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The E2F1-3 transcription factors are essential for cellular proliferation.

Publication ,  Journal Article
Wu, L; Timmers, C; Maiti, B; Saavedra, HI; Sang, L; Chong, GT; Nuckolls, F; Giangrande, P; Wright, FA; Field, SJ; Greenberg, ME; Orkin, S ...
Published in: Nature
November 2001

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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Published In

Nature

DOI

EISSN

1476-4687

ISSN

0028-0836

Publication Date

November 2001

Volume

414

Issue

6862

Start / End Page

457 / 462

Related Subject Headings

  • Viral Proteins
  • Transcription Factors
  • S Phase
  • Retinoblastoma Protein
  • Mice, Knockout
  • Mice, Inbred C57BL
  • Mice
  • Integrases
  • General Science & Technology
  • Gene Targeting
 

Citation

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Wu, L., Timmers, C., Maiti, B., Saavedra, H. I., Sang, L., Chong, G. T., … Leone, G. (2001). The E2F1-3 transcription factors are essential for cellular proliferation. Nature, 414(6862), 457–462. https://doi.org/10.1038/35106593
Wu, L., C. Timmers, B. Maiti, H. I. Saavedra, L. Sang, G. T. Chong, F. Nuckolls, et al. “The E2F1-3 transcription factors are essential for cellular proliferation.Nature 414, no. 6862 (November 2001): 457–62. https://doi.org/10.1038/35106593.
Wu L, Timmers C, Maiti B, Saavedra HI, Sang L, Chong GT, et al. The E2F1-3 transcription factors are essential for cellular proliferation. Nature. 2001 Nov;414(6862):457–62.
Wu, L., et al. “The E2F1-3 transcription factors are essential for cellular proliferation.Nature, vol. 414, no. 6862, Nov. 2001, pp. 457–62. Epmc, doi:10.1038/35106593.
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. The E2F1-3 transcription factors are essential for cellular proliferation. Nature. 2001 Nov;414(6862):457–462.
Journal cover image

Published In

Nature

DOI

EISSN

1476-4687

ISSN

0028-0836

Publication Date

November 2001

Volume

414

Issue

6862

Start / End Page

457 / 462

Related Subject Headings

  • Viral Proteins
  • Transcription Factors
  • S Phase
  • Retinoblastoma Protein
  • Mice, Knockout
  • Mice, Inbred C57BL
  • Mice
  • Integrases
  • General Science & Technology
  • Gene Targeting