E2F-1 induces the stabilization of p53 but blocks p53-mediated transactivation.

Nip J, Strom DK, Eischen CM, Cleveland JL, Zambetti GP, Hiebert SW
Oncogene. 2001 20 (8): 910-20

PMID: 11314026 · DOI:10.1038/sj.onc.1204171

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.

MeSH Terms (19)

Animals Binding Sites Carrier Proteins Cell Cycle Cell Cycle Proteins Cells, Cultured DNA-Binding Proteins E2F1 Transcription Factor E2F Transcription Factors Mice Protein Binding Protein Processing, Post-Translational Proteins Retinoblastoma-Binding Protein 1 Transcriptional Activation Transcription Factor DP1 Transcription Factors Tumor Suppressor Protein p14ARF Tumor Suppressor Protein p53

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