HPV16 E6 oncoprotein increases cell adhesion in human keratinocytes.
Expression of the E6 oncoprotein of human papillomavirus (HPV) 16 in primary human keratinocytes (PHKs) was previously shown to significantly reduce apoptosis. This could be due to increased cell adhesion. Adhesion ability was tested by seeding cells on tissue culture dishes coated with different concentrations of poly(HEME) and determination of the proportion of attached cells. Assays were carried out with PHKs, immortalized human keratinocytes (HaCaT) and human 293T cells. The E6 gene was transduced via retroviral infection or DNA transfection. Results of these assays showed that expression of E6 increased the proportion of cells that attached to poly(HEME). Several HPV16 E6 mutants were also tested in the above assay in 293T cells. These assays showed that the p53 targeting region of E6 is dispensable for this activity. Assays of inhibition of tyrosine kinases by bombesin showed that E6 probably utilizes other pathways to increase cell adhesion.
Epshtein
Alexander
A
Department of Human Microbiology, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel. epshtein@sbcglobal.net
Jackman
A
A
Gonen
P
P
Sherman
L
L
D000595:Amino Acid Sequence; D017209:Apoptosis / Q000187:drug effects; D016227:Benzoquinones / Q000494:pharmacology; D001839:Bombesin / Q000494:pharmacology; D002448:Cell Adhesion / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D002460:Cell Line; D004791:Enzyme Inhibitors / Q000494:pharmacology; D051417:Focal Adhesion Kinase 1 / Q000378:metabolism; D005786:Gene Expression Regulation; D006454:Hemoglobins / Q000378:metabolism; D052162:Human papillomavirus 16 / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D015603:Keratinocytes / Q000378:metabolism* / Q000821:virology; D047029:Lactams, Macrocyclic / Q000494:pharmacology; D008969:Molecular Sequence Data; D009154:Mutation; D018377:Neurotransmitter Agents / Q000494:pharmacology; D009856:Oncogene Proteins, Viral / Q000235:genetics / Q000378:metabolism*; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D017828:Rifabutin / Q000031:analogs & derivatives; D016415:Sequence Alignment; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
D016227:Benzoquinones; C068651:E6 protein, Human papillomavirus type 16; D004791:Enzyme Inhibitors; D006454:Hemoglobins; D047029:Lactams, Macrocyclic; D018377:Neurotransmitter Agents; D009856:Oncogene Proteins, Viral; C509893:PolyHeme; D012097:Repressor Proteins; D016159:Tumor Suppressor Protein p53; D017828:Rifabutin; C020754:herbimycin; D051417:Focal Adhesion Kinase 1; C496050:PTK2 protein, human; D001839:Bombesin