Transformation by the human papillomavirus (HPV) early gene products, E6 and E7, 
involves their interaction with cellular proteins p53 and Rb. Using glutathione 
S-transferase (GST) fusion proteins, we found that HPV E6 bound human p53 and 
that the relative efficiency of binding varied such that the GST-HPV type 16 E6 
(16E6) protein bound p53 with highest affinity, followed by GST-31E6, GST-18E6, 
and GST-11E6. The GST-E6 fusion proteins were sufficient for binding p53 
purified from a baculovirus expression system as well as in vitro translation 
sources, while no association was observed with GST-18E7 or a GST-16E6 mutant 
bearing a five-amino-acid deletion in E6. When the site-specific DNA binding 
activity of p53 was examined in the presence of GST-E6 proteins, an inhibition 
of DNA binding was observed. The degree of inhibition correlated with the 
relative affinity of different E6 proteins for p53; thus, GST-16E6 was the most 
potent inhibitor of p53 DNA binding activity, and GST-11E6 was the least 
effective. Prevention of p53 DNA binding is likely to play a role in the 
abrogation of the transcriptional activity of p53 by HPV E6 and provides a 
further mechanism for E6 disruption of p53 growth suppressor function in 
addition to its role in directing specific degradation of p53 through the 
ubiquitin-mediated pathway. The variation in inhibition of DNA binding seen with 
the various E6 proteins may thus contribute to the differences in oncogenic 
potential seen among the HPV types.