Evidence map›Paper›PMID 27626656›Full record

ArticleCell reports2016

Hepatitis B Virus X Protein Promotes Degradation of SMC5/6 to Enhance HBV Replication.

Christopher M Murphy, Yanping Xu, Feng Li, Kouki Nio, Natalia Reszka-Blanco, Xiaodong Li, Yaxu Wu, Yanbao Yu, Yue Xiong, Lishan Su

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 203 papers.

0numbers the graph read from it
0cells of the map it votes in
203citing papers in PubMed
18.4field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

203 citing papers in PubMed, 306 citations in OpenAlex.

  1. Identification ofFrontiers in immunology · 2018
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  19. Structural basis for Lamassu-based antiviral immunity and its evolution from DNA repair machinery.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  20. Article

143 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors at 2 institutions in 1 country.

Christopher M MurphyLineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Yanping XuLineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Department of Biochemistry and Biophysics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Feng LiLineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Kouki NioLineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Natalia Reszka-BlancoLineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Xiaodong LiLineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Yaxu WuLineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Yanbao YuJ. Craig Venter Institute, 9714 Medical Center Drive, Rockville, MD 20850, USA.
Yue XiongLineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Department of Biochemistry and Biophysics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA. Electronic address: yxiong@email.unc.edu.
Lishan SuLineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA. Electronic address: lsu@med.unc.edu.
University of North Carolina at Chapel Hill · USJ. Craig Venter Institute · US

Funding

Virology Research Program (Program 4)P30CA016086 · NCI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI David Darr · 1985 to 2026
$201.5M
The ROC-Cullin Family of E3 Ubiquitin LigasesR01GM067113 · NIGMS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI XIONG, YUE · 2003 to 2019
$5.4M
HIV co-infection and HCV-induced liver fibrosis in vivoR01AI095097 · NIAID · UNIV OF NORTH CAROLINA CHAPEL HILL · PI SU, LISHAN · 2012 to 2016
$1.8M
Treg in HIV-1 Replication and PathogenesisR01AI077454 · NIAID · UNIV OF NORTH CAROLINA CHAPEL HILL · PI SU, LISHAN · 2008 to 2011
$1.5M
NCI NIH HHS P30 CA016086NIAID NIH HHS R01 AI077454NIAID NIH HHS R01 AI095097NIGMS NIH HHS R01 GM067113
6 · The paper itself

Abstract

The hepatitis B virus (HBV) regulatory protein X (HBx) activates gene expression from the HBV covalently closed circular DNA (cccDNA) genome. Interaction of HBx with the DDB1-CUL4-ROC1 (CRL4) E3 ligase is critical for this function. Using substrate-trapping proteomics, we identified the structural maintenance of chromosomes (SMC) complex proteins SMC5 and SMC6 as CRL4(HBx) substrates. HBx expression and HBV infection degraded the SMC5/6 complex in human hepatocytes in vitro and in humanized mice in vivo. HBx targets SMC5/6 for ubiquitylation by the CRL4(HBx) E3 ligase and subsequent degradation by the proteasome. Using a minicircle HBV (mcHBV) reporter system with HBx-dependent activity, we demonstrate that SMC5/6 knockdown, or inhibition with a dominant-negative SMC6, enhance HBx null mcHBV-Gluc gene expression. Furthermore, SMC5/6 knockdown rescued HBx-deficient HBV replication in human hepatocytes. These results indicate that a primary function of HBx is to degrade SMC5/6, which restricts HBV replication by inhibiting HBV gene expression.

Indexed as

ProteolysisAnimalsCell Cycle ProteinsChromosomal Proteins, Non-HistoneGene Expression Regulation, ViralGene Knockdown TechniquesHEK293 CellsHepatitis BHepatitis B virusHepatocytesHep G2 CellsHumansLiverMiceProtein BindingProteomicsCell Cycle ProteinsChromosomal Proteins, Non-Histonehepatitis B virus X proteinIL17RB protein, humanReceptors, Interleukin-17SMC5 protein, humanSMC6 protein, humanTrans-ActivatorsUbiquitin-Protein LigasesViral Regulatory and Accessory Proteins

Identifiers

PMID27626656
PMCPMC5078993
OpenAlexW2518924844

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.