Human papillomavirus type 16 (HPV-16) is strongly associated with the development of cervical cancer. The E6 and E7 proteins from HPV-16 possess several functions that contribute to oncogenesis. HPV-16 E7 is known to bind and inactivate the retinoblastoma tumor suppressor protein. Expression of E7 alone extends the life span of newborn foreskin epithelial cells about twofold, whereas expression of E6 and E7 together can result in cellular immortalization without a significant crisis. HPV-16 E6 functions in the activation of telomerase and the targeting of p53 for ubiquitin-mediated degradation. E6 is known to alter the expression of several cellular genes by both p53-dependent and -independent mechanisms. Several cellular transcription factors (such as c-Myc, Sp1 and WT1) have been reported to be involved in telomerase regulation in either a cell-specific or -nonspecific manner. We propose that HPV-16 E6 activates telomerase through the upregulation of a cellular telomerase activator or the downregulation of a cellular telomerase repressor. To identify cellular genes involved in the activation of telomerase by E6 we have performed an oligonucleotide array analysis of messenger RNA from cells expressing E7 and either wild-type or mutant E6. The E6 mutants we are studying differentially activate telomerse and target p53. Array analysis of these mutants will help us identify changes in gene expression specifically associated with telomerase activation.