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The E2F1–3 transcription factors are essential for cellular proliferation

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Listed:
  • Lizhao Wu

    (Immunology and Medical Genetics, The Ohio State University)

  • Cynthia Timmers

    (Immunology and Medical Genetics, The Ohio State University)

  • Baidehi Maiti

    (Immunology and Medical Genetics, The Ohio State University)

  • Harold I. Saavedra

    (Immunology and Medical Genetics, The Ohio State University)

  • Ling Sang

    (Immunology and Medical Genetics, The Ohio State University)

  • Gabriel T. Chong

    (Immunology and Medical Genetics, The Ohio State University)

  • Faison Nuckolls

    (Howard Hughes Medical Institute, Duke University Medical Center)

  • Paloma Giangrande

    (Howard Hughes Medical Institute, Duke University Medical Center)

  • Fred A. Wright

    (Immunology and Medical Genetics, The Ohio State University)

  • Seth J. Field

    (Harvard Medical School)

  • Michael E. Greenberg

    (Harvard Medical School)

  • Stuart Orkin

    (Howard Hughes Medical Institute, Children's Hospital, Harvard Medical School)

  • Joseph R. Nevins

    (Howard Hughes Medical Institute, Duke University Medical Center)

  • Michael L. Robinson

    (Children's Research Institute, The Ohio State University)

  • Gustavo Leone

    (Immunology and Medical Genetics, The Ohio State University)

Abstract

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.

Suggested Citation

  • 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 O, 2001. "The E2F1–3 transcription factors are essential for cellular proliferation," Nature, Nature, vol. 414(6862), pages 457-462, November.
    • Handle: RePEc:nat:nature:v:414:y:2001:i:6862:d:10.1038_35106593
    DOI: 10.1038/35106593
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