Next Article in Journal
Preface of the Special Issue: “Recent CMV Research”
Previous Article in Journal
Evidence of Epstein-Barr Virus Association with Gastric Cancer and Non-Atrophic Gastritis
Article Menu

Export Article

Open AccessArticle
Viruses 2014, 6(1), 319-335; doi:10.3390/v6010319

Brd4-Mediated Nuclear Retention of the Papillomavirus E2 Protein Contributes to Its Stabilization in Host Cells

Department of Microbiology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
Current address: Department of Basic Medicine, Xiamen University School of Medicine, Xiamen, Fujian 361102, China
*
Author to whom correspondence should be addressed.
Received: 2 December 2013 / Revised: 4 January 2014 / Accepted: 9 January 2014 / Published: 20 January 2014
View Full-Text   |   Download PDF [2476 KB, uploaded 12 May 2015]   |  

Abstract

Papillomavirus E2 is a multifunctional viral protein that regulates many aspects of the viral life cycle including viral episome maintenance, transcriptional activation, and repression. E2 is degraded by the ubiquitin-proteasome pathway. Cellular bromodomain protein Brd4 has been implicated in the stabilization of the E2 protein. E2 normally shuttles between the cytoplasm and the nucleus. In this study, we demonstrate that E2 ubiquitylation mostly occurs in the cytoplasm. We also find that the interaction with Brd4 promotes nuclear retention of papillomavirus E2 proteins and contributes to their stabilization in the nucleus. Compared to wild type E2 proteins, nuclear-localization-defective mutants are rapidly degraded by the ubiquitin-proteasome pathway; however, co-expression of Brd4 redirects these mutants into the nucleus and significantly increases their stability. We further demonstrate that tethering E2 proteins to chromatin as either double-bromodomain fusion proteins or histone 2B (H2B) fusion proteins significantly stabilizes the E2 proteins. Our studies suggest that chromatin recruitment of the E2 protein via interaction with Brd4 prevents E2 ubiquitylation and proteasomal degradation in the cytoplasm, leading to its stabilization in the nucleus. These studies bring new insights for understanding Brd4-mediated E2 stabilization, and provide an additional mechanism by which the chromatin-associated Brd4 regulates E2 functions. View Full-Text
Keywords: papillomavirus; E2; Brd4; stability papillomavirus; E2; Brd4; stability
This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).

Supplementary material

Scifeed alert for new publications

Never miss any articles matching your research from any publisher
  • Get alerts for new papers matching your research
  • Find out the new papers from selected authors
  • Updated daily for 49'000+ journals and 6000+ publishers
  • Define your Scifeed now

SciFeed Share & Cite This Article

MDPI and ACS Style

Li, J.; Li, Q.; Diaz, J.; You, J. Brd4-Mediated Nuclear Retention of the Papillomavirus E2 Protein Contributes to Its Stabilization in Host Cells. Viruses 2014, 6, 319-335.

Show more citation formats Show less citations formats

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Viruses EISSN 1999-4915 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top