scholarly journals The Role of the Host Ubiquitin System in Promoting Replication of Emergent Viruses

Viruses ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 369
Author(s):  
Karl M. Valerdi ◽  
Adam Hage ◽  
Sarah van van Tol ◽  
Ricardo Rajsbaum ◽  
Maria I. Giraldo
Keyword(s):  
Virus Replication ◽  
Defense Mechanism ◽  
Replication Cycle ◽  
Post Translational Modification ◽  
Cellular Functions ◽  
Emerging Viruses ◽  
Highly Pathogenic ◽  
Ubiquitin System ◽  
Pathogenic Viruses

Ubiquitination of proteins is a post-translational modification process with many different cellular functions, including protein stability, immune signaling, antiviral functions and virus replication. While ubiquitination of viral proteins can be used by the host as a defense mechanism by destroying the incoming pathogen, viruses have adapted to take advantage of this cellular process. The ubiquitin system can be hijacked by viruses to enhance various steps of the replication cycle and increase pathogenesis. Emerging viruses, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), flaviviruses like Zika and dengue, as well as highly pathogenic viruses like Ebola and Nipah, have the ability to directly use the ubiquitination process to enhance their viral-replication cycle, and evade immune responses. Some of these mechanisms are conserved among different virus families, especially early during virus entry, providing an opportunity to develop broad-spectrum antivirals. Here, we discuss the mechanisms used by emergent viruses to exploit the host ubiquitin system, with the main focus on the role of ubiquitin in enhancing virus replication.

scholarly journals SARS-CoV-2 Cellular Infection and Therapeutic Opportunities: Lessons Learned from Ebola Virus

Membranes ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 64
Author(s):  
Jordana Muñoz-Basagoiti ◽  
Daniel Perez-Zsolt ◽  
Jorge Carrillo ◽  
Julià Blanco ◽  
Bonaventura Clotet ◽  
...  
Keyword(s):  
Viral Entry ◽  
Ebola Virus ◽  
Lessons Learned ◽  
Productive Infection ◽  
Target Cells ◽  
Emerging Viruses ◽  
Highly Pathogenic ◽  
Life Threatening ◽  
Pathogenic Viruses ◽  
Cellular Machinery

Viruses rely on the cellular machinery to replicate and propagate within newly infected individuals. Thus, viral entry into the host cell sets up the stage for productive infection and disease progression. Different viruses exploit distinct cellular receptors for viral entry; however, numerous viral internalization mechanisms are shared by very diverse viral families. Such is the case of Ebola virus (EBOV), which belongs to the filoviridae family, and the recently emerged coronavirus SARS-CoV-2. These two highly pathogenic viruses can exploit very similar endocytic routes to productively infect target cells. This convergence has sped up the experimental assessment of clinical therapies against SARS-CoV-2 previously found to be effective for EBOV, and facilitated their expedited clinical testing. Here we review how the viral entry processes and subsequent replication and egress strategies of EBOV and SARS-CoV-2 can overlap, and how our previous knowledge on antivirals, antibodies, and vaccines against EBOV has boosted the search for effective countermeasures against the new coronavirus. As preparedness is key to contain forthcoming pandemics, lessons learned over the years by combating life-threatening viruses should help us to quickly deploy effective tools against novel emerging viruses.

scholarly journals Targeting Hedgehog Signalling through the Ubiquitylation Process: The Multiple Roles of the HECT-E3 Ligase Itch

Cells ◽  
2019 ◽  
Vol 8 (2) ◽  
pp. 98 ◽  
Author(s):  
Paola Infante ◽  
Ludovica Lospinoso Severini ◽  
Flavia Bernardi ◽  
Francesca Bufalieri ◽  
Lucia Di Marcotullio
Keyword(s):  
E3 Ligase ◽  
Multiple Roles ◽  
Post Translational Modification ◽  
Therapeutic Approaches ◽  
Cellular Functions ◽  
Hedgehog Signalling ◽  
Promising Target ◽  
Important Pathway ◽  
Multiple Levels

Hedgehog signalling (Hh) is a developmental conserved pathway strongly involved in cancers when deregulated. This important pathway is orchestrated by numerous regulators, transduces through distinct routes and is finely tuned at multiple levels. In this regard, ubiquitylation processes stand as essential for controlling Hh pathway output. Although this post-translational modification governs proteins turnover, it is also implicated in non-proteolytic events, thereby regulating the most important cellular functions. The HECT E3 ligase Itch, well known to control immune response, is emerging to have a pivotal role in tumorigenesis. By illustrating Itch specificities on Hh signalling key components, here we review the role of this HECT E3 ubiquitin ligase in suppressing Hh-dependent tumours and explore its potential as promising target for innovative therapeutic approaches.

ADP-ribosylation and intracellular traffic: an emerging role for PARP enzymes

2019 ◽  
Vol 47 (1) ◽  
pp. 357-370 ◽  
Author(s):  
Giovanna Grimaldi ◽  
Daniela Corda
Keyword(s):  
Intracellular Transport ◽  
Post Translational Modification ◽  
Cellular Functions ◽  
Intracellular Traffic ◽  
Adp Ribosylation ◽  
Cell Responses ◽  
Physiological Processes ◽  
Dependent Cell ◽  
Ribose Moiety

AbstractADP-ribosylation is an ancient and reversible post-translational modification (PTM) of proteins, in which the ADP-ribose moiety is transferred from NAD+ to target proteins by members of poly-ADP-ribosyl polymerase (PARP) family. The 17 members of this family have been involved in a variety of cellular functions, where their regulatory roles are exerted through the modification of specific substrates, whose identification is crucial to fully define the contribution of this PTM. Evidence of the role of the PARPs is now available both in the context of physiological processes and of cell responses to stress or starvation. An emerging role of the PARPs is their control of intracellular transport, as it is the case for tankyrases/PARP5 and PARP12. Here, we discuss the evidence pointing at this novel aspect of PARPs-dependent cell regulation.

scholarly journals Multi-Omics Integration Highlights the Role of Ubiquitination in CCl4-Induced Liver Fibrosis

2020 ◽  
Vol 21 (23) ◽  
pp. 9043
Author(s):  
Maria Mercado-Gómez ◽  
Fernando Lopitz-Otsoa ◽  
Mikel Azkargorta ◽  
Marina Serrano-Maciá ◽  
Sofia Lachiondo-Ortega ◽  
...  
Keyword(s):  
Liver Fibrosis ◽  
Cell Function ◽  
Gene Array ◽  
Matrix Proteins ◽  
Nuclear Antigen ◽  
Post Translational Modification ◽  
Physiological Processes ◽  
Ubiquitin System ◽  
Proliferating Cell

Liver fibrosis is the excessive accumulation of extracellular matrix proteins that occurs in chronic liver disease. Ubiquitination is a post-translational modification that is crucial for a plethora of physiological processes. Even though the ubiquitin system has been implicated in several human diseases, the role of ubiquitination in liver fibrosis remains poorly understood. Here, multi-omics approaches were used to address this. Untargeted metabolomics showed that carbon tetrachloride (CCl4)-induced liver fibrosis promotes changes in the hepatic metabolome, specifically in glycerophospholipids and sphingolipids. Gene ontology analysis of public deposited gene array-based data and validation in our mouse model showed that the biological process “protein polyubiquitination” is enriched after CCl4-induced liver fibrosis. Finally, by using transgenic mice expressing biotinylated ubiquitin (bioUb mice), the ubiquitinated proteome was isolated and characterized by mass spectrometry in order to unravel the hepatic ubiquitinated proteome fingerprint in CCl4-induced liver fibrosis. Under these conditions, ubiquitination appears to be involved in the regulation of cell death and survival, cell function, lipid metabolism, and DNA repair. Finally, ubiquitination of proliferating cell nuclear antigen (PCNA) is induced during CCl4-induced liver fibrosis and associated with the DNA damage response (DDR). Overall, hepatic ubiquitome profiling can highlight new therapeutic targets for the clinical management of liver fibrosis.

scholarly journals Role of the CM2 Protein in the Influenza C Virus Replication Cycle

2010 ◽  
Vol 85 (3) ◽  
pp. 1322-1329 ◽  
Author(s):  
T. Furukawa ◽  
Y. Muraki ◽  
T. Noda ◽  
E. Takashita ◽  
R. Sho ◽  
...  
Keyword(s):  
Virus Replication ◽  
Replication Cycle ◽  
Influenza C Virus ◽  
Virus Replication Cycle

Postsynaptic nanodomains generated by local palmitoylation cycles

2015 ◽  
Vol 43 (2) ◽  
pp. 199-204 ◽  
Author(s):  
Masaki Fukata ◽  
Atsushi Sekiya ◽  
Tatsuro Murakami ◽  
Norihiko Yokoi ◽  
Yuko Fukata
Keyword(s):  
Plasma Membrane ◽  
Protein Targeting ◽  
Scaffolding Protein ◽  
Dependent Manner ◽  
Membrane Domains ◽  
Post Translational Modification ◽  
Cellular Functions ◽  
Protein Palmitoylation ◽  
Specific Proteins

Precise regulation of protein assembly at specialized membrane domains is essential for diverse cellular functions including synaptic transmission. However, it is incompletely understood how protein clustering at the plasma membrane is initiated, maintained and controlled. Protein palmitoylation, a common post-translational modification, regulates protein targeting to the plasma membrane. Such modified proteins are enriched in these specialized membrane domains. In this review, we focus on palmitoylation of PSD-95, which is a major postsynaptic scaffolding protein and makes discrete postsynaptic nanodomains in a palmitoylation-dependent manner and discuss a determinant role of local palmitoylation cycles in creating highly localized hotspots at the membrane where specific proteins concentrate to organize functional domains.

scholarly journals Dengue virus non structural protein 1 disrupts the TGF-β/Smad signaling by utilizing E3 ligase Smurf2

2020 ◽  
Author(s):  
Anismrita Lahon ◽  
Ravi Arya ◽  
Vivek Kumar ◽  
Akhil Banerjea
Keyword(s):  
Dengue Virus ◽  
Virus Replication ◽  
Nuclear Translocation ◽  
E3 Ligase ◽  
Inhibitory Effect ◽  
Structural Protein ◽  
Cellular Functions ◽  
Smad Signaling

Abstract TGF-β signaling is tightly regulated to ensure cellular functions. Role of DENV on the TGF-β/Smad signaling has not been well established. Therefore, we aimed to study the association between DENV replication and TGF-β/Smad signaling. We observed impaired expression of Smad2/3/4 during DENV replication along with significant reduction in the expression of phosphorylated Smad3. Overexpression of Smad6/7 showed inhibitory effect on DENV replication. We observed DENV-NS1 not only physically interacts with Smad2/3/4 but also impaired their expression by utilizing Smurf2 E3 ligase. Co-immunoprecipitation of NS1 and Smurf2 suggests that NS1 may acts as a co-factor to escalate the lysosomal mediated degradation of Smads. Additionally we observed, NS1 is capable of blocking the nuclear translocation of Smad3 and thus further ensuring inhibition of Smad signaling. Therefore, our results confirm that DENV-NS1 interacts with Smads and reduces their expression that may favor in virus replication.

scholarly journals The Silent Partners

2020 ◽  
Author(s):  
Gal Almogy
Keyword(s):  
Hospital Admission ◽  
Health Systems ◽  
Emerging Viruses ◽  
Time And Space ◽  
Highly Pathogenic ◽  
Admission Rates ◽  
Current Health ◽  
Rapid Extinction ◽  
Pathogenic Viruses

Despite great advances in understanding the dynamics of viral epidemics, the emergence of rapidly spreading, highly pathogenic viruses remains a realistic and catastrophic possibility, which current health systems may not be able to fully contain. An intriguing feature in many recent zoonotic viral outbreaks is the presence of ‘superspreaders’, which are infected individuals that cause dramatically more new cases than the average. Here I study the effect of superspreaders on the early dynamics of emerging viruses that have not gained the capacity for efficient human-to-human transmission, i.e viruses with R0 < 1. I show that superspreaders have a higher chance of rapid extinction, but under ‘crowded’ conditions can lead to ‘outbreaks’, causing far more cases than regular viruses. Hence I suggest that outbreaks of highly pathogenic superspreaders are more likely when they coincide in time and space with an unrelated outbreak leading to increased hospital admission rates. These superspreader outbreaks may be difficult to detect, especially in the context of a different epidemic in progress, and can significantly affect mortality patterns observed in affected areas.

scholarly journals Ubiquitin-Specific Proteases: Players in Cancer Cellular Processes

2021 ◽  
Vol 14 (9) ◽  
pp. 848
Author(s):  
Lucas Cruz ◽  
Paula Soares ◽  
Marcelo Correia
Keyword(s):  
Protein Function ◽  
Deubiquitinating Enzymes ◽  
Post Translational Modification ◽  
Cellular Functions ◽  
Cellular Targets ◽  
Cellular Processes ◽  
Protein Ubiquitination ◽  
Damage Repair ◽  
Ubiquitin Molecule

Ubiquitination represents a post-translational modification (PTM) essential for the maintenance of cellular homeostasis. Ubiquitination is involved in the regulation of protein function, localization and turnover through the attachment of a ubiquitin molecule(s) to a target protein. Ubiquitination can be reversed through the action of deubiquitinating enzymes (DUBs). The DUB enzymes have the ability to remove the mono- or poly-ubiquitination signals and are involved in the maturation, recycling, editing and rearrangement of ubiquitin(s). Ubiquitin-specific proteases (USPs) are the biggest family of DUBs, responsible for numerous cellular functions through interactions with different cellular targets. Over the past few years, several studies have focused on the role of USPs in carcinogenesis, which has led to an increasing development of therapies based on USP inhibitors. In this review, we intend to describe different cellular functions, such as the cell cycle, DNA damage repair, chromatin remodeling and several signaling pathways, in which USPs are involved in the development or progression of cancer. In addition, we describe existing therapies that target the inhibition of USPs.

scholarly journals Role of VP30 Phosphorylation in the Ebola Virus Replication Cycle

2011 ◽  
Vol 204 (suppl_3) ◽  
pp. S934-S940 ◽  
Author(s):  
Miguel J. Martinez ◽  
Valentina A. Volchkova ◽  
Hervé Raoul ◽  
Nathalie Alazard-Dany ◽  
Olivier Reynard ◽  
...  
Keyword(s):  
Virus Replication ◽  
Ebola Virus ◽  
Replication Cycle ◽  
Virus Replication Cycle
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