Cookies on this website

We use cookies to ensure that we give you the best experience on our website. If you click 'Accept all cookies' we'll assume that you are happy to receive all cookies and you won't see this message again. If you click 'Reject all non-essential cookies' only necessary cookies providing core functionality such as security, network management, and accessibility will be enabled. Click 'Find out more' for information on how to change your cookie settings.

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.

Original publication

DOI

10.1038/ncb974

Type

Journal article

Journal

Nat Cell Biol

Publication Date

05/2003

Volume

5

Pages

401 - 409

Keywords

Apoptosis, Cell Cycle, Cell Cycle Proteins, Cell Nucleus, Checkpoint Kinase 2, DNA Damage, DNA-Binding Proteins, E2F Transcription Factors, E2F1 Transcription Factor, Etoposide, Eukaryotic Cells, Gene Expression Regulation, Neoplastic, Humans, Mutation, Nucleic Acid Synthesis Inhibitors, Phosphorylation, Protein Kinases, Protein-Serine-Threonine Kinases, Serine, Signal Transduction, Transcription Factors, Transcriptional Activation, Tumor Cells, Cultured, Tumor Suppressor Proteins