Human papillomavirus type 16 E7 regulates E2F and contributes to mitogenic signalling.
We have produced human papillomavirus type 16 E7 protein in a bacterial expression system and examined the mitogenic activity of this protein in Swiss 3T3 cells after scrape loading. The ability of E7 to induce cellular DNA synthesis in quiescent mouse fibroblasts is strongly enhanced by the presence of a single growth factor such as insulin. Although only weakly mitogenic, introduction of E7 alone resulted in the rapid induction of the transcriptionally active form of E2F, which was not enhanced further by the addition of insulin. Mutant E7 proteins defective for RB binding failed to induce the active form of E2F or act synergistically with insulin to stimulate DNA synthesis. The ability of E7 to regulate E2F may therefore be necessary, but is not sufficient, for full induction of DNA synthesis.
Morris
J D
JD
Ludwig Institute for Cancer Research, St Mary's Hospital Medical School, London, UK.
Crook
T
T
Bandara
L R
LR
Davies
R
R
LaThangue
N B
NB
Vousden
K H
KH
D016475:3T3 Cells; D000818:Animals; D001483:Base Sequence; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D004261:DNA Replication; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D066298:In Vitro Techniques; D007328:Insulin / Q000494:pharmacology; D051379:Mice; D008938:Mitosis; D008969:Molecular Sequence Data; D009856:Oncogene Proteins, Viral / Q000276:immunology / Q000494:pharmacology*; D050725:Papillomavirus E7 Proteins; D011993:Recombinant Fusion Proteins / Q000494:pharmacology; D011994:Recombinant Proteins; D056465:Retinoblastoma-Binding Protein 1; D050680:Transcription Factor DP1; D014157:Transcription Factors / Q000378:metabolism*
C533431:Arid4a protein, mouse; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D007328:Insulin; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D011993:Recombinant Fusion Proteins; D011994:Recombinant Proteins; D056465:Retinoblastoma-Binding Protein 1; D050680:Transcription Factor DP1; D014157:Transcription Factors; C059731:oncogene protein E7, Human papillomavirus type 16