title: Influence of HPV16 E2 and its localisation on the expression of matrix metalloproteinase-9.
abstract: Infection with the high-risk HPV types 16 and 18 is the major cause of cervical cancer and plays a role in the development of certain head and neck and skin cancers. We have previously demonstrated that the Early Protein 2 of the Cottontail Rabbit papillomavirus (CRPV), required for skin carcinogenesis in a rabbit model, is able to induce the expression of a matrix metalloproteinase (MMP-9); a protease known to play a key role in invasion and metastasis. However, as of now we do not understand the underlying mechanism of activation nor relevance for the human system. Here, we report that high-risk human papillomavirus HPV16 E2 similar to our previously reported results on CRPV E2 activates the human MMP-9 promoter predominantly via the MEK1-ERK1/2-AP-1-signaling pathway. In addition this activation is associated with a nuclear sub-localisation of HPV16-E2 suggesting a nuclear protein-protein or protein-DNA interaction of E2 as the underlying mechanism of activation.
authors.affiliation: Department of Otolaryngology, University Hospital Heidelberg, 69120 Heidelberg, Germany.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Mühlen
authors.forename: Andreas
authors.initials: A
authors.lastname: Behren
authors.forename: Thomas
authors.initials: T
authors.lastname: Iftner
authors.forename: Christian
authors.initials: C
authors.lastname: Simon
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology*; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D048369:MAP Kinase Kinase 1 / Q000378:metabolism / Q000502:physiology; D020780:Matrix Metalloproteinase 9 / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D008969:Molecular Sequence Data; D041681:NIH 3T3 Cells; D009856:Oncogene Proteins, Viral / Q000235:genetics / Q000378:metabolism* / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology; D014018:Tissue Distribution; D018808:Transcription Factor AP-1 / Q000378:metabolism / Q000502:physiology; D014162:Transfection
chemical_list: D004268:DNA-Binding Proteins; C054855:E2 protein, Human papillomavirus type 16; D009856:Oncogene Proteins, Viral; D018808:Transcription Factor AP-1; D048052:Mitogen-Activated Protein Kinase 3; D048369:MAP Kinase Kinase 1; D020780:Matrix Metalloproteinase 9