FUNCTIONAL-STUDIES OF E7 PROTEINS FROM DIFFERENT HPV TYPES

We have performed comparative studies on the E7 proteins from malignan t and non-malignant Human Papillomavirus types (HPV 1, 6, 11, 16, 18, 33). GST/E7 fusion proteins from all these HPV types associate with Rb 1, p107 and the cyclin A/CDK2 complex. As has been shown for Rb1, the association with p107 and Cyclin A was weaker for the 'low risk' HPV6 and 11 E7 proteins as compared to 'high risk' HPV16, 18 and 33 E7 prot eins. In contrast the E7 protein of the benign type HPV1 bound Rb1, p1 07 and cyclin A with the same affinity as the 'high risk' E7 proteins. The affinities of the E7/Rb1 interaction have been confirmed in vivo by the 'two hybrid' method in the yeast Saccharomyces cerevisiae. Alth ough HPV1 E7 showed the same affinity in vitro and in vivo for Rb1 as the high risk HPV E7s, it did not have the ability to activate the E2F -1 transcription factor inhibited by Rb1, nor did it have any transfor ming activity when coexpressed with activated ras in primary rodent ce lls.