Although E6 and E7 themselves possess intrinsic trans-activation capacity on their homologous promoters (14, 52), constitutive expression of E6 or E7 in immortalized or malignantly transformed human keratinocytes is mainly dependent on the availability of a defined set of transcription factors derived from the infected host cell. AP-1, for example, normally consisting of a heterodimer between c-Fos and c-Jun (for a review, see reference 4), seems to play a central role in transcriptional regulation of viral oncogene expression, since point mutations of the corresponding consensus sequences within the upstream regulatory region (URR) of HPV-16 or HPV-18 almost completely abolish the expression of URR-driven reporter plasmids in transient transfection assays Recent studies have shown that trans-activation and the DNA-binding affinity of AP-1 (1, 44) as well as that of other transcription factors such as NF-B (65, 78) or p53 (29) can be modulated not only via posttranslational modifications such as phosphorylation or dephosphorylation (for a review, see ref- erence 31) but also by alterations of the intracellular redox status. This can be achieved by certain cytokines, which are able to induce a prooxidant state within the cell by generating reactive oxygen intermediates (ROIs) Similar prooxidant conditions can also be generated either by exposing cells directly to hydrogen peroxide (40) or by genotoxic stress after UV irradiation (60), leading in both cases to the activation of AP-1 (74) and NF-B (44). While such intracellular redox changes are normally counterbalanced by antioxidant enzymes like Cu-Zn-superoxide dismutases (48) or oxidoreductases such as thioredoxin In a previous study, we showed that tumor necrosis factor alpha-induced transcription of a chemokine gene encoding monocyte chemoattractant protein 1 (MCP-1) could be completely abrogated when nonmalignant HPV-positive cells were incubated with PDTC prior to cytokine addition (57). Consistent with the aforementioned model of redox modulation of specific genes, detailed promoter analysis has revealed that NF-B and AP-1 are indeed the predominant transcription factors involved in the regulation of this particular chemokine Since AP-1 is also a central transcription factor for efficien
