford, CA 94305 USA

[3] Stanford Univ, Sch Med, Program Biophys, Stanford, CA 94305 USA

[4] Stanford Univ, Sch Med, Program Canc Biol, Stanford, CA 94305 USA

[5] Danish Canc Soc, Inst Canc Biol, DK-2100 Copenhagen, Denmark

来源：

NATURE CELL BIOLOGY | 2002年 / 4卷 / 05期

关键词：

D O I：

10.1038/ncb785

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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.

引用

页码：358 / 366

页数：9

共 48 条

[31] Inhibition of Cdh1-APC by the MAD2-related protein MAD2L2: a novel mechanism for regulating Cdh1 [J].