Abstract
Cutaneous β-human papillomavirus (β-HPV) E6 proteins inhibit NOTCH signaling by associating with the transcriptional coactivator MAML1. NOTCH has tumor suppressor activities in epithelial cells and is activated during keratinocyte differentiation. Here we report that HPV type 8 (HPV8) E6 subverts NOTCH activation during keratinocyte differentiation by inhibiting RBPJ/MAML1 transcriptional activator complexes at NOTCH target DNA. NOTCH inhibition impairs epithelial differentiation and may thus contribute to β-HPV replication and viral oncogenesis.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Cell Differentiation*
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Cells, Cultured
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DNA-Binding Proteins / metabolism*
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Humans
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Immunoglobulin J Recombination Signal Sequence-Binding Protein / metabolism*
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Keratinocytes / physiology
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Keratinocytes / virology*
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Oncogene Proteins, Viral / metabolism*
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Papillomaviridae / pathogenicity*
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Receptors, Notch / antagonists & inhibitors*
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Transcription Factors / metabolism*
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Virulence Factors / metabolism
Substances
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DNA-Binding Proteins
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E6 protein, Human papillomavirus type 8
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Immunoglobulin J Recombination Signal Sequence-Binding Protein
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MAML1 protein, human
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Oncogene Proteins, Viral
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RBPJ protein, human
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Receptors, Notch
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Transcription Factors
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Virulence Factors