The E2F1-3 transcription factors are essential for cellular proliferation - PubMed (original) (raw)
. 2001 Nov 22;414(6862):457-62.
doi: 10.1038/35106593.
C Timmers, B Maiti, H I Saavedra, L Sang, G T Chong, F Nuckolls, P Giangrande, F A Wright, S J Field, M E Greenberg, S Orkin, J R Nevins, M L Robinson, G Leone
Affiliations
- PMID: 11719808
- DOI: 10.1038/35106593
The E2F1-3 transcription factors are essential for cellular proliferation
L Wu et al. Nature. 2001.
Abstract
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.
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