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TAp63α indirectly regulates a cutaneous HPV promoter through complex formation with Jun family members

Oncogene volume 25, pages 3914–3923 (2006)Cite this article

Abstract

The p63α isoforms of the p53 family have been demonstrated to play a crucial role in the development and differentiation of the skin. We show that expression of the TAp63α isoform leads to an upregulation of the cutaneous papillomavirus HPV 20 promoter, which is increased at least three-fold when c-Jun is co-expressed, in contrast to a minimal increase in activity in the presence of c-Jun alone. Co-expression of TAp63α with JunB or JunD, respectively, and in combination, leads to a reduction in the viral promoter activation measured by the expression of TAp63α alone. JunB and JunD also inhibits the additive effect exerted on the TAp63α activation by c-Jun. Co-immunoprecipitation assays demonstrate a complex formation of c-Jun, JunB and JunD with TAp63α through the SAM domain mediating protein–protein interactions, which is characteristic for p63α. Co-expression of p53 mutant R248W not only downregulates the differential modulation of the viral promoter by TAp63α alone and in the presence of the Jun family members, but leads to a reduction in the protein levels of the overexpressed c-Jun, JunB, JunD, as well as TAp63α. This model system provides insight into yet unknown pathways through which TAp63α and Jun may cooperate in the pathogenesis of HPV associated cutaneous lesions.

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Acknowledgements

We thank Bianca Berdel and Karin Gunst for excellent technical assistance. We thank Drs V DiLaurenzi and G Melino for the TAp63α construct. This study was in part supported by the Bundesministerium für Gesundheit, Berlin.

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Authors and Affiliations

  1. Division Characterization of Tumorviruses, Deutsches Krebsforschungszentrum, Heidelberg, Germany

    J-W Fei, Q-X Wei & E-M de Villiers

  2. Division of Signal Transduction and Growth Control, Deutsches Krebsforschungszentrum, Heidelberg, Germany

    P Angel

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Correspondence to E-M de Villiers.

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Fei, JW., Angel, P., Wei, QX. et al. TAp63α indirectly regulates a cutaneous HPV promoter through complex formation with Jun family members. Oncogene 25, 3914–3923 (2006). https://doi.org/10.1038/sj.onc.1209420

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