Analysis of trans activation by human papillomavirus type 16 E7 and adenovirus 12S E1A suggests a common mechanism.
The human papillomavirus E7 gene product is an oncoprotein with properties similar to those of the adenovirus E1A proteins. The human papillomavirus E7 proteins possess substantial amino acid sequence similarity to portions of conserved regions 1 and 2 of E1A, and the human papillomavirus type 16 E7 protein trans-activates the adenovirus E2 early promoter. Analysis of point mutations in the E2 promoter indicated that the E2F recognition sites were critical to E7 stimulation. In contrast to the activation of the E2 promoter, E7 could not trans-activate various other E1A-inducible promoters. Although the promoter specificity for E7 differs from that of 13S E1A trans activation, it is very similar to activation by the E1A 12S product. Moreover, analysis of the E7 protein has suggested that amino acid sequences critical for trans activation include those shared with E1A within conserved region 2. Biochemical studies demonstrate that the E7 protein, like the 12S E1A product, can alter the interaction of cellular factors with the E2F transcription factor. We therefore conclude that E7 trans activation is functionally related to that mediated by the 12S E1A product.
Phelps
W C
WC
Division of Virology, Burroughs Wellcome Co., Research Triangle Park, North Carolina 27709.
Bagchi
S
S
Barnes
J A
JA
Raychaudhuri
P
P
Kraus
V
V
Münger
K
K
Howley
P M
PM
Nevins
J R
JR
D017456:Adenovirus Early Proteins; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D002872:Chromosome Deletion; D005814:Genes, Viral; D005982:Glutathione Transferase / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides; D009856:Oncogene Proteins, Viral / Q000235:genetics* / Q000378:metabolism; D009857:Oncogenes; D050725:Papillomavirus E7 Proteins; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic; D011505:Protein-Tyrosine Kinases / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012689:Sequence Homology, Nucleic Acid; D014157:Transcription Factors / Q000235:genetics*; D015533:Transcriptional Activation
D017456:Adenovirus Early Proteins; D009838:Oligodeoxyribonucleotides; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D011993:Recombinant Fusion Proteins; D014157:Transcription Factors; C059731:oncogene protein E7, Human papillomavirus type 16; D005982:Glutathione Transferase; D011505:Protein-Tyrosine Kinases