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

• Published in: Cell cycle (Georgetown, Tex.) Vol. 4; no. 5; pp. 689 - 696
• Main Authors: Fei, Jian-Wei, Wei, Quan-Xiang, Angel, Peter, Villiers, Ethel-Michele de
• Format: Journal Article
• Language: English
• Published: Taylor & Francis 02.05.2005
• Subjects: Binding; Biology; Bioscience; Calcium; Cancer; Cell; Cycle; Landes; Organogenesis; Proteins
• ISSN: 1538-4101; 1551-4005
• DOI: 10.4161/cc.4.5.1653

The mechanism through which cutaneous papillomaviruses induce lesions is largelyunknown. Ectopic expression of the ΔNP63α isoform highly increased the viral promoteractivity. The co-expression of c-Jun mediated and increased the ΔNP63α activity by bindingto the AP-1 site in an enhancer region of the HPV 20 URR. This strong activation by ΔNP63αis 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 promoteractivation through its direct interaction with both ΔNP63α and wtp53. The down-regulationby p53 mutant R248W is accompanied by reduced protein levels of ΔNP63α andphosphorylated c-Jun. The data presented in this study provide insight into a possiblemechanism through which these cellular proteins may modulate a cutaneous papillomavirusgenome to induce viral replication, latent infection or malignant trasnformation.