E2F-1 induces the stabilization of p53 but blocks p53-mediated transactivation
- 22 February 2001
- journal article
- Published by Springer Science and Business Media LLC in Oncogene
- Vol. 20 (8), 910-920
- https://doi.org/10.1038/sj.onc.1204171
Abstract
E2F-1 induces p53 accumulation and E2F-1 and p53 form a physical complex, which affects the ability of E2F-1 to activate transcription. We mapped the domains on E2F-1 that interact with p53 and found two p53-binding domains. To understand the functional consequences of the E2F-1/p53 association on p53 activities we identified the domains of E2F-1 that were responsible for the accumulation of p53. Unexpectedly, we found that the E2F-1 transactivation domain was dispensable for p53 induction. By contrast, further deletion of the DP-1 interaction/'marked' box domain eliminated p53 accumulation. Radiolabeling pulse/chase analysis demonstrated that E2F-1 caused post-translational stabilization of p53. Although E2F-1 caused the stabilization of p53, E2F-1 expression impaired p53-dependent transactivation. Thus, the E2F-1 : p53 interaction may provide a checkpoint function to inactivate overactive E2F-1, but the association may also inactivate p53 transactivation to allow cell cycle progression.Keywords
This publication has 72 references indexed in Scilit:
- The E1B 19K protein blocks apoptosis by interacting with and inhibiting the p53-inducible and death-promoting Bax protein.Genes & Development, 1996
- Transcriptional control by E2FSeminars in Cancer Biology, 1995
- Differential regulation of E2F transactivation by cyclin/cdk2 complexes.Genes & Development, 1994
- Negative regulation of the growth-promoting transcription factor E2F-1 by a stably bound cyclin A-dependent protein kinaseCell, 1994
- Several hydrophobic amino acids in the p53 amino-terminal domain are required for transcriptional activation, binding to mdm-2 and the adenovirus 5 E1B 55-kD protein.Genes & Development, 1994
- A new regulatory motif in cell-cycle control causing specific inhibition of cyclin D/CDK4Nature, 1993
- Retinoblastoma protein switches the E2F site from positive to negative elementNature, 1992
- p53, guardian of the genomeNature, 1992
- The mdm-2 oncogene product forms a complex with the p53 protein and inhibits p53-mediated transactivationCell, 1992
- The interaction of RB with E2F coincides with an inhibition of the transcriptional activity of E2F.Genes & Development, 1992