The E2F1–3 transcription factors are essential for cellular proliferation

被引:0
作者
Lizhao Wu
Cynthia Timmers
Baidehi Maiti
Harold I. Saavedra
Ling Sang
Gabriel T. Chong
Faison Nuckolls
Paloma Giangrande
Fred A. Wright
Seth J. Field
Michael E. Greenberg
Stuart Orkin
Joseph R. Nevins
Michael L. Robinson
Gustavo Leone
机构
[1] Immunology and Medical Genetics,Division of Human Cancer Genetics, Department of Molecular Virology, and Department of Molecular Genetics
[2] The Ohio State University,Division of Molecular and Human Genetics
[3] Children's Research Institute,Department of Genetics
[4] The Ohio State University,Department of Neuroscience
[5] Howard Hughes Medical Institute,undefined
[6] Duke University Medical Center,undefined
[7] Harvard Medical School,undefined
[8] Howard Hughes Medical Institute,undefined
[9] Children's Hospital,undefined
[10] Harvard Medical School,undefined
来源
Nature | 2001年 / 414卷
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摘要
The retinoblastoma tumour suppressor (Rb) pathway is believed to have a critical role in the control of cellular proliferation by regulating E2F activities1,2. E2F1, E2F2 and E2F3 belong to a subclass of E2F factors thought to act as transcriptional activators important for progression through the G1/S transition3. 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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页码:457 / 462
页数:5
相关论文
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