E7 proteins of four groups of human papillomaviruses, irrespective of their tissue tropism or cancer association, possess the ability to transactivate transcriptional promoters E2F site dependently.
In an experimental system in which an expression vector including the E7 gene of a given human papillomavirus (HPV), together with a luciferase reporter plasmid including the adenovirus E2 (Ad E2) promoter, was transiently transfected into cultured mouse NIH3T3 fibroblastic cells, we obtained the signal indicating that E7 proteins of HPV type 5, 12, 14, 20, 21, 25, and 47, which are associated with epidermodysplasia verruciformis (EV), can transactivate the Ad E2 promoter, as previously reported for E7 proteins of other HPVs. Because the underlying mechanism of the transactivation had not been analyzed, except for transactivation by E7 gene of cervical cancer-associated HPV-16, we compared the E7 genes of representatives of three other groups of HPVs (HPV-1, -11, and -47) with that of HPV-16 with regard to their transactivating activity toward artificially constructed promoters. The experiment with a shortened AdE2 promoter carrying only the E2F sites and TATA box provided evidence that all four E7 proteins can transactivate the shortened promoter and that this phenomenon is E2F site dependent. Further experiments with the reporter gene constructs carrying basal promoters or more complex forms with or without linked E2F sites, (a) confirmed previous finding by others that in cells producing no transactivator, the transcriptional level from promoters linked to E2F sites is rather repressed in comparison with the level of the corresponding promoters that are not linked to the E2F sites, and (b) demonstrated, for the first time, that in cells expected to produce the E7 protein of any one of the four HPVs, transcription from the promoter linked to the E2F sites was released from repression. In other words, the present results reveal that E7 proteins of any of the four HPVs can remove the E2F site-dependent repression, probably by modulating E2F complexes from repressing forms to activating ones.
Hiraiwa
A
A
Laboratory of Viral Oncology, Aichi Cancer Center, Nagoya, Japan.
Kiyono
T
T
Suzuki
S
S
Ohashi
M
M
Ishibashi
M
M
D001483:Base Sequence; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D008969:Molecular Sequence Data; D009856:Oncogene Proteins, Viral / Q000235:genetics*; D027383:Papillomaviridae / Q000235:genetics*; D050725:Papillomavirus E7 Proteins; D011401:Promoter Regions, Genetic / Q000235:genetics*; D056465:Retinoblastoma-Binding Protein 1; D050680:Transcription Factor DP1; D014157:Transcription Factors / Q000235:genetics*; D015533:Transcriptional Activation / Q000235:genetics*; D014162:Transfection
C533431:Arid4a protein, mouse; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D056465:Retinoblastoma-Binding Protein 1; D050680:Transcription Factor DP1; D014157:Transcription Factors; C059731:oncogene protein E7, Human papillomavirus type 16