The human papillomavirus type 8 E6 protein interferes with NOTCH activation during keratinocyte differentiation.
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.
Division of Infectious Disease, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Jordan M
JM
Meyers
Jennifer M
JM
Spangle
Karl
K
Munger
D002454:Cell Differentiation; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000378:metabolism*; D006801:Humans; D051819:Immunoglobulin J Recombination Signal Sequence-Binding Protein / Q000378:metabolism*; D015603:Keratinocytes / Q000502:physiology / Q000821:virology*; D009856:Oncogene Proteins, Viral / Q000378:metabolism*; D027383:Papillomaviridae / Q000472:pathogenicity*; D051880:Receptors, Notch / Q000037:antagonists & inhibitors*; D014157:Transcription Factors / Q000378:metabolism*; D037521:Virulence Factors / Q000378:metabolism
D004268:DNA-Binding Proteins; C466081:E6 protein, Human papillomavirus type 8; D051819:Immunoglobulin J Recombination Signal Sequence-Binding Protein; C430872:MAML1 protein, human; D009856:Oncogene Proteins, Viral; C497570:RBPJ protein, human; D051880:Receptors, Notch; D014157:Transcription Factors; D037521:Virulence Factors