W. Zwerschke et al., IDENTIFICATION OF DOMAINS REQUIRED FOR TRANSCRIPTIONAL ACTIVATION ANDPROTEIN DIMERIZATION IN THE HUMAN PAPILLOMAVIRUS TYPE-16 E7 PROTEIN, Oncogene, 12(1), 1996, pp. 213-220
To analyse the potential of the E7 oncogene of HPV-16 to activate tran
scription, we constructed hybrid proteins containing various portions
of the HPV-16 E7 protein fused to the DNA binding region of the bacter
ial LexA repressor. We found that full length HPV-16 E7 is capable to
mediate activation of two different reporter genes, which carry LexA b
inding sites in their promoters. In contrast, E7 from HPV-11, a low-ri
sk type papillomavirus, was unable to activate transcription, when ana
lysed in the same assay. Mutations in the transforming domains of HPV-
16 E7 did not affect the ability of the protein to activate transcript
ion, indicating that it represents a novel function of the oncoprotein
, which is not sensitive to any known inactivating mutations. Analysis
of E7 subdomains revealed that the N-terminal part of HPV-16 E7 retai
ns the capacity to activate transcription. A second trans-activation d
omain is located in the C-terminal part of E7; however, in the context
of the full length E7 protein this activity is blocked by an adjacent
domain. These results reveal a second pathway for transcriptional act
ivation by HPV-16 E7, independent of its interaction with pRB-E2F comp
lexes. Using the E7-LexA hybrid proteins, it is shown that E7 can form
homodimers and this property involves a zinc finger structure in the
C-terminal part of the protein, partially overlapping with the domain
that negatively regulates transcriptional activation by E7.