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Constitutive expression of E2F-1 leads to p21-dependent cell cycle arrest in S phase of the cell cycle

Oncogene volume 23, pages 4173–4176 (2004)Cite this article

Abstract

p21 is a potent inhibitor of cyclin-dependent kinases capable of arresting cell cycle progression. p21 is primarily regulated at the transcriptional level by several transcription factors, including p53. Previously, we reported that certain members of the E2F family of transcription factors may activate p21 transcription via a p53-independent mechanism. To further elucidate the consequences of E2F-1-regulated induction of p21, we developed cell lines with a tamoxifen-dependent form of E2F-1. We confirmed direct interaction of E2F-1 with the proximal region of the p21 promoter. Interestingly, elevated E2F-1 activity was sufficient to arrest a substantial subset of cells in S phase and this effect was correlated to and dependent on the induction of p21 protein. Since E2F proteins control genes required for cell cycle progression and are activated by various oncogenic events, we believe that the p21-dependent arrest described in this report represents an additional mechanism that guards against unrestricted cell proliferation.

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Acknowledgements

This work was supported by IDPH Grant (ALG), NIH Grant CA91146-01A1 (ALG) and NIH Grant DK48836 (ALT).

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Authors and Affiliations

  1. Department of Medicine, University of Illinois at Chicago, Chicago, USA

    Senthil K Radhakrishnan, Feridoon Najmabadi & Andrei L Gartel

  2. Department of Biochemistry and Molecular Genetics, University of Illinois at Chicago, Chicago, USA

    Claudine S Feliciano, Andrea Haegebarth & Angela L Tyner

  3. Department of Molecular Biology, Lerner Research Institute, Cleveland Clinic Foundation, USA

    Eugene S Kandel

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  1. Senthil K Radhakrishnan
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  2. Claudine S Feliciano
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  6. Angela L Tyner
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Correspondence to Andrei L Gartel.

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Radhakrishnan, S., Feliciano, C., Najmabadi, F. et al. Constitutive expression of E2F-1 leads to p21-dependent cell cycle arrest in S phase of the cell cycle. Oncogene 23, 4173–4176 (2004). https://doi.org/10.1038/sj.onc.1207571

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