title: NF-κB signalling is attenuated by the E7 protein from cutaneous human papillomaviruses.
abstract: The high-risk Alpha-types of human papillomavirus (HPV) are the causative agent of cervical cancer, which is the second major cause of death among women worldwide. Recent investigations have shown that E7 from the Alpha-papillomavirus HPV-16 interacts with IKKα and IKKβ of the IKK complex in the NF-κB pathway leading to an attenuation of the activity. There is a possible link between development of non-melanoma skin cancer and cutaneous Beta-papillomavirus but if these HPV types attenuate the NF-κB pathway is unclear. Seven different E7 proteins, representing four out of the five different species of the Beta genus (HPV-20, -37, -38, -92, -93 and -96) and one from the Gamma genus (HPV-4) were investigated for potential modulation of the NF-κB pathway in U2OS cells. Our results demonstrate that E7 from all the cutaneous HPV types were capable of inhibiting the NF-κB activity as well as E7 from HPV-16. In addition, E7 proteins from the cutaneous HPV types demonstrated interaction with IKKα but not with IKKβ. The deregulation of the NF-κB pathway by cutaneous HPVs might contribute to the pathogenesis of non-melanoma skin cancers and its precursors.
authors: The DNA Tumour Virus Group, Department of Cellular and Molecular Medicine, University of Copenhagen, Denmark.
authors: Luise M
authors: LM
authors: Byg
authors: Jessica
authors: J
authors: Vidlund
authors: Natasa
authors: N
authors: Vasiljevic
authors: Dorte
authors: D
authors: Clausen
authors: Ola
authors: O
authors: Forslund
authors: Bodil
authors: B
authors: Norrild
mesh_terms: D052686:Betapapillomavirus / Q000276:immunology / Q000472:pathogenicity*; D002460:Cell Line; D052689:Gammapapillomavirus / Q000276:immunology / Q000472:pathogenicity*; D006801:Humans; D051550:I-kappa B Kinase / Q000037:antagonists & inhibitors*; D007108:Immune Tolerance; D016328:NF-kappa B / Q000037:antagonists & inhibitors; D050725:Papillomavirus E7 Proteins / Q000276:immunology / Q000378:metabolism*; D025941:Protein Interaction Mapping; D015398:Signal Transduction; D012878:Skin Neoplasms / Q000821:virology
chemical_list: D016328:NF-kappa B; D050725:Papillomavirus E7 Proteins; D051550:I-kappa B Kinase