Regions of human papillomavirus type 16 E7 oncoprotein required for immortalization of human keratinocytes.
Binding of the retinoblastoma gene product (pRB) by viral oncoproteins, including the E7 of human papillomavirus type 16 (HPV 16), is thought to be important in transformation of cells. One of the steps in transformation is the immortalization process. Here we show that mutations in E7 within the full-length genome which inhibit binding of pRB do not abrogate the ability of the HPV 16 DNA to immortalize primary human epithelial (keratinocyte) cells. A mutation in one of the cysteines of a Cys-X-X-Cys motif which is contained in the carboxy half of the E7 and is part of a zinc finger arrangement completely eliminates the ability of HPV 16 DNA to immortalize cells. The results indicate the importance of E7 in the immortalization of primary keratinocytes but suggest that the binding of pRB is not essential.
Jewers
R J
RJ
Richard Dimbleby Laboratory for Cancer Virology, UMDS, St. Thomas' Hospital, London, England.
Hildebrandt
P
P
Ludlow
J W
JW
Kell
B
B
McCance
D J
DJ
D000595:Amino Acid Sequence; D000818:Animals; D002472:Cell Transformation, Viral; D004252:DNA Mutational Analysis; D006801:Humans; D015603:Keratinocytes / Q000382:microbiology*; D008969:Molecular Sequence Data; D009856:Oncogene Proteins, Viral / Q000737:chemistry* / Q000378:metabolism; D027383:Papillomaviridae / Q000472:pathogenicity*; D050725:Papillomavirus E7 Proteins; D011485:Protein Binding; D016160:Retinoblastoma Protein / Q000378:metabolism; D013329:Structure-Activity Relationship; D016335:Zinc Fingers
D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D016160:Retinoblastoma Protein; C059731:oncogene protein E7, Human papillomavirus type 16