Biochemical and biological differences between E7 oncoproteins of the high- and low-risk human papillomavirus types are determined by amino-terminal sequences.
Differences in the biological characteristics of the high-risk human papillomavirus type 16 (HPV-16) and the low-risk HPV-6 E7 proteins were analyzed and shown to correlate with certain biochemical properties. To ascertain which region of E7 conferred these properties, chimeric E7 genes were constructed by the exchange of the amino and carboxyl coding halves of the HPV-6 and HPV-16 E7 genes. The amino-terminal half of E7 determined the affinity for binding to the retinoblastoma protein pRB, the transformation properties, and the ability to abrogate transforming growth factor beta-mediated repression of the c-myc promoter. This region of E7 is therefore responsible for the biological and biochemical differences between the E7 proteins of the low-risk and the high-risk HPVs and consequently is one of the critical determinants distinguishing these two groups of viruses. Transcriptional transactivation of the adenovirus E2 promoter, in contrast, was a property shared by E7 proteins of both low-risk and high-risk HPVs.
Münger
K
K
Laboratory of Tumor Virus Biology, National Cancer Institute, Bethesda, Maryland 20892.
Yee
C L
CL
Phelps
W C
WC
Pietenpol
J A
JA
Moses
H L
HL
Howley
P M
PM
D017456:Adenovirus Early Proteins; D000595:Amino Acid Sequence; D000818:Animals; D002472:Cell Transformation, Viral; D003001:Cloning, Molecular; D006224:Cricetinae; D006801:Humans; D066298:In Vitro Techniques; D009856:Oncogene Proteins, Viral / Q000737:chemistry* / Q000235:genetics; D027383:Papillomaviridae / Q000235:genetics / Q000472:pathogenicity*; D050725:Papillomavirus E7 Proteins; D011401:Promoter Regions, Genetic; D016283:Proto-Oncogene Proteins p21(ras) / Q000502:physiology; D011993:Recombinant Fusion Proteins; D013045:Species Specificity; D013329:Structure-Activity Relationship; D015533:Transcriptional Activation; D016212:Transforming Growth Factor beta / Q000502:physiology
D017456:Adenovirus Early Proteins; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D011993:Recombinant Fusion Proteins; D016212:Transforming Growth Factor beta; C059731:oncogene protein E7, Human papillomavirus type 16; C501009:HRAS protein, human; D016283:Proto-Oncogene Proteins p21(ras)