| First Author | Wu L | Year | 2001 |
| Journal | Nature | Volume | 414 |
| Issue | 6862 | Pages | 457-62 |
| PubMed ID | 11719808 | Mgi Jnum | J:73374 |
| Mgi Id | MGI:2155020 | Doi | 10.1038/35106593 |
| Citation | Wu L, et al. (2001) The E2F1-3 transcription factors are essential for cellular proliferation. Nature 414(6862):457-62 |
| abstractText | The retinoblastoma tumour suppressor (Rb) pathway is believed to have a critical role in the control of cellular proliferation by regulating E2F activities. E2F1, E2F2 and E2F3 belong to a subclass of E2F factors thought to act as transcriptional activators important for progression through the G1/S transition. Here we show, by taking a conditional gene targeting approach, that the combined loss of these three E2F factors severely affects E2F target expression and completely abolishes the ability of mouse embryonic fibroblasts to enter S phase, progress through mitosis and proliferate. Loss of E2F function results in an elevation of p21Cip1 protein, leading to a decrease in cyclin-dependent kinase activity and Rb phosphorylation. These findings suggest a function for this subclass of E2F transcriptional activators in a positive feedback loop, through down-modulation of p21Cip1, that leads to the inactivation of Rb-dependent repression and S phase entry. By targeting the entire subclass of E2F transcriptional activators we provide direct genetic evidence for their essential role in cell cycle progression, proliferation and development. |
