HPV type 16 E6 and NFX1-123 augment JNK signaling to mediate keratinocyte differentiation and L1 expression.

HPV type 16 E6 and NFX1-123 augment JNK signaling to mediate keratinocyte differentiation and L1 expression.
Virology. 2019 Mar 16;531:171-182
Authors: Levan J, Vliet-Gregg PA, Robinson KL, Matsumoto LR, Katzenellenbogen RA
Abstract
The HPV life cycle is differentiation-dependent, with cellular differentiation driving initiation of the late, productive stage of the viral life cycle. Here, we identify a role for the protein NFX1-123 in regulating keratinocyte differentiation and events of the late HPV life cycle. NFX1-123 itself increased with differentiation of epithelial cells. Greater NFX1-123 augmented differentiation marker expression and JNK phosphorylation in differentiating 16E6-expressing human foreskin keratinocytes (16E6 HFKs). This was associated with altered expression of MKK4 and MKK7, upstream kinase regulators of JNK phosphorylation. Modulating levels of NFX1-123 in HPV16-positive W12E cells recapitulated the effects on differentiation markers, JNK phosphorylation, and MKK4/7 seen in 16E6 HFKs. Crucially, levels of NFX1-123 also correlated with expression of L1, the capsid protein of HPV. Altogether, these studies define a role for NFX1-123 in mediating epithelial differentiation through the JNK signaling pathway, potentially linking expression of cellular genes and HPV genes during differentiation.
PMID: 30903928 [PubMed - as supplied by publisher]

Source: Virology - March 15, 2019 Category: Virology Authors: Levan J, Vliet-Gregg PA, Robinson KL, Matsumoto LR, Katzenellenbogen RA Tags: Virology Source Type: research