title: Keratinocyte sensitization to tumour necrosis factor-induced nuclear factor kappa B activation by the E2 regulatory protein of human papillomaviruses.
abstract: Human papillomavirus (HPV) life cycle requires extensive manipulation of cell signalling to provide conditions adequate for viral replication within the stratified epithelia. In this regard, we show that the E2 regulatory protein of α, β and μ-HPV genotypes enhances tumour necrosis factor (TNF)-induced activation of nuclear factor kappa B (NF-κB). This activation is mediated by the N-terminal domain of E2, but does not rely on its transcriptional properties. It is independent of the NF-κB regulator Tax1BP1, which nevertheless interacts with all the E2 proteins. E2 specifically activates NF-κB pathways induced by TNF, while interleukin-1-induced pathways are not affected. E2 stimulates the activating K63-linked ubiquitination of TRAF5, and interacts with both TRAF5 and TRAF6. Our data suggest that E2 potentiates TNF-induced NF-κB signalling mediated by TRAF5 activation through direct binding. Since NF-κB controls epithelial differentiation, this activity may be involved in the commitment of infected keratinocytes to proliferation arrest and differentiation, both required for the implementation of the productive viral cycle.
authors.affiliation: Genetics, Papillomavirus and Human Cancer Unit, Institut Pasteur, 25 rue du Dr Roux, 75724 Paris cedex 15, France.|Human Papillomavirus Unit, Institut Pasteur, Tunis, Tunisia.
authors.forename: Manel
authors.initials: M
authors.lastname: Boulabiar
authors.affiliation: Human Papillomavirus Unit, Institut Pasteur, Tunis, Tunisia.
authors.forename: Samir
authors.initials: S
authors.lastname: Boubaker
authors.affiliation: Genetics, Papillomavirus and Human Cancer Unit, Institut Pasteur, 25 rue du Dr Roux, 75724 Paris cedex 15, France.
authors.forename: Michel
authors.initials: M
authors.lastname: Favre
authors.affiliation: Genetics, Papillomavirus and Human Cancer Unit, Institut Pasteur, 25 rue du Dr Roux, 75724 Paris cedex 15, France.
authors.forename: Caroline
authors.initials: C
authors.lastname: Demeret
mesh_terms: D002460:Cell Line; D006801:Humans; D015603:Keratinocytes / Q000276:immunology* / Q000821:virology*; D016328:NF-kappa B / Q000378:metabolism*; D009856:Oncogene Proteins, Viral / Q000276:immunology*; D011485:Protein Binding
chemical_list: D016328:NF-kappa B; D009856:Oncogene Proteins, Viral