Levan, JustineVliet-Gregg, Portia A.Robinson, Kristin L.Matsumoto, Lisa R.Katzenellenbogen, Rachel A.2020-07-222020-07-222019-03-16Levan, J., Vliet-Gregg, P. A., Robinson, K. L., Matsumoto, L. R., & Katzenellenbogen, R. A. (2019). HPV type 16 E6 and NFX1-123 augment JNK signaling to mediate keratinocyte differentiation and L1 expression. Virology, 531, 171–182. https://doi.org/10.1016/j.virol.2019.03.008https://hdl.handle.net/1805/23316The 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.en-USPublisher PolicyNFX1-123HR HPVHR E6DifferentiationKeratinocyteArticle