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Title: Human papillomavirus 16E6 and NFX1-123 potentiate notch signaling and differentiation without activating cellular arrest

Abstract

High-risk human papillomavirus (HR HPV) oncoproteins bind host cell proteins to dysregulate and uncouple apoptosis, senescence, differentiation, and growth. These pathways are important for both the viral life cycle and cancer development. HR HPV16 E6 (16E6) interacts with the cellular protein NFX1-123, and they collaboratively increase the growth and differentiation master regulator, Notch1. In 16E6 expressing keratinocytes (16E6 HFKs), the Notch canonical pathway genes Hes1 and Hes5 were increased with overexpression of NFX1-123, and their expression was directly linked to the activation or blockade of the Notch1 receptor. Keratinocyte differentiation genes Keratin 1 and Keratin 10 were also increased, but in contrast their upregulation was only indirectly associated with Notch1 receptor stimulation and was fully unlinked to growth arrest, increased p21{sup Waf1/CIP1}, or decreased proliferative factor Ki67. This leads to a model of 16E6, NFX1-123, and Notch1 differently regulating canonical and differentiation pathways and entirely uncoupling cellular arrest from increased differentiation. - Highlights: • 16E6 and NFX1-123 increased the Notch canonical pathway through Notch1. • 16E6 and NFX1-123 increased the differentiation pathway indirectly through Notch1. • 16E6 and NFX1-123 increased differentiation gene expression without growth arrest. • Increased NFX1-123 with 16E6 may create an ideal cellular phenotype for HPV.

Authors:
;  [1]
  1. Center for Global Infectious Disease Research, Seattle Children's Research Institute, 1900 Ninth Ave., Seattle, WA 98101 (United States)
Publication Date:
OSTI Identifier:
22470160
Resource Type:
Journal Article
Journal Name:
Virology
Additional Journal Information:
Journal Volume: 478; Other Information: Copyright (c) 2015 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0042-6822
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; APOPTOSIS; CELL CYCLE; GENES; HAZARDS; HUMAN POPULATIONS; KERATIN; LIFE CYCLE; NEOPLASMS; PHENOTYPE; PLANT GROWTH; RECEPTORS; SIGNALS; STIMULATION

Citation Formats

Vliet-Gregg, Portia A., Hamilton, Jennifer R., Katzenellenbogen, Rachel A., E-mail: rkatzen@uw.edu, and Department of Pediatrics, Division of Adolescent Medicine, University of Washington, Seattle WA. Human papillomavirus 16E6 and NFX1-123 potentiate notch signaling and differentiation without activating cellular arrest. United States: N. p., 2015. Web. doi:10.1016/J.VIROL.2015.02.002.
Vliet-Gregg, Portia A., Hamilton, Jennifer R., Katzenellenbogen, Rachel A., E-mail: rkatzen@uw.edu, & Department of Pediatrics, Division of Adolescent Medicine, University of Washington, Seattle WA. Human papillomavirus 16E6 and NFX1-123 potentiate notch signaling and differentiation without activating cellular arrest. United States. https://doi.org/10.1016/J.VIROL.2015.02.002
Vliet-Gregg, Portia A., Hamilton, Jennifer R., Katzenellenbogen, Rachel A., E-mail: rkatzen@uw.edu, and Department of Pediatrics, Division of Adolescent Medicine, University of Washington, Seattle WA. 2015. "Human papillomavirus 16E6 and NFX1-123 potentiate notch signaling and differentiation without activating cellular arrest". United States. https://doi.org/10.1016/J.VIROL.2015.02.002.
@article{osti_22470160,
title = {Human papillomavirus 16E6 and NFX1-123 potentiate notch signaling and differentiation without activating cellular arrest},
author = {Vliet-Gregg, Portia A. and Hamilton, Jennifer R. and Katzenellenbogen, Rachel A., E-mail: rkatzen@uw.edu and Department of Pediatrics, Division of Adolescent Medicine, University of Washington, Seattle WA},
abstractNote = {High-risk human papillomavirus (HR HPV) oncoproteins bind host cell proteins to dysregulate and uncouple apoptosis, senescence, differentiation, and growth. These pathways are important for both the viral life cycle and cancer development. HR HPV16 E6 (16E6) interacts with the cellular protein NFX1-123, and they collaboratively increase the growth and differentiation master regulator, Notch1. In 16E6 expressing keratinocytes (16E6 HFKs), the Notch canonical pathway genes Hes1 and Hes5 were increased with overexpression of NFX1-123, and their expression was directly linked to the activation or blockade of the Notch1 receptor. Keratinocyte differentiation genes Keratin 1 and Keratin 10 were also increased, but in contrast their upregulation was only indirectly associated with Notch1 receptor stimulation and was fully unlinked to growth arrest, increased p21{sup Waf1/CIP1}, or decreased proliferative factor Ki67. This leads to a model of 16E6, NFX1-123, and Notch1 differently regulating canonical and differentiation pathways and entirely uncoupling cellular arrest from increased differentiation. - Highlights: • 16E6 and NFX1-123 increased the Notch canonical pathway through Notch1. • 16E6 and NFX1-123 increased the differentiation pathway indirectly through Notch1. • 16E6 and NFX1-123 increased differentiation gene expression without growth arrest. • Increased NFX1-123 with 16E6 may create an ideal cellular phenotype for HPV.},
doi = {10.1016/J.VIROL.2015.02.002},
url = {https://www.osti.gov/biblio/22470160}, journal = {Virology},
issn = {0042-6822},
number = ,
volume = 478,
place = {United States},
year = {Wed Apr 15 00:00:00 EDT 2015},
month = {Wed Apr 15 00:00:00 EDT 2015}
}