The E7 proteins of the nononcogenic human papillomavirus type 6b (HPV-6b) and of the oncogenic HPV-16 differ in retinoblastoma protein binding and other properties.
The E7 early viral protein of the oncogenic human papillomavirus type 16 (HPV-16) has been strongly implicated in the maintenance of the malignant phenotype in cervical cancers and cancer-derived cell lines. HPV-16 E7 is a nuclear phosphoprotein that can cooperate with ras to transform baby rat kidney cells, transactivates the adenovirus E2 promoter, and binds to the retinoblastoma (RB) protein. The E7 phosphoprotein of the nononcogenic HPV-6b, which is generally associated with benign genital warts, is similar to the HPV-16 E7 in amino acid sequence but differs dramatically in migration in sodium dodecyl sulfate-polyacrylamide gels, sedimentation in nondenaturing glycerol gradients, and the ability to bind the RB protein. Our results indicate that the RB protein preferentially binds the phosphorylated form of HPV-6b E7, which comprises a minor fraction of the total E7 expressed in transiently transfected COS-7 cells. These characteristics may help to explain the difference in the oncogenic potential of the oncogenic and nononcogenic types of genital papillomaviruses.
Gage
J R
JR
Department of Microbiology and Immunology, School of Medicine, University of California, Los Angeles 90024.
Meyers
C
C
Wettstein
F O
FO
D000595:Amino Acid Sequence; D000596:Amino Acids / Q000032:analysis; D000818:Animals; D002460:Cell Line; D005822:Genetic Vectors; D006801:Humans; D007106:Immune Sera; D008969:Molecular Sequence Data; D008970:Molecular Weight; D009856:Oncogene Proteins, Viral / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D027383:Papillomaviridae / Q000235:genetics* / Q000378:metabolism / Q000472:pathogenicity; D010750:Phosphoproteins / Q000378:metabolism*; D010766:Phosphorylation; D011485:Protein Binding; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000378:metabolism; D016160:Retinoblastoma Protein; D012689:Sequence Homology, Nucleic Acid; D013045:Species Specificity; D014162:Transfection
D000596:Amino Acids; D007106:Immune Sera; D009856:Oncogene Proteins, Viral; D010750:Phosphoproteins; D011993:Recombinant Fusion Proteins; D016160:Retinoblastoma Protein