scholarly journals Specificity in Ubiquitination Triggered by Virus Infection

2020 ◽  
Vol 21 (11) ◽  
pp. 4088 ◽  
Author(s):  
Haidong Gu ◽  
Behdokht Jan Fada
Keyword(s):  
Host Interactions ◽  
Ubiquitinated Proteins ◽  
Virus Life Cycle ◽  
Ubiquitin System ◽  
Ubiquitin Binding ◽  
Lysine Residues ◽  
Ubiquitin Binding Domain ◽  
Ubiquitin Moiety ◽  
The Rich

Ubiquitination is a prominent posttranslational modification, in which the ubiquitin moiety is covalently attached to a target protein to influence protein stability, interaction partner and biological function. All seven lysine residues of ubiquitin, along with the N-terminal methionine, can each serve as a substrate for further ubiquitination, which effectuates a diverse combination of mono- or poly-ubiquitinated proteins with linear or branched ubiquitin chains. The intricately composed ubiquitin codes are then recognized by a large variety of ubiquitin binding domain (UBD)-containing proteins to participate in the regulation of various pathways to modulate the cell behavior. Viruses, as obligate parasites, involve many aspects of the cell pathways to overcome host defenses and subjugate cellular machineries. In the virus-host interactions, both the virus and the host tap into the rich source of versatile ubiquitination code in order to compete, combat, and co-evolve. Here, we review the recent literature to discuss the role of ubiquitin system as the infection progresses in virus life cycle and the importance of ubiquitin specificity in the regulation of virus-host relation.

scholarly journals Role of the ubiquitin-binding domain of Polη in Rad18-independent translesion DNA synthesis in human cell extracts

2010 ◽  
Vol 38 (19) ◽  
pp. 6456-6465 ◽  
Author(s):  
Valérie Schmutz ◽  
Régine Janel-Bintz ◽  
Jérôme Wagner ◽  
Denis Biard ◽  
Naoko Shiomi ◽  
...  
Keyword(s):  
Dna Synthesis ◽  
Human Cell ◽  
Binding Domain ◽  
Translesion Dna Synthesis ◽  
Cell Extracts ◽  
Ubiquitin Binding ◽  
Ubiquitin Binding Domain ◽  
Translesion Dna

scholarly journals The role of spartin and its novel ubiquitin binding region in DALIS occurrence

2014 ◽  
Vol 25 (8) ◽  
pp. 1355-1365 ◽  
Author(s):  
Amelia B. Karlsson ◽  
Jacqueline Washington ◽  
Valentina Dimitrova ◽  
Christopher Hooper ◽  
Alexander Shekhtman ◽  
...  
Keyword(s):  
Autosomal Recessive ◽  
Resonance Spectroscopy ◽  
Spastic Paraplegia ◽  
Binding Region ◽  
Hairpin Rna ◽  
Multifunctional Protein ◽  
Ubiquitin Binding ◽  
Ubiquitin Binding Domain ◽  
Key Residues

Troyer syndrome is an autosomal recessive hereditary spastic paraplegia (HSP) caused by frameshift mutations in the SPG20 gene that results in a lack of expression of the truncated protein. Spartin is a multifunctional protein, yet only two conserved domains—a microtubule-interacting and trafficking domain and a plant-related senescence domain involved in cytokinesis and mitochondrial physiology, respectively—have been defined. We have shown that overexpressed spartin binds to the Ile44 hydrophobic pocket of ubiquitin, suggesting spartin might contain a ubiquitin-binding domain. In the present study, we demonstrate that spartin contributes to the formation of dendritic aggresome-like induced structures (DALIS) through a unique ubiquitin-binding region (UBR). Using short hairpin RNA, we knocked down spartin in RAW264.7 cells and found that DALIS frequency decreased; conversely, overexpression of spartin increased the percentage of cells containing DALIS. Using nuclear magnetic resonance spectroscopy, we characterized spartin's UBR and defined the UBR's amino acids that are key for ubiquitin binding. We also found that spartin, via the UBR, binds Lys-63–linked ubiquitin chains but does not bind Lys-48–linked ubiquitin chains. Finally, we demonstrate that spartin's role in DALIS formation depends on key residues within its UBR.

scholarly journals Animals in the Zika virus life cycle: what to expect from megadiverse Latin American countries

2016 ◽  
Author(s):  
Marina Galvão Bueno ◽  
Nádia Martinez ◽  
Lívia Abdala ◽  
Claudia Nunes Duarte dos Santos ◽  
Marcia Chame
Keyword(s):  
Latin American ◽  
Zika Virus ◽  
Epidemiological Studies ◽  
Sylvatic Cycle ◽  
News Stories ◽  
Virus Life Cycle ◽  
History Of ◽  
The Rich ◽  
Latin American Countries

ABSTRACTZika virus (ZIKV) was first isolated in 1947 in primates in Uganda, West Africa. The virus remained confined to the equatorial regions of Africa and Asia, cycling between infecting monkeys, arboreal mosquitoes, and occasional humans. The ZIKV Asiatic strain was probably introduced into Brazil in 2013. In the current critical human epidemic in the Americas, ZIKV is transmitted primarily by Aedes aegypti mosquitoes, especially where the human population density is combined with poor sanitation. Presently, ZIKV is in contact with the rich biodiversity in all Brazilian biomes, bordering on other Latin American countries. Infections in Brazilian primates have been reported recently, but the overall impact of this virus on wildlife in the Americas is still unknown. The current epidemic in the Americas requires knowledge on the role of mammals, especially non-human primates, in ZIKV transmission to humans. The article discusses the available data on ZIKV in host animals, besides issues of biodiversity, rapid environmental change, and impact on human health in megadiverse Latin American countries. The authors reviewed scientific articles and recent news stories on ZIKV in animals, showing that 47 animal species from three orders (mammals, reptiles, and birds) have been investigated for the potential to establish a sylvatic cycle. The review aims to contribute to epidemiological studies and the knowledge on the natural history of ZIKV. The article concludes with questions that require urgent attention in epidemiological studies involving wildlife in order to understand their role as ZIKV hosts and to effectively control the epidemic.

scholarly journals Doa1 Is a Cdc48 Adapter That Possesses a Novel Ubiquitin Binding Domain

2006 ◽  
Vol 26 (3) ◽  
pp. 822-830 ◽  
Author(s):  
James E. Mullally ◽  
Tatiana Chernova ◽  
Keith D. Wilkinson
Keyword(s):  
Molecular Chaperone ◽  
Physiological Role ◽  
Binding Domain ◽  
Cellular Functions ◽  
Aaa Atpase ◽  
Functional Conservation ◽  
Ubiquitinated Proteins ◽  
Ubiquitin Binding ◽  
Ubiquitin Binding Domain ◽  
Mammalian Homologue

ABSTRACT Cdc48 (p97/VCP) is an AAA-ATPase molecular chaperone whose cellular functions are facilitated by its interaction with ubiquitin binding cofactors (e.g., Npl4-Ufd1 and Shp1). Several studies have shown that Saccharomyces cerevisiae Doa1 (Ufd3/Zzz4) and its mammalian homologue, PLAA, interact with Cdc48. However, the function of this interaction has not been determined, nor has a physiological link between these proteins been demonstrated. Herein, we demonstrate that Cdc48 interacts directly with the C-terminal PUL domain of Doa1. We find that Doa1 possesses a novel ubiquitin binding domain (we propose the name PFU domain, for PLAA family ubiquitin binding domain), which appears to be necessary for Doa1 function. Our data suggest that the PUL and PFU domains of Doa1 promote the formation of a Doa1-Cdc48-ubiquitin ternary complex, potentially allowing for the recruitment of ubiquitinated proteins to Cdc48. DOA1 and CDC48 mutations are epistatic, suggesting that their interaction is physiologically relevant. Lastly, we provide evidence of functional conservation within the PLAA family by showing that a human-yeast chimera binds to ubiquitin and complements doa1Δ phenotypes in yeast. Combined, our data suggest that Doa1 plays a physiological role as a ubiquitin binding cofactor of Cdc48 and that human PLAA may play an analogous role via its interaction with p97/VCP.

scholarly journals The Role of Deubiquitinases in Oncovirus and Host Interactions

2019 ◽  
Vol 2019 ◽  
pp. 1-9 ◽  
Author(s):  
Yueshuo Li ◽  
Feng Shi ◽  
Jianmin Hu ◽  
Longlong Xie ◽  
Ann M. Bode ◽  
...  
Keyword(s):  
Life Cycle ◽  
Signaling Pathways ◽  
Protein Function ◽  
Deubiquitinating Enzymes ◽  
Antiviral Signaling ◽  
Host Interactions ◽  
Cellular Processes ◽  
Ubiquitin System ◽  
Almost All

Infection-related cancer comprises one-sixth of the global cancer burden. Oncoviruses can directly or indirectly contribute to tumorigenesis. Ubiquitination is a dynamic and reversible posttranslational modification that participates in almost all cellular processes. Hijacking of the ubiquitin system by viruses continues to emerge as a central theme around the viral life cycle. Deubiquitinating enzymes (DUBs) maintain ubiquitin homeostasis by removing ubiquitin modifications from target proteins, thereby altering protein function, stability, and signaling pathways, as well as acting as key mediators between the virus and its host. In this review, we focus on the multiple functions of DUBs in RIG-I-like receptors (RLRs) and stimulator of interferon genes (STING)-mediated antiviral signaling pathways, oncoviruses regulation of NF-κB activation, oncoviral life cycle, and the potential of DUB inhibitors as therapeutic strategies.

scholarly journals Selective Autophagy by Close Encounters of the Ubiquitin Kind

Cells ◽  
2020 ◽  
Vol 9 (11) ◽  
pp. 2349 ◽  
Author(s):  
Anna Vainshtein ◽  
Paolo Grumati
Keyword(s):  
Protein Aggregates ◽  
Degradation Process ◽  
Eukaryotic Cells ◽  
Post Translational Modifications ◽  
Selective Autophagy ◽  
Close Encounters ◽  
Ubiquitin Binding ◽  
Ubiquitin Binding Domain ◽  
Cellular Turnover

Autophagy, a bulk degradation process within eukaryotic cells, is responsible for cellular turnover and nutrient liberation during starvation. Increasing evidence indicate that this process can be extremely discerning. Selective autophagy segregates and eliminates protein aggregates, damaged organelles, and invading organisms. The specificity of this process is largely mediated by post-translational modifications (PTMs), which are recognized by autophagy receptors. These receptors grant autophagy surgical precision in cargo selection, where only tagged substrates are engulfed within autophagosomes and delivered to the lysosome for proteolytic breakdown. A growing number of selective autophagy receptors have emerged including p62, NBR1, OPTN, NDP52, TAX1BP1, TOLLIP, and more continue to be uncovered. The most well-documented PTM is ubiquitination and selective autophagy receptors are equipped with a ubiquitin binding domain and an LC3 interacting region which allows them to physically bridge cargo to autophagosomes. Here, we review the role of ubiquitin and ubiquitin-like post-translational modifications in various types of selective autophagy.

scholarly journals A Novel Epigenetic Regulator ZRF1: Insight into Its Functions in Plants

Genes ◽  
2021 ◽  
Vol 12 (8) ◽  
pp. 1245
Author(s):  
Jing Feng ◽  
Yahui Gao ◽  
Kun Wang ◽  
Mingguo Jiang
Keyword(s):  
Target Genes ◽  
Higher Plants ◽  
Research Progress ◽  
Related Factor ◽  
Histone H2a ◽  
Epigenetic Regulator ◽  
Ubiquitin Binding ◽  
Ubiquitin Binding Domain ◽  
Insight Into

Recently, Zuotin-related factor 1 (ZRF1), an epigenetic regulator, was found to be involved in transcriptional regulation. In animals and humans, ZRF1 specifically binds to monoubiquitinated histone H2A through a ubiquitin-binding domain and derepresses Polycomb target genes at the beginning of cellular differentiation. In addition, ZRF1 can work as a tumor suppressor. According to bioinformatics analysis, ZRF1 homologs are widely found in plants. However, the current studies on ZRF1 in higher plants are limited and few in-depth studies of its functions have been reported. In this review, we aim to summarize the key role of AtZRF1a/b in Arabidopsis thaliana growth and development, as well as the research progress in this field in recent years.

Role of Methylglyoxal in Diabetic Cardiovascular and Kidney Diseases: Insights from Basic Science for Application into Clinical Practice

2018 ◽  
Vol 24 (26) ◽  
pp. 3072-3083 ◽  
Author(s):  
Sowndramalingam Sankaralingam ◽  
Angham Ibrahim ◽  
MD Mizanur Rahman ◽  
Ali H. Eid ◽  
Shankar Munusamy
Keyword(s):  
Therapeutic Strategy ◽  
Kidney Diseases ◽  
Vascular Dysfunction ◽  
Dicarbonyl Compound ◽  
Renal Complications ◽  
Lysine Residues ◽  
Patients With Diabetes ◽  
Prevalence Of Diabetes Mellitus

Background: The incidence and prevalence of diabetes mellitus are increasing globally at alarming rates. Cardiovascular and renal complications are the major cause of morbidity and mortality in patients with diabetes. Methylglyoxal (MG) - a highly reactive dicarbonyl compound – is increased in patients with diabetes and has been implicated to play a detrimental role in the etiology of cardiovascular and renal complications. Derived from glucose, MG binds to arginine and lysine residues in proteins, and the resultant end products serve as surrogate markers of MG generation in vivo. Under normal conditions, MG is detoxified by the enzyme glyoxalase 1 (Glo1), using reduced glutathione as a co-factor. Elevated levels of MG is known to cause endothelial and vascular dysfunction, oxidative stress and atherosclerosis; all of which are risk factors for cardiovascular diseases. Moreover, MG has also been shown to cause pathologic structural alterations and impair kidney function. Conversely, MG scavengers (such as N-acetylcysteine, aminoguanidine or metformin) or Nrf2/Glo1 activators (such as trans-resveratrol / hesperetin) are shown to be useful in preventing MG-induced cardiovascular and renal complications in diabetes. However, clinical evidence supporting the MG lowering properties of these agents are limited and hence, need further investigation. Conclusion: Reducing MG levels directly using scavengers or indirectly via activation of Nrf2/Glo1 may serve as a novel and potent therapeutic strategy to counter the deleterious effects of MG in diabetic complications.

Generating Prosperity for Working Families in Affluent Countries

2018 ◽  
Keyword(s):  
Economic Growth ◽  
Real Income ◽  
Living Standards ◽  
Financial Strain ◽  
Inclusive Growth ◽  
Working Families ◽  
The Rich ◽  
Rich Countries ◽  
Analysis Of Performance

This book addresses the central challenge facing rich countries: how to ensure that ordinary working families see their living standards and the prospects for their children improve rather than stagnate over time. It presents the findings from a comprehensive analysis of performance over recent decades across the rich countries of the OECD, in terms of real income growth around and below the middle. It relates this performance to overall economic growth, exploring why these often diverge substantially, and to the different models of capitalism or economic growth embedded in different countries. In-depth comparative and UK-focused analyses also focus on wages and the labour market and on the role of redistribution. Going beyond income, other indicators and aspects of living standards are also incorporated including non-monetary indicators of deprivation and financial strain, wealth and its distribution, and intergenerational mobility. By looking across this broad canvas, the book teases out how ordinary households have fared in recent decades in these critically important respects, and how that should inform the quest for inclusive growth and prosperity.

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