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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Sequence
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Animals
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Base Sequence
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Cell Transformation, Neoplastic / genetics
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Cell Transformation, Neoplastic / metabolism
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Cells, Cultured
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / metabolism*
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DNA-Binding Proteins / physiology*
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Gene Expression Regulation, Enzymologic
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Humans
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MAP Kinase Kinase 1 / metabolism
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MAP Kinase Kinase 1 / physiology
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Matrix Metalloproteinase 9 / genetics*
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Matrix Metalloproteinase 9 / metabolism
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Mice
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Mitogen-Activated Protein Kinase 3 / metabolism
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Molecular Sequence Data
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NIH 3T3 Cells
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Oncogene Proteins, Viral / genetics
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Oncogene Proteins, Viral / metabolism*
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Oncogene Proteins, Viral / physiology*
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Signal Transduction / physiology
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Tissue Distribution
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Transcription Factor AP-1 / metabolism
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Transcription Factor AP-1 / physiology
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Transfection
Substances
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DNA-Binding Proteins
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E2 protein, Human papillomavirus type 16
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Oncogene Proteins, Viral
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Transcription Factor AP-1
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Mitogen-Activated Protein Kinase 3
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MAP Kinase Kinase 1
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Matrix Metalloproteinase 9