MODULATION OF TRANSCRIPTIONAL REGULATORY PROPERTIES OF P53 BY HPV-E6

The E6 protein encoded by human papillomavirus type 16 (HPV16), a geni tal virus with oncogenic potential, can target cellular p53 for rapid degradation following the formation of a complex including the two pro teins. Some studies suggest that the E6 proteins encoded by HPV6 and 1 1, viral types which are normally limited to benign lesions, may also interact with p53, although the association is weaker than that seen w ith HPV16 E6. The present study demonstrates that E6 proteins from HPV 16 and HPV6 can modulate the transcriptional regulatory functions of p 53 in several cell types. A series of E6 mutants was used to show that association between E6 and p53 is necessary for this activity and tha t E6 proteins which retain the ability to associate with p53 but show no detectable degradation activity in vitro can, to some extent, abrog ate p53 mediated transcriptional trans-regulation. This activity is au gmented, however, by the ability of the E6 protein to target bound p53 for rapid degradation. These results suggest that some degree of modu lation of p53 function is necessary in the normal viral life cycle but also demonstrate a correlation between the efficiency of this activit y and oncogenic potential of the virus.