Skip to main content
Top
Published in: Archives of Virology 1/2009

01-01-2009 | Original Article

HPV16 E6 oncoprotein increases cell adhesion in human keratinocytes

Authors: Alexander Epshtein, A. Jackman, P. Gonen, L. Sherman

Published in: Archives of Virology | Issue 1/2009

Login to get access

Abstract

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.
Literature
1.
go back to reference Alfandari J, Shnitman Magal S, Jackman A, Schlegel R, Gonen P, Sherman L (1999) HPV16 E6 oncoprotein inhibits apoptosis induced during serum-calcium differentiation of foreskin human keratinocytes. Virology 257:383–396PubMedCrossRef Alfandari J, Shnitman Magal S, Jackman A, Schlegel R, Gonen P, Sherman L (1999) HPV16 E6 oncoprotein inhibits apoptosis induced during serum-calcium differentiation of foreskin human keratinocytes. Virology 257:383–396PubMedCrossRef
2.
go back to reference Ben-Ze’ev A (1983) Virus replication in infected epithelial cells is coupled to cell shape-responsive metabolic controls. J Cell Physiol 114:145–152PubMedCrossRef Ben-Ze’ev A (1983) Virus replication in infected epithelial cells is coupled to cell shape-responsive metabolic controls. J Cell Physiol 114:145–152PubMedCrossRef
3.
go back to reference Cooper B, Brimer N, Vande Pol SB (2007) Human papillomavirus E6 regulates the cytoskeleton dynamics of keratinocytes through targeted degradation of p53. J Virol 81:12675–12679PubMedCrossRef Cooper B, Brimer N, Vande Pol SB (2007) Human papillomavirus E6 regulates the cytoskeleton dynamics of keratinocytes through targeted degradation of p53. J Virol 81:12675–12679PubMedCrossRef
4.
go back to reference Crook T, Tidy JA, Vousden KH (1991) Degradation of p53 can be targeted by HPV E6 sequences distinct from those required for p53 binding and transactivation. Cell 67:547–556PubMedCrossRef Crook T, Tidy JA, Vousden KH (1991) Degradation of p53 can be targeted by HPV E6 sequences distinct from those required for p53 binding and transactivation. Cell 67:547–556PubMedCrossRef
5.
go back to reference Doorbar J (2006) Molecular biology of human papillomavirus infection and cervical cancer. Clin Sci 110:525–541PubMedCrossRef Doorbar J (2006) Molecular biology of human papillomavirus infection and cervical cancer. Clin Sci 110:525–541PubMedCrossRef
7.
go back to reference Frisch SM, Francis H (1994) Disruption of epithelial cell-matrix interactions induces apoptosis. J Cell Biol 124:619–626PubMedCrossRef Frisch SM, Francis H (1994) Disruption of epithelial cell-matrix interactions induces apoptosis. J Cell Biol 124:619–626PubMedCrossRef
8.
go back to reference Garnett TO, Duerksen-Hughes PJ (2006) Modulation of apoptosis by human papillomavirus (HPV) oncoproteins. Arch Virol 151:2321–2335PubMedCrossRef Garnett TO, Duerksen-Hughes PJ (2006) Modulation of apoptosis by human papillomavirus (HPV) oncoproteins. Arch Virol 151:2321–2335PubMedCrossRef
9.
go back to reference Gilmore AP, Metcalfe AD, Romer LH, Streuli CH (2000) Integrin-mediated survival signals regulate the apoptotic function of Bax through its conformation and subcellular localization. J Cell Biol 149:431–446PubMedCrossRef Gilmore AP, Metcalfe AD, Romer LH, Streuli CH (2000) Integrin-mediated survival signals regulate the apoptotic function of Bax through its conformation and subcellular localization. J Cell Biol 149:431–446PubMedCrossRef
10.
go back to reference Golubovskaya VM, Finch R, Kweh F, Massoll NA, Campbell-Thompson M, Wallace MR, Cance WG (2008) p53 Regulates FAK Expression in Human Tumor Cells. Mol Carcinog 47:373–382PubMedCrossRef Golubovskaya VM, Finch R, Kweh F, Massoll NA, Campbell-Thompson M, Wallace MR, Cance WG (2008) p53 Regulates FAK Expression in Human Tumor Cells. Mol Carcinog 47:373–382PubMedCrossRef
11.
go back to reference Kim LT, Wu J, Bier-Laning C, Dollar BT, Turnage RH (2000) Focal adhesion kinase up-regulation and signaling in activated keratinocytes. J Surg Res 91:65–69PubMedCrossRef Kim LT, Wu J, Bier-Laning C, Dollar BT, Turnage RH (2000) Focal adhesion kinase up-regulation and signaling in activated keratinocytes. J Surg Res 91:65–69PubMedCrossRef
12.
go back to reference Li B, Dou QP (2000) Bax degradation by the ubiquitin/proteasome-dependent pathway: involvement in tumor survival and progression. Proc Natl Acad Sci USA 97:3850–3855PubMedCrossRef Li B, Dou QP (2000) Bax degradation by the ubiquitin/proteasome-dependent pathway: involvement in tumor survival and progression. Proc Natl Acad Sci USA 97:3850–3855PubMedCrossRef
13.
go back to reference Lim S-T, Chen XL, Lim Y, Hanson DA, Vo T-T, Howerton K, Larocque N, Fisher SJ, Schlaepfer DD, Ilic D (2008) Nuclear FAK promotes cell proliferation and survival through FERM-enhanced p53 degradation. Mol Cell 29:9–22PubMedCrossRef Lim S-T, Chen XL, Lim Y, Hanson DA, Vo T-T, Howerton K, Larocque N, Fisher SJ, Schlaepfer DD, Ilic D (2008) Nuclear FAK promotes cell proliferation and survival through FERM-enhanced p53 degradation. Mol Cell 29:9–22PubMedCrossRef
14.
go back to reference Liu Y, Baleja JD (2008) Structure and function of the papillomavirus E6 protein and its interacting proteins. Front Biosci 13:121–134PubMedCrossRef Liu Y, Baleja JD (2008) Structure and function of the papillomavirus E6 protein and its interacting proteins. Front Biosci 13:121–134PubMedCrossRef
15.
go back to reference Merck manual for diagnosis and therapy. In: Porter RS, Kaplan JL, Homeier BP, Beers M (eds) Merck Research Laboratories, Merck & Co., Inc., Whitehouse Station Merck manual for diagnosis and therapy. In: Porter RS, Kaplan JL, Homeier BP, Beers M (eds) Merck Research Laboratories, Merck & Co., Inc., Whitehouse Station
16.
go back to reference Mitra SK, Schlaepfer DD (2006) Integrin-regulated FAK-Src signaling in normal and cancer cells. Curr Opin Cell Biol 18:516–523PubMedCrossRef Mitra SK, Schlaepfer DD (2006) Integrin-regulated FAK-Src signaling in normal and cancer cells. Curr Opin Cell Biol 18:516–523PubMedCrossRef
17.
go back to reference Nguyen ML, Nguyen MM, Lee D, Griep AE, Lambert PF (2003) The PDZ ligand domain of the human papillomavirus type 16 E6 protein is required for E6’s induction of epithelial hyperplasia in vivo. J Virol 77:6957–6964PubMedCrossRef Nguyen ML, Nguyen MM, Lee D, Griep AE, Lambert PF (2003) The PDZ ligand domain of the human papillomavirus type 16 E6 protein is required for E6’s induction of epithelial hyperplasia in vivo. J Virol 77:6957–6964PubMedCrossRef
18.
go back to reference Oktay MH, Oktay K, Hamele-Bena D, Buyuk A, Koss LG (2003) Focal adhesion kinase as a marker of malignant phenotype in breast and cervical carcinomas. Hum Pathol 34:240–245PubMedCrossRef Oktay MH, Oktay K, Hamele-Bena D, Buyuk A, Koss LG (2003) Focal adhesion kinase as a marker of malignant phenotype in breast and cervical carcinomas. Hum Pathol 34:240–245PubMedCrossRef
19.
go back to reference Playford MP, Schaller MD (2004) The interplay between Src and integrins in normal and tumor biology. Oncogene 23:7928–7946PubMedCrossRef Playford MP, Schaller MD (2004) The interplay between Src and integrins in normal and tumor biology. Oncogene 23:7928–7946PubMedCrossRef
20.
go back to reference Raz A, Ben-Ze’ev A (1982) Growth control and cell spreading: differential response in pre-neoplastic and in metastatic cell variants. Int J Cancer 29:711–715PubMedCrossRef Raz A, Ben-Ze’ev A (1982) Growth control and cell spreading: differential response in pre-neoplastic and in metastatic cell variants. Int J Cancer 29:711–715PubMedCrossRef
21.
go back to reference Rozengurt E, Guha S, Sinnett-Smith S (2002) Gastrointestinal peptide signaling in health and disease. Eur J Surg Suppl 587:23–38PubMed Rozengurt E, Guha S, Sinnett-Smith S (2002) Gastrointestinal peptide signaling in health and disease. Eur J Surg Suppl 587:23–38PubMed
22.
go back to reference Sherman L, Schlegel R (1996) Serum- and calcium-induced differentiation of human keratinocytes is inhibited by the E6 oncoprotein of human papillomavirus type 16. J Virol 70:3269–3279PubMed Sherman L, Schlegel R (1996) Serum- and calcium-induced differentiation of human keratinocytes is inhibited by the E6 oncoprotein of human papillomavirus type 16. J Virol 70:3269–3279PubMed
23.
go back to reference Sherman L, Itzhaki H, Jackman A, Chen JJ, Koval D, Schlegel R (2002) Inhibition of serum- and calcium-induced terminal differentiation of human keratinocytes by HPV 16 E6: Study of the association with p53 degradation, inhibition of p53 transactivation, and binding to E6BP. Virology 292:309–320PubMedCrossRef Sherman L, Itzhaki H, Jackman A, Chen JJ, Koval D, Schlegel R (2002) Inhibition of serum- and calcium-induced terminal differentiation of human keratinocytes by HPV 16 E6: Study of the association with p53 degradation, inhibition of p53 transactivation, and binding to E6BP. Virology 292:309–320PubMedCrossRef
24.
go back to reference Sherman L, Jackman A, Itzhaki H, Stoppler CM, Koval D, Schlegel R (1997) Inhibition of serum- and calcium-induced differentiation of human keratinocytes by HPV16 E6 oncoprotein: role of p53 inactivation. Virology 237:296–306PubMedCrossRef Sherman L, Jackman A, Itzhaki H, Stoppler CM, Koval D, Schlegel R (1997) Inhibition of serum- and calcium-induced differentiation of human keratinocytes by HPV16 E6 oncoprotein: role of p53 inactivation. Virology 237:296–306PubMedCrossRef
25.
go back to reference Shnitman Magal S, Jackman A, Pei X-F, Schlegel R, Sherman L (1998) Induction of apoptosis in human keratinocytes containing mutated p53 alleles and its inhibition by both the E6 and E7 oncoproteins. Int J Cancer 75:96–104CrossRef Shnitman Magal S, Jackman A, Pei X-F, Schlegel R, Sherman L (1998) Induction of apoptosis in human keratinocytes containing mutated p53 alleles and its inhibition by both the E6 and E7 oncoproteins. Int J Cancer 75:96–104CrossRef
26.
go back to reference Stubenrauch F, Laimins LA (1999) Human papillomavirus life cycle: active and latent phases. Semin Cancer Biol 9:379–386PubMedCrossRef Stubenrauch F, Laimins LA (1999) Human papillomavirus life cycle: active and latent phases. Semin Cancer Biol 9:379–386PubMedCrossRef
27.
go back to reference Thomas M, Banks L (1998) Inhibition of bak-induced apoptosis by HPV18 E6. Oncogene 10:2943–2954CrossRef Thomas M, Banks L (1998) Inhibition of bak-induced apoptosis by HPV18 E6. Oncogene 10:2943–2954CrossRef
28.
go back to reference Thomas M, Matlashewski G, Pim D, Banks L (1996) Induction of apoptosis by p53 is independent of its oligomeric state and can be abolished by HPV-18 E6 through ubiquitin mediated degradation. Oncogene 13:265–273PubMed Thomas M, Matlashewski G, Pim D, Banks L (1996) Induction of apoptosis by p53 is independent of its oligomeric state and can be abolished by HPV-18 E6 through ubiquitin mediated degradation. Oncogene 13:265–273PubMed
29.
go back to reference Tong X, Howley PM (1997) The bovine papillomavirus E6 oncoprotein interacts with paxillin and disrupts the actin cytoskeleton. Proc Natl Acad Sci USA 94:4412–4417PubMedCrossRef Tong X, Howley PM (1997) The bovine papillomavirus E6 oncoprotein interacts with paxillin and disrupts the actin cytoskeleton. Proc Natl Acad Sci USA 94:4412–4417PubMedCrossRef
30.
go back to reference Tucker RW, Butterfield CE, Folkman J (1981) Interaction of serum and cell spreading affects the growth of neoplastic and non-neoplastic cells. J Supramol Struct 15:29–40CrossRef Tucker RW, Butterfield CE, Folkman J (1981) Interaction of serum and cell spreading affects the growth of neoplastic and non-neoplastic cells. J Supramol Struct 15:29–40CrossRef
31.
go back to reference Vande Pol SB, Brown MC, Turner CE (1998) Association of bovine papillomavirus type 1 E6 oncoprotein with the focal adhesion protein paxillin through a conserved protein interaction motif. Oncogene 16:43–52CrossRef Vande Pol SB, Brown MC, Turner CE (1998) Association of bovine papillomavirus type 1 E6 oncoprotein with the focal adhesion protein paxillin through a conserved protein interaction motif. Oncogene 16:43–52CrossRef
32.
go back to reference Vande Pol SB, Brown MC, Turner CE (1998) Association of bovine papillomavirus Type 1 E6 oncoprotein with the focal adhesion protein paxillin through a conserved protein interaction motif. Oncogene 16:43–52CrossRef Vande Pol SB, Brown MC, Turner CE (1998) Association of bovine papillomavirus Type 1 E6 oncoprotein with the focal adhesion protein paxillin through a conserved protein interaction motif. Oncogene 16:43–52CrossRef
33.
go back to reference Wade R, Bohl J, Vande Pol S (2002) Paxillin null embryonic stem cells are impaired in cell spreading and tyrosine phosphorylation of focal adhesion kinase. Oncogene 21:96–107PubMedCrossRef Wade R, Bohl J, Vande Pol S (2002) Paxillin null embryonic stem cells are impaired in cell spreading and tyrosine phosphorylation of focal adhesion kinase. Oncogene 21:96–107PubMedCrossRef
34.
go back to reference Zheng ZM, Baker CC (2006) Papillomavirus genome structure, expression, post-translational regulation. Front Biosci 11:2286–2302PubMedCrossRef Zheng ZM, Baker CC (2006) Papillomavirus genome structure, expression, post-translational regulation. Front Biosci 11:2286–2302PubMedCrossRef
35.
go back to reference Zur Hausen H (1996) Papillomavirus infections—a major cause of human cancers. Biochim Biophys Acta 1288:F55–F78PubMed Zur Hausen H (1996) Papillomavirus infections—a major cause of human cancers. Biochim Biophys Acta 1288:F55–F78PubMed
Metadata
Title
HPV16 E6 oncoprotein increases cell adhesion in human keratinocytes
Authors
Alexander Epshtein
A. Jackman
P. Gonen
L. Sherman
Publication date
01-01-2009
Publisher
Springer Vienna
Published in
Archives of Virology / Issue 1/2009
Print ISSN: 0304-8608
Electronic ISSN: 1432-8798
DOI
https://doi.org/10.1007/s00705-008-0273-9

Other articles of this Issue 1/2009

Archives of Virology 1/2009 Go to the issue

Virology Division News

The order Herpesvirales

Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.