The human papillomavirus type 16 E7 gene product interacts with and trans-activates the AP1 family of transcription factors.
The E7 gene product of human papillomavirus type 16 (HPV16) binds to the retinoblastoma gene product (pRb) and dissociates pRb-E2F complexes. However, the observation that the ability of E7 to bind pRb is not required for the HPV16-induced immortalization of primary keratinocytes prompted a search for other cellular factors bound by E7. Using a glutathione-S-transferase (GST) fusion protein system, we show that E7 complexes with AP1 transcription factors including c-Jun, JunB, JunD and c-Fos. The ability of E7 to complex with c-Jun in vivo is demonstrated by co-immunoprecipitation and the yeast two-hybrid system. An analysis of E7 point mutants in the GST system indicates that the E7 zinc-finger motif, but not the pRb binding domain, is involved in these interactions. Using c-Jun deletion mutants, E7 binding maps between amino acids 224 and 286 of c-Jun. E7 trans-activates c-Jun-induced transcription from a Jun responsive promoter, and this activity correlates with the ability of E7 mutants to bind Jun proteins. Finally, a transcriptionally inactive c-Jun deletion, which can bind E7, interferes with the E7-induced transformation of rat embryo fibroblasts in cooperation with an activated ras, indicating that the Jun-E7 interaction is physiologically relevant and that Jun factors may be targeted in the E7 transformation pathway.
Antinore
M J
MJ
Department of Microbiology and Immunology, University of Rochester, NY 14642, USA.
Birrer
M J
MJ
Patel
D
D
Nader
L
L
McCance
D J
DJ
D000818:Animals; D002472:Cell Transformation, Viral; D002478:Cells, Cultured; D006801:Humans; D066298:In Vitro Techniques; D009856:Oncogene Proteins, Viral / Q000235:genetics* / Q000378:metabolism*; D027383:Papillomaviridae / Q000235:genetics* / Q000378:metabolism*; D050725:Papillomavirus E7 Proteins; D011485:Protein Binding; D016755:Proto-Oncogene Proteins c-jun / Q000235:genetics / Q000378:metabolism; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D016160:Retinoblastoma Protein / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism; D017384:Sequence Deletion; D018808:Transcription Factor AP-1 / Q000378:metabolism*; D015533:Transcriptional Activation
D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D016755:Proto-Oncogene Proteins c-jun; D011993:Recombinant Fusion Proteins; D016160:Retinoblastoma Protein; D018808:Transcription Factor AP-1; C059731:oncogene protein E7, Human papillomavirus type 16