Emi1 (for early mitotic inhibitor) regulates mitosis by inhibiting the anaphase promoting complex/cyclosome (APC). Emi1 is a conserved F box protein containing a zinc binding region essential for APC inhibition. The Emi1 protein functions to promote cyclin A accumulation and S phase entry in somatic cells by inhibiting the APC complex. At the G1-S transition, Emi1 is transcriptionally induced by the E2F transcription factor. Emi1 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 Emi1 through RNA interference prevents accumulation of cyclin A and inhibits S phase entry. Emi1 is required to arrest unfertilized eggs at metaphase of meiosis II and may be the long-sought mediator of CSF activity. Human Emi1 is similar to Xenopus laevis Emi1, which inhibits the APC (Cdc20) ubiquitination complex to allow accumulation of cyclin B.