scholarly journals The Role of Ubiquitination in NF-κB Signaling during Virus Infection

Viruses ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 145
Author(s):  
Kun Song ◽  
Shitao Li
Keyword(s):  
Viral Infection ◽  
Signaling Pathways ◽  
Control Cell ◽  
Viral Gene Expression ◽  
Nuclear Factor Κb ◽  
Viral Gene ◽  
Innate Defense ◽  
Signaling Axis ◽  
Signal Cascades

The nuclear factor κB (NF-κB) family are the master transcription factors that control cell proliferation, apoptosis, the expression of interferons and proinflammatory factors, and viral infection. During viral infection, host innate immune system senses viral products, such as viral nucleic acids, to activate innate defense pathways, including the NF-κB signaling axis, thereby inhibiting viral infection. In these NF-κB signaling pathways, diverse types of ubiquitination have been shown to participate in different steps of the signal cascades. Recent advances find that viruses also modulate the ubiquitination in NF-κB signaling pathways to activate viral gene expression or inhibit host NF-κB activation and inflammation, thereby facilitating viral infection. Understanding the role of ubiquitination in NF-κB signaling during viral infection will advance our knowledge of regulatory mechanisms of NF-κB signaling and pave the avenue for potential antiviral therapeutics. Thus, here we systematically review the ubiquitination in NF-κB signaling, delineate how viruses modulate the NF-κB signaling via ubiquitination and discuss the potential future directions.

scholarly journals Interplay Between SOX9, Wnt/β-Catenin and Androgen Receptor Signaling in Castration-Resistant Prostate Cancer

2019 ◽  
Vol 20 (9) ◽  
pp. 2066 ◽  
Author(s):  
Namrata Khurana ◽  
Suresh C. Sikka
Keyword(s):  
Prostate Cancer ◽  
Androgen Receptor ◽  
Signaling Pathways ◽  
Critical Role ◽  
Castration Resistant Prostate Cancer ◽  
Form Complex ◽  
Androgen Receptor Signaling ◽  
Castration Resistant ◽  
Signaling Axis

Androgen receptor (AR) signaling plays a key role not only in the initiation of prostate cancer (PCa) but also in its transition to aggressive and invasive castration-resistant prostate cancer (CRPC). However, the crosstalk of AR with other signaling pathways contributes significantly to the emergence and growth of CRPC. Wnt/β-catenin signaling facilitates ductal morphogenesis in fetal prostate and its anomalous expression has been linked with PCa. β-catenin has also been reported to form complex with AR and thus augment AR signaling in PCa. The transcription factor SOX9 has been shown to be the driving force of aggressive and invasive PCa cells and regulate AR expression in PCa cells. Furthermore, SOX9 has also been shown to propel PCa by the reactivation of Wnt/β-catenin signaling. In this review, we discuss the critical role of SOX9/AR/Wnt/β-catenin signaling axis in the development and progression of CRPC. The phytochemicals like sulforaphane and curcumin that can concurrently target SOX9, AR and Wnt/β-catenin signaling pathways in PCa may thus be beneficial in the chemoprevention of PCa.

Role of the avian retrovirus mRNA leader in expression: evidence for novel translational control

1986 ◽  
Vol 6 (2) ◽  
pp. 372-379
Author(s):  
R A Katz ◽  
B R Cullen ◽  
R Malavarca ◽  
A M Skalka
Keyword(s):  
Translational Control ◽  
Consensus Sequence ◽  
Viral Gene Expression ◽  
State Level ◽  
Viral Gene ◽  
Translational Initiation ◽  
Efficient Expression ◽  
Expression Characterization ◽  
Expression Evidence

Avian retroviral mRNAs contain a long 5' untranslated leader of approximately 380 nucleotides. The leader includes sequences required for viral replication and three AUG codons which precede the AUG codon used for translational initiation of the gag and env genes. We have used sensitive, quantitative assays of viral gene transcription and translation to analyze the role of this mRNA leader in viral gene expression. By substituting segments from related viruses, we had previously shown that the endogenous avian provirus ev-1 contained a defective leader segment (B. R. Cullen, A. M. Skalka, and G. Ju, Proc. Natl. Acad. Sci. USA 80:2946-2950, 1983). The sequence analysis presented here, followed by comparison with the nondefective ev-2 endogenous provirus segment, identified the critical changes at nucleotides 4 and 7 upstream of the initiator AUG. These differences do not alter the most conserved nucleotides within the consensus sequence which precedes eucaryotic initiation codons, but lie within a nine-nucleotide region that is otherwise highly conserved among avian retrovirus strains. Analysis of a series of deletion mutants indicated that other sequences within the leader are also required for efficient expression. Characterization of the altered transcripts demonstrated that the presence of the defective ev-1 segment or the deletion of a ca. 200-nucleotide leader segment did not affect the steady-state level or splicing efficiency of these mRNAs. Thus, we conclude that the reduced expression of these mRNAs is due to a translational deficiency. These results indicate that specific leader sequences, other than the previously identified consensus nucleotides which precede eucaryotic AUG initiator codons, can influence eucaryotic gene translation.

scholarly journals Norovirus infection results in assembly of virus-specific G3BP1 granules and evasion of eIF2α signaling

2018 ◽  
Author(s):  
Michèle Brocard ◽  
Valentina Iadevaia ◽  
Philipp Klein ◽  
Belinda Hall ◽  
Glenys Lewis ◽  
...  
Keyword(s):  
Host Cell ◽  
Rna Binding ◽  
Viral Gene Expression ◽  
Stress Granules ◽  
Viral Gene ◽  
Murine Norovirus ◽  
Initiation Factors ◽  
Protein Synthesis Machinery ◽  
Signaling Axis ◽  
Efficient Replication

ABSTRACTDuring viral infection, the accumulation of RNA replication intermediates or viral proteins imposes major stress on the host cell. In response, cellular stress pathways can rapidly impose defence mechanisms by shutting off the protein synthesis machinery, which viruses depend on, and triggering the accumulation of mRNAs into stress granules to limit the use of energy and nutrients. Because this threatens viral gene expression, viruses need to evade these pathways to propagate. Human norovirus is responsible for gastroenteritis outbreaks worldwide. Previously we showed that murine norovirus (MNV) regulates the activity of eukaryotic initiation factors (eIFs). Here we examined how MNV interacts with the eIF2α signaling axis controlling translation and stress granules accumulation. We show that while MNV infection represses host cell translation, it results in the assembly of virus-specific granules rather than stress granules. Further mechanistic analyses revealed that eIF2α signaling is uncoupled from translational stalling. Moreover the interaction of the RNA-binding protein G3BP1 with viral factors together with a redistribution of its cellular interacting partners could explain norovirus evasion of stress granules assembly. These results identify novel strategies by which norovirus ensure efficient replication propagation by manipulating the host stress response.

scholarly journals Oxymatrine Inhibits Bocavirus MVC Replication, Reduces Viral Gene Expression and Decreases Apoptosis Induced by Viral Infection

2019 ◽  
Vol 34 (1) ◽  
pp. 78-87 ◽  
Author(s):  
Yanqin Ding ◽  
Na Li ◽  
Jinhan Sun ◽  
Linran Zhang ◽  
Jianhui Guo ◽  
...  
Keyword(s):  
Gene Expression ◽  
Viral Infection ◽  
Viral Gene Expression ◽  
Viral Gene

scholarly journals Independent Contributions of Polyomavirus Middle T and Small T to the Regulation of Early and Late Gene Expression and DNA Replication

2006 ◽  
Vol 80 (15) ◽  
pp. 7295-7307 ◽  
Author(s):  
Li Chen ◽  
Xiaoyu Wang ◽  
Michele M. Fluck
Keyword(s):  
Gene Expression ◽  
Dna Replication ◽  
Signaling Pathways ◽  
Viral Gene Expression ◽  
Viral Gene ◽  
Phosphatidylinositol 3 Kinase ◽  
Late Gene Expression ◽  
Respective Contribution ◽  
Mouse Cells ◽  
The Individual

ABSTRACT We previously showed that murine polyomavirus mutants that lack both middle T (MT) and small T (ST) functions have a severe pleiotropic defect in early and late viral gene expression as well as genome amplification. The respective contribution of MT and ST to this phenotype was unclear. This work separates the roles of MT and ST in both permissive mouse cells and nonpermissive rat cells. It demonstrates for the first time a role for both proteins. To gain insight into the signaling pathways that might be required, we focused on MT and its mutants. The results show that each of the major MT signaling connections, Shc, phosphatidylinositol 3′-kinase, and phospholipase C γ1, could contribute in an additive way. Unexpectedly, a mutant lacking all these connections because the three major tyrosines had been converted to phenylalanine retained some activity. A mutant in which all six MT C-terminal tyrosines had been mutated was inactive. This suggests a novel signaling pathway for MT that uses the minor tyrosines. What is common to ST and the individual MT signaling pathways is the ability to signal to the polyomavirus enhancer, in particular to the crucial AP-1 and PEA3/ets binding sites. This connection explains the pleiotropy of MT and ST effects on transcription and DNA replication.

scholarly journals Enhancement of Hepatitis B Virus Replication by Its X Protein in Transgenic Mice

2002 ◽  
Vol 76 (5) ◽  
pp. 2579-2584 ◽  
Author(s):  
Zhenming Xu ◽  
T. S. Benedict Yen ◽  
Lanying Wu ◽  
Charles R. Madden ◽  
Wenjie Tan ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Transgenic Mice ◽  
Viral Gene Expression ◽  
Viral Gene ◽  
X Protein ◽  
Multifunctional Protein ◽  
Hbv Replication ◽  
B Virus

ABSTRACT Hepatitis B virus (HBV) X gene encodes a multifunctional protein that can regulate cellular signaling pathways, interact with cellular transcription factors, and induce hepatocellular oncogenesis. In spite of its diverse activities, the precise role of the X protein in the viral life cycle of HBV remains unclear. To investigate this question, we have produced transgenic mice that carry either the wild-type HBV genome or a mutated HBV genome incapable of expressing the 16.5-kDa X protein. Our results indicate that while the X protein is not absolutely essential for HBV replication or its maturation in transgenic mice, it can enhance viral replication, apparently by activating viral gene expression. These results demonstrate a transactivation role of the X protein in HBV replication in transgenic mice.

scholarly journals Epigenetic Repression of Herpes Simplex Virus Infection by the Nucleosome Remodeler CHD3

mBio ◽  
2014 ◽  
Vol 5 (1) ◽  
Author(s):  
Jesse H. Arbuckle ◽  
Thomas M. Kristie
Keyword(s):  
Gene Expression ◽  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Viral Infection ◽  
Host Cell ◽  
Viral Gene Expression ◽  
Viral Gene ◽  
Histone Marks ◽  
Viral Genomes ◽  
Simplex Virus

ABSTRACTUpon infection, the genome of herpes simplex virus is rapidly incorporated into nucleosomes displaying histone modifications characteristic of heterochromatic structures. The initiation of infection requires complex viral-cellular interactions that ultimately circumvent this repression by utilizing host cell enzymes to remove repressive histone marks and install those that promote viral gene expression. The reversion of repression and activation of viral gene expression is mediated by the cellular coactivator HCF-1 in association with histone demethylases and methyltransferases. However, the mechanisms and the components that are involved in the initial repression remain unclear. In this study, the chromatin remodeler chromodomain helicase DNA binding (CHD3) protein is identified as an important component of the initial repression of the herpesvirus genome. CHD3 localizes to early viral foci and suppresses viral gene expression. Depletion of CHD3 results in enhanced viral immediate early gene expression and an increase in the number of transcriptionally active viral genomes in the cell. Importantly, CHD3 can recognize the repressive histone marks that have been detected in the chromatin associated with the viral genome and this remodeler is important for ultimately reducing the levels of accessible viral genomes. A model is presented in which CHD3 represses viral infection in opposition to the actions of the HCF-1 coactivator complex. This dynamic, at least in part, determines the initiation of viral infection.IMPORTANCEChromatin modulation of herpesvirus infection is a dynamic process involving regulatory components that mediate suppression and those that promote viral gene expression and the progression of infection. The mechanisms by which the host cell employs the assembly and modulation of chromatin as an antiviral defense strategy against an invading herpesvirus remain unclear. This study defines a critical cellular component that mediates the initial repression of infecting HSV genomes and contributes to understanding the dynamics of this complex interplay between host cell and viral pathogen.

scholarly journals p-21-Activated kinase 1 mediates gastrin-stimulated proliferation in the colorectal mucosa via multiple signaling pathways

2013 ◽  
Vol 304 (6) ◽  
pp. G561-G567 ◽  
Author(s):  
Nhi Huynh ◽  
Mildred Yim ◽  
Jonathan Chernoff ◽  
Arthur Shulkes ◽  
Graham S. Baldwin ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
Control Cell ◽  
Growth Factor Signaling ◽  
Extracellular Signal Regulated Kinase ◽  
Colorectal Mucosa ◽  
Extracellular Signal ◽  
And Migration ◽  
Multiple Signaling

Gastrins, including amidated (Gamide) and glycine-extended (Ggly) forms, function as growth factors for the gastrointestinal mucosa. The p-21-activated kinase 1 (PAK1) plays important roles in growth factor signaling networks that control cell motility, proliferation, differentiation, and transformation. PAK1, activated by both Gamide and Ggly, mediates gastrin-stimulated proliferation and migration, and activation of β-catenin, in gastric epithelial cells. The aim of this study was to investigate the role of PAK1 in the regulation by gastrin of proliferation in the normal colorectal mucosa in vivo. Mucosal proliferation was measured in PAK1 knockout (PAK1 KO) mice by immunohistochemistry. The expression of phosphorylated and unphosphorylated forms of the signaling molecules PAK1, extracellular signal-regulated kinase (ERK), and protein kinase B (AKT), and the expression of β-catenin and its downstream targets c-Myc and cyclin D1, were measured in gastrin knockout (Gas KO) and PAK1 KO mice by Western blotting. The expression and activation of PAK1 are decreased in Gas KO mice, and these decreases are associated with reduced activation of ERK, AKT, and β-catenin. Proliferation in the colorectal mucosa of PAK1 KO mice is reduced, and the reduction is associated with reduced activation of ERK, AKT, and β-catenin. In compensation, antral gastrin mRNA and serum gastrin concentrations are increased in PAK1 KO mice. These results indicate that PAK1 mediates the stimulation of colorectal proliferation by gastrins via multiple signaling pathways involving activation of ERK, AKT, and β-catenin.

scholarly journals p38 mitogen-activated protein kinase is crucial for bovine papillomavirus type-1 transformation of equine fibroblasts

2011 ◽  
Vol 92 (8) ◽  
pp. 1778-1786 ◽  
Author(s):  
ZhengQiang Yuan ◽  
Elizabeth A. Gault ◽  
M. Saveria Campo ◽  
Lubna Nasir
Keyword(s):  
Protein Kinase ◽  
Viral Gene Expression ◽  
Cellular Transformation ◽  
Mitogen Activated Protein Kinase ◽  
Viral Gene ◽  
Bovine Papillomavirus ◽  
Equine Sarcoid ◽  
Mitogen Activated Protein

Equine sarcoids represent the most common skin tumours in equids worldwide, characterized by extensive invasion and infiltration of lymphatics, rare regression and high recurrence after surgical intervention. Bovine papillomavirus type-1 (BPV-1) and less commonly BPV-2 are the causative agents of the diseases. It has been demonstrated that BPV-1 viral gene expression is necessary for maintaining the transformation phenotype. However, the underlying mechanism for BPV-1 transformation remains largely unknown, and the cellular factors involved in transformation are not fully understood. Previously mitogen-activated protein kinase (MAPK) signalling pathway has been shown to be important for cellular transformation. This study investigated the role of p38 MAPK (p38) in the transformation of equine fibroblasts by BPV-1. Elevated expression of phosphorylated p38 was observed in BPV-1 expressing fibroblasts due to the expression of BPV-1 E5 and E6. The phosphorylation of the MK2 kinase, a substrate of p38, was also enhanced. Inhibition of p38 activity by its selective inhibitor SB203580 changed cell morphology, reduced the proliferation of sarcoid fibroblasts and inhibited cellular invasiveness, indicating the indispensable role of p38 in BPV-1 transformation of equine fibroblasts. These findings provide new insights into the pathogenesis of equine sarcoids and suggest that p38 could be a potential target for equine sarcoid therapy.

scholarly journals Plasmodium falciparum–infected erythrocytes induce NF-κB regulated inflammatory pathways in human cerebral endothelium

Blood ◽  
2009 ◽  
Vol 114 (19) ◽  
pp. 4243-4252 ◽  
Author(s):  
Abhai K. Tripathi ◽  
Wei Sha ◽  
Vladimir Shulaev ◽  
Monique F. Stins ◽  
David J. Sullivan
Keyword(s):  
Plasmodium Falciparum ◽  
Human Brain ◽  
Cerebral Malaria ◽  
Nuclear Factor Κb ◽  
Brain Endothelium ◽  
Innate Defense ◽  
Inflammatory Pathways ◽  
Activation Cascade ◽  
The Brain

Abstract Cerebral malaria is a severe multifactorial condition associated with the interaction of high numbers of infected erythrocytes to human brain endothelium without invasion into the brain. The result is coma and seizures with death in more than 20% of cases. Because the brain endothelium is at the interface of these processes, we investigated the global gene responses of human brain endothelium after the interaction with Plasmodium falciparum–infected erythrocytes with either high- or low-binding phenotypes. The most significantly up-regulated transcripts were found in gene ontology groups comprising the immune response, apoptosis and antiapoptosis, inflammatory response, cell-cell signaling, and signal transduction and nuclear factor κB (NF-κB) activation cascade. The proinflammatory NF-κB pathway was central to the regulation of the P falciparum–modulated endothelium transcriptome. The proinflammatory molecules, for example, CCL20, CXCL1, CXCL2, IL-6, and IL-8, were increased more than 100-fold, suggesting an important role of blood-brain barrier (BBB) endothelium in the innate defense during P falciparum–infected erythrocyte (Pf-IRBC) sequestration. However, some of these diffusible molecules could have reversible effects on brain tissue and thus on neurologic function. The inflammatory pathways were validated by direct measurement of proteins in brain endothelial supernatants. This study delineates the strong inflammatory component of human brain endothelium contributing to cerebral malaria.

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