Wild-type p53 is a nuclear phosphoprotein that inhibits cell prolifera
tion and represses transcriptionally most TATA box-containing promoter
s in transformed or tumor-derived cell lines. This study demonstrates
that p53 alters transcription of the long control region (LCR) of huma
n papillomavirus type 18 (HPV-18), Wild-type and mutant p53 143(Val to
Ala) repressed the HPV-18 LCR promoter in normal human keratinocytes,
the natural host cell for HPV infections. Repression by wild-type p53
was also observed in C-33A cells and in an HPV-16-immortalized cell l
ine with an inducible wild-type p53, However, when C-33A cells were co
transfected with the HPV-18 LCR and mutant 143(Val to Ala), repression
did not occur. Mutant p53 135(Cys to Ser) did not induce repression i
n either normal human keratinocytes or in the C-33A line; although lik
e 143(Val to Ala), it is thought to affect the DNA binding activity of
the wild-type protein. The ability of mutant p53 143(Val to Ala) to i
nactivate the HPV early promoter in normal cells (by approximately 60%
reduction) suggests that this mutant may be able to associate with wi
ld-type p53 and interact with TATA box-binding proteins, Therefore, th
ese results demonstrate that the transcriptional activities of p53 mut
ants may be dependent upon the cell type assayed and the form of its e
ndogenous p53, Furthermore, normal human keratinocytes represent an al
ternative model for determining the activities of p53 mutants.