The human papillomavirus type 16 E7 protein complements adenovirus type 5 E1A amino-terminus-dependent transactivation of adenovirus type 5 early genes and increases ATF and Oct-1 DNA binding activity.
We have previously shown that conserved region 1 (CR1) of the adenovirus type 5 (Ad5) E1A protein synergizes with CR3 in the transactivation of Ad5 early genes (H.K. Wong and E. B. Ziff, J. Virol. 68:4910-4920, 1994). CR1 lies within the E1A amino terminus and binds host regulatory proteins such as the RB protein, p107, p130, and p300. Since simian virus 40 (SV40) large T antigen and human papillomavirus type 16 (HPV16) E7 protein also bind host regulatory factors, we investigated whether these viral proteins can complement E1A mutants which are defective in early gene activation. We show that the HPV16 E7 protein but not SV40 T antigen can complement mutations in the Ad5 E1A CR1 in the transactivation of viral early promoters. The inability of SV40 T antigen to complement suggests that RB binding on its own is not sufficient for early promoter transactivation by the E1A amino terminus. Nuclear runoff assays show that complementation by HPV16 E7 restores the ability of the E1A mutants to stimulate early gene expression at the level of transcription. Furthermore, nuclear extracts from the E7-transformed cells show increased binding activity of ATF and Oct-1, factors that can recognize the elements of Ad5 early genes, consistent with gene activation by E1A and E7 at the transcriptional level.
Department of Biochemistry, Howard Hughes Medical Institute, Kaplan Cancer Center, New York University School of Medicine, New York 10016, USA.
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Wong
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Ziff
D016475:3T3 Cells; D051696:Activating Transcription Factors; D017500:Adenovirus E1A Proteins / Q000378:metabolism*; D000260:Adenoviruses, Human / Q000235:genetics* / Q000254:growth & development; D000818:Animals; D001483:Base Sequence; D001798:Blood Proteins / Q000378:metabolism*; D004279:DNA, Viral / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism*; D015967:Gene Expression Regulation, Viral; D005814:Genes, Viral; D005816:Genetic Complementation Test; D006367:HeLa Cells; D051863:Host Cell Factor C1; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D050811:Octamer Transcription Factor-1; D009856:Oncogene Proteins, Viral / Q000235:genetics / Q000378:metabolism*; D050725:Papillomavirus E7 Proteins; D011485:Protein Binding; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism; D016160:Retinoblastoma Protein / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism*; D015533:Transcriptional Activation; D014407:Tumor Cells, Cultured
D051696:Activating Transcription Factors; D017500:Adenovirus E1A Proteins; D001798:Blood Proteins; D004279:DNA, Viral; D004268:DNA-Binding Proteins; C497692:HCFC1 protein, human; C497693:Hcfc1 protein, mouse; D051863:Host Cell Factor C1; D050811:Octamer Transcription Factor-1; D009856:Oncogene Proteins, Viral; C494165:POU2F1 protein, human; D050725:Papillomavirus E7 Proteins; C494166:Pou2f1 protein, mouse; D016755:Proto-Oncogene Proteins c-jun; D016160:Retinoblastoma Protein; D014157:Transcription Factors; C059731:oncogene protein E7, Human papillomavirus type 16