Differential enhancement of a cutaneous HPV promoter by DeltaNP63alpha, Jun and mutant p53.
The mechanism through which cutaneous papillomaviruses induce lesions is largely unknown. Ectopic expression of the DeltaNp63alpha isoform highly increased the viral promoter activity. The co-expression of c-Jun mediated and increased the DeltaNp63alpha activity by binding to the AP-1 site in an enhancer region of the HPV 20 URR. This strong activation by DeltaNp63alpha is diminished in the presence of wtp53 and abolished by the simultaneous expression of "hot-spot" mutant p53 R248W. We demonstrate that c-Jun is responsible for the viral promoter activation through its direct interaction with both DeltaNp63alpha and wtp53. The downregulation by p53 mutant R248W is accompanied by reduced protein levels of DeltaNp63alpha 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 transformation.
Fei
Jian-Wei
JW
Division for the Characterization of Tumorviruses, Deutsches Krebsforschungszentrum, Im Neuenheimer Feld 242, 69120 Heidelberg, Germany.
Wei
Quan-Xiang
QX
Angel
Peter
P
de Villiers
Ethel-Michele
EM
D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic; D004279:DNA, Viral / Q000235:genetics / Q000502:physiology; D004268:DNA-Binding Proteins; D015536:Down-Regulation; D015967:Gene Expression Regulation, Viral; D016147:Genes, Tumor Suppressor / Q000502:physiology*; D005814:Genes, Viral; D006801:Humans; D009154:Mutation; D027383:Papillomaviridae / Q000235:genetics* / Q000502:physiology; D010750:Phosphoproteins / Q000235:genetics / Q000502:physiology*; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D020033:Protein Isoforms; D016755:Proto-Oncogene Proteins c-jun / Q000235:genetics / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015534:Trans-Activators / Q000235:genetics / Q000502:physiology*; D014157:Transcription Factors; D014162:Transfection; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000502:physiology*; D025521:Tumor Suppressor Proteins; D014775:Virus Activation; D014779:Virus Replication / Q000235:genetics
D004279:DNA, Viral; D004268:DNA-Binding Proteins; D010750:Phosphoproteins; D020033:Protein Isoforms; D016755:Proto-Oncogene Proteins c-jun; C495901:TP53 protein, human; C115051:TP63 protein, human; D015534:Trans-Activators; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins