Research Output
Chk2 activates E2F-1 in response to DNA damage
  The E2F-1 transcription factor is regulated during cell cycle progression and induced by cellular stress, such as DNA damage. We report that checkpoint kinase 2 (Chk2) regulates E2F-1 activity in response to the DNA-damaging agent etoposide. A Chk2 consensus phosphorylation site in E2F-1 is phosphorylated in response to DNA damage, resulting in protein stabilization, increased half-life, transcriptional activation and localization of phosphorylated E2F-1 to discrete nuclear structures. Expression of a dominant-negative Chk2 mutant blocks induction of E2F-1 and prevents E2F-1-dependent apoptosis. Moreover, E2F-1 is resistant to induction by etoposide in tumour cells expressing mutant chk2. Therefore, Chk2 phosphorylates and activates E2F-1 in response to DNA damage, resulting in apoptosis. These results suggest a role for E2F-1 in checkpoint control and provide a plausible explanation for the tumour suppressor activity of E2F-1.

  • Type:


  • Date:

    22 April 2003

  • Publication Status:


  • Publisher

    Springer Nature

  • DOI:


  • Cross Ref:


  • ISSN:


  • Library of Congress:

    QH301 Biology

  • Dewey Decimal Classification:

    571 Physiology & related subjects

  • Funders:

    Medical Research Council; Historic Funder (pre-Worktribe)


Stevens, C., Smith, L., & La Thangue, N. B. (2003). Chk2 activates E2F-1 in response to DNA damage. Nature Cell Biology, 5(5), 401-409.



Cell Biology

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