E2F-dependent accumulation of hEmi1 regulates S phase entry by inhibiting APC(Cdh1).
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.
PubMed ID: 11988738
Article link: Nat Cell Biol.
Grant support: CA09302 NCI NIH HHS , GM07365 NIGMS NIH HHS , GM54811 NIGMS NIH HHS , GM60439 NIGMS NIH HHS
Genes referenced: ccnb1.2 cdc20 cdh1 fbxo5 rb1