Skin human papillomavirus type 38 alters p53 functions by accumulation of ΔNp73

Rosita Accardi, Wen Dong, Anouk Smet, Rutao Cui, Agnes Hautefeuille, Anne Sophie Gabet, Bakary S. Sylla, Lutz Gissmann, Pierre Hainaut, Massimo Tommasino

    Research output: Contribution to journalArticle

    85 Scopus citations

    Abstract

    The E6 and E7 of the cutaneous human papillomavirus (HPV) type 38 immortalize primary human keratinocytes, an event normally associated with the inactivation of pathways controlled by the tumour suppressor p53. Here, we show for the first time that HPV38 alters p53 functions. Expression of HPV38 E6 and E7 in human keratinocytes or in the skin of transgenic mice induces stabilization of wild-type p53. This selectively activates the transcription of ΔNp73, an isoform of the p53-related protein p73, which in turn inhibits the capacity of p53 to induce the transcription of genes involved in growth suppression and apoptosis. ΔNp73 downregulation by an antisense oligonucleotide leads to transcriptional re-activation of p53-regulated genes and apoptosis. Our findings illustrate a novel mechanism of the alteration of p53 function that is mediated by a cutaneous HPV type and support the role of HPV38 and ΔNp73 in human carcinogenesis.

    Original languageEnglish (US)
    Pages (from-to)334-340
    Number of pages7
    JournalEMBO reports
    Volume7
    Issue number3
    DOIs
    StatePublished - Mar 1 2006

    Keywords

    • Cutaneous HPV38
    • E6 and E7
    • p53
    • ΔNp73

    ASJC Scopus subject areas

    • Biochemistry
    • Molecular Biology
    • Genetics

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  • Cite this

    Accardi, R., Dong, W., Smet, A., Cui, R., Hautefeuille, A., Gabet, A. S., Sylla, B. S., Gissmann, L., Hainaut, P., & Tommasino, M. (2006). Skin human papillomavirus type 38 alters p53 functions by accumulation of ΔNp73. EMBO reports, 7(3), 334-340. https://doi.org/10.1038/sj.embor.7400615