Chk2 activates E2F-1 in response to DNA damage

Stevenson, C., Smith, L. and La Thangue, N.B. (2003) Chk2 activates E2F-1 in response to DNA damage. Nature Cell Biology, 5, pp. 401-409. (doi: 10.1038/ncb974)

Abstract

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.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Stevenson, Mr Craig and Smith, Mrs Linda
• Authors: Stevenson, C., Smith, L., and La Thangue, N.B.
• Subjects: Q Science > QR Microbiology
• College/School: College of Medical Veterinary and Life Sciences
• Journal Name: Nature Cell Biology
• ISSN: 1465-7392