Identifying and Characterizing Interplay between Hepatitis B Virus X Protein and Smc5/6

Hepatitis B X protein (HBx) plays an essential role in the hepatitis B virus (HBV) replication cycle, but the function of HBx has been elusive until recently. It was recently shown that transcription from the HBV genome (covalently-closed circular DNA, cccDNA) is inhibited by the structural maintena...

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Autores principales: Livingston, Christine M., Ramakrishnan, Dhivya, Strubin, Michel, Fletcher, Simon P., Beran, Rudolf K.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2017
Materias:
Review
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5408675/
https://www.ncbi.nlm.nih.gov/pubmed/28368357
http://dx.doi.org/10.3390/v9040069
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author Livingston, Christine M.
Ramakrishnan, Dhivya
Strubin, Michel
Fletcher, Simon P.
Beran, Rudolf K.
author_facet Livingston, Christine M.
Ramakrishnan, Dhivya
Strubin, Michel
Fletcher, Simon P.
Beran, Rudolf K.
author_sort Livingston, Christine M.
collection PubMed
description Hepatitis B X protein (HBx) plays an essential role in the hepatitis B virus (HBV) replication cycle, but the function of HBx has been elusive until recently. It was recently shown that transcription from the HBV genome (covalently-closed circular DNA, cccDNA) is inhibited by the structural maintenance of chromosome 5/6 complex (Smc5/6), and that a key function of HBx is to redirect the DNA-damage binding protein 1 (DDB1) E3 ubiquitin ligase to target this complex for degradation. By doing so, HBx alleviates transcriptional repression by Smc5/6 and stimulates HBV gene expression. In this review, we discuss in detail how the interplay between HBx and Smc5/6 was identified and characterized. We also discuss what is known regarding the repression of cccDNA transcription by Smc5/6, the timing of HBx expression, and the potential role of HBx in promoting hepatocellular carcinoma (HCC).
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spelling pubmed-54086752017-05-18 Identifying and Characterizing Interplay between Hepatitis B Virus X Protein and Smc5/6 Livingston, Christine M. Ramakrishnan, Dhivya Strubin, Michel Fletcher, Simon P. Beran, Rudolf K. Viruses Review Hepatitis B X protein (HBx) plays an essential role in the hepatitis B virus (HBV) replication cycle, but the function of HBx has been elusive until recently. It was recently shown that transcription from the HBV genome (covalently-closed circular DNA, cccDNA) is inhibited by the structural maintenance of chromosome 5/6 complex (Smc5/6), and that a key function of HBx is to redirect the DNA-damage binding protein 1 (DDB1) E3 ubiquitin ligase to target this complex for degradation. By doing so, HBx alleviates transcriptional repression by Smc5/6 and stimulates HBV gene expression. In this review, we discuss in detail how the interplay between HBx and Smc5/6 was identified and characterized. We also discuss what is known regarding the repression of cccDNA transcription by Smc5/6, the timing of HBx expression, and the potential role of HBx in promoting hepatocellular carcinoma (HCC). MDPI 2017-04-03 /pmc/articles/PMC5408675/ /pubmed/28368357 http://dx.doi.org/10.3390/v9040069 Text en © 2017 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Livingston, Christine M.
Ramakrishnan, Dhivya
Strubin, Michel
Fletcher, Simon P.
Beran, Rudolf K.
Identifying and Characterizing Interplay between Hepatitis B Virus X Protein and Smc5/6
title Identifying and Characterizing Interplay between Hepatitis B Virus X Protein and Smc5/6
title_full Identifying and Characterizing Interplay between Hepatitis B Virus X Protein and Smc5/6
title_fullStr Identifying and Characterizing Interplay between Hepatitis B Virus X Protein and Smc5/6
title_full_unstemmed Identifying and Characterizing Interplay between Hepatitis B Virus X Protein and Smc5/6
title_short Identifying and Characterizing Interplay between Hepatitis B Virus X Protein and Smc5/6
title_sort identifying and characterizing interplay between hepatitis b virus x protein and smc5/6
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5408675/
https://www.ncbi.nlm.nih.gov/pubmed/28368357
http://dx.doi.org/10.3390/v9040069
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