TRANSACTIVATION OF PROTHYMOSIN-ALPHA AND C-MYC PROMOTERS BY HUMAN PAPILLOMAVIRUS TYPE-16 E6 PROTEIN

The human papillomavirus type 16 E6 protein exerts a transforming acti vity through inactivation of tumor suppressor p53. Recently E6 has bee n shown to have additional transforming activities independent of p53. E6 is able to transactivate or repress several specific viral promote rs. However, underlying molecular mechanisms and cellular target genes for the activity are not well understood. Using a differential hybrid ization technique, we identified the prothymosin alpha gene as a cellu lar target of E6 transactivation. E6 was able to transactivate the pro thymosin ru promoter in H358 cells lacking p53 and in C33A cells harbo ring a mutant p53 allele. Disruption of the E-box in intron 1 of the p rothymosin alpha promoter abolished the responsiveness to E6. Then we determined if E6 up-regulates the expression of Myc, by which the prot hymosin alpha promoter is transactivated through the E-box. We found t hat E6 is also able to transactivate the c-myc promoter in H358 cells and in C33A cells. These results suggest that E6 is able to transactiv ate the c-myc promoter independently of p53,and that the prothymosin a lpha promoter is subsequently transactivated by Myc. (C) 1997 Academic Press