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Differential Enhancement of a Cutaneous HPV Promoter by ΔNP63α, JUN and Mutant p53

Cell Cycle 4(5):689 (2005) PMID 20016459 PMCID PMC3149972

The mechanism through which cutaneous papillomaviruses induce lesions is largely unknown. Ectopic expression of the ΔNP63α isoform highly increased the viral promoter activity. The co-expression of c-Jun mediated and increased the ΔNP63α activity by binding to the AP-1 site in an enhancer region of the HPV 20 URR. This strong activation by ΔNP63α is diminished in the presence of wtp53 and abolished by the simultaneous expression of “hotspot” mutant p53 R248W. We demonstrate that c-Jun is responsible for the viral promoter activation through its direct interaction with both ΔNP63α and wtp53. The down-regulation by p53 mutant R248W is accompanied by reduced protein levels of ΔNP63α and phosphorylated c-Jun. The data presented in this study provide insight into a possible mechanism through which these cellular proteins may modulate a cutaneous papillomavirus genome to induce viral replication, latent infection or malignant trasnformation.

DOI: 10.4161/cc.4.5.1653