p73α expression induces both accumulation and activation of wt-p53 independent of the p73α transcriptional activity

Francesc Miro-Mur, Anne Meiller, Hedi Haddada, Evelyne May

    Research output: Contribution to journalArticleResearchpeer-review

    11 Citations (Scopus)

    Abstract

    The p53 tumor suppressor gene belongs to a multigene family that includes two paralogues, p63 and p73. p73α has common activities with p53, such as DNA binding and transactivation, and can thus activate the transcription of p53-responsive genes. Using the adenoviral system, we report that an overexpression of either wt-p73α or one of the two transcriptional inactive mutants, ΔNp73α or p73αR292H, induces an accumulation of the endogenous wt-p53 expressed in the three transformed cell lines, SK-N-SH, MCF-7 and U-2OS, without stimulating the p53 gene transcription. p73-mediated accumulation of p53 protein coincides with an increase of p53-target gene expression in cells expressing either wt-p73α or the transcriptional inactive mutant p73αR292H, but not ΔNp73α that encodes a dominant-negative mutant of both p73 and p53. The fact that an ectopic expression of p73αR292H leads to both accumulation of p53 and stimulation of p53 target gene expression strongly suggests that p73α is able to induce activation of p53. This was confirmed by showing that p73αR292H no longer stimulated Waf1/p21 expression in MCF7/R-A1 cells that expressed a transcriptional inactive mutant of p53. We thus conclude that p73α protein was able to both stabilize and activate wt-p53 protein, independent of the p73α transcriptional activity.
    Original languageEnglish
    Pages (from-to)5451-5456
    JournalOncogene
    Volume22
    Issue number35
    DOIs
    Publication statusPublished - 21 Aug 2003

    Keywords

    • p53
    • p73α
    • p73αR292H
    • Protein stability
    • Recombinant adenovirus
    • Transcriptional activity

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