title: Disc large 1 expression is altered by human papillomavirus E6/E7 proteins in organotypic cultures of human keratinocytes.
abstract: Loss of cell polarity is a fundamental process in cell transformation. Among polarity proteins, we focused on human disc large (DLG1), which is localized mainly at adherens junctions and contributes to the control of cell proliferation. We previously demonstrated that its expression is altered in HPV-associated cervical neoplastic lesions, but the mechanisms beyond this remain unknown. In this study, we analysed the contribution of HPV proteins to the changes in DLG1 expression in the squamous epithelium. We observed tissue and intracellular misdistribution of DLG1 when high-risk HPV-18 E7 or E6/E7 proteins were expressed in organotypic raft cultures. The viral oncoproteins induce the loss of DLG1 from the cell borders and an increase in the level of DLG1 protein, reflecting the pattern observed in cervical lesions. These findings were corroborated in cultures bearing the entire HPV-18 genome. Interestingly, changes in tissue distribution and abundance of DLG1 were also detected in organotypic cultures expressing the low-risk HPV-11 E7 or E6/E7 proteins, suggesting a conserved function among different HPV types. However, for low-risk HPVs, the subcellular localization of DLG1 at cell-to-cell contacts was predominantly maintained. This report offers new evidence, we believe, of the involvement of HPV proteins in DLG1 expression pattern and our data support previous observations regarding DLG1 expression in cervical lesions.
authors.affiliation: Instituto de Biología Molecular y Celular de Rosario - CONICET, Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario, Suipacha 531, Rosario, Argentina.
authors.forename: M Bugnon
authors.initials: MB
authors.lastname: Valdano
authors.affiliation: Instituto de Biología Molecular y Celular de Rosario - CONICET, Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario, Suipacha 531, Rosario, Argentina.
authors.forename: A L
authors.initials: AL
authors.lastname: Cavatorta
authors.affiliation: Deparment of Biochemistry, Institute of Chemistry, University of Sao Paulo, Sao Paulo, Brazil.
authors.forename: M G
authors.initials: MG
authors.lastname: Morale
authors.affiliation: Instituto de Biología Molecular y Celular de Rosario - CONICET, Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario, Suipacha 531, Rosario, Argentina.
authors.forename: F
authors.initials: F
authors.lastname: Marziali
authors.affiliation: Department of Microbiology, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, Brazil.
authors.forename: V
authors.initials: V
authors.lastname: de Souza Lino
authors.affiliation: Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: R D M
authors.initials: RDM
authors.lastname: Steenbergen
authors.affiliation: Department of Microbiology, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, Brazil.
authors.forename: E
authors.initials: E
authors.lastname: Boccardo
authors.affiliation: Instituto de Biología Molecular y Celular de Rosario - CONICET, Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario, Suipacha 531, Rosario, Argentina.
authors.forename: D
authors.initials: D
authors.lastname: Gardiol
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000378:metabolism*; D000074288:Discs Large Homolog 1 Protein; D054884:Host-Pathogen Interactions; D052161:Human papillomavirus 18 / Q000254:growth & development*; D006801:Humans; D015603:Keratinocytes / Q000821:virology*; D008565:Membrane Proteins / Q000378:metabolism*; D009856:Oncogene Proteins, Viral / Q000378:metabolism*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C513314:DLG1 protein, human; D004268:DNA-Binding Proteins; D000074288:Discs Large Homolog 1 Protein; C469553:E6 protein, Human papillomavirus type 11; C052603:E6 protein, Human papillomavirus type 18; C052633:E7 protein, Human papillomavirus type 18; C493190:E7 protein, human papillomavirus 11; D008565:Membrane Proteins; D009856:Oncogene Proteins, Viral