The E2F1-3 transcription factors are essential for cellular proliferation.
In: Nature, Jg. 414 (2001-11-22), Heft 6862, S. 457-62
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Zugriff:
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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The E2F1-3 transcription factors are essential for cellular proliferation.
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Autor/in / Beteiligte Person: | Wu, L ; Timmers, C ; Maiti, B ; Saavedra, HI ; Sang, L ; Chong, GT ; Nuckolls, F ; Giangrande, P ; Wright, FA ; Field, SJ ; Greenberg, ME ; Orkin, S ; Nevins, JR ; Robinson, ML ; Leone, G |
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Zeitschrift: | Nature, Jg. 414 (2001-11-22), Heft 6862, S. 457-62 |
Veröffentlichung: | Basingstoke : Nature Publishing Group ; <i>Original Publication</i>: London, Macmillan Journals ltd., 2001 |
Medientyp: | academicJournal |
ISSN: | 0028-0836 (print) |
DOI: | 10.1038/35106593 |
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