scholarly journals TRIM Proteins and Their Roles in Antiviral Host Defenses

2018 ◽  
Vol 5 (1) ◽  
pp. 385-405 ◽  
Author(s):  
Michiel van Gent ◽  
Konstantin M.J. Sparrer ◽  
Michaela U. Gack
Keyword(s):  
Host Defense ◽  
Host Immunity ◽  
Innate Immune ◽  
Host Defenses ◽  
E3 Ligases ◽  
Cellular Processes ◽  
Cytokine Responses ◽  
Tripartite Motif ◽  
Trim Proteins

Tripartite motif (TRIM) proteins are a versatile family of ubiquitin E3 ligases involved in a multitude of cellular processes. Studies in recent years have demonstrated that many TRIM proteins play central roles in the host defense against viral infection. While some TRIM proteins directly antagonize distinct steps in the viral life cycle, others regulate signal transduction pathways induced by innate immune sensors, thereby modulating antiviral cytokine responses. Furthermore, TRIM proteins have been implicated in virus-induced autophagy and autophagy-mediated viral clearance. Given the important role of TRIM proteins in antiviral restriction, it is not surprising that several viruses have evolved effective maneuvers to neutralize the antiviral action of specific TRIM proteins. Here, we describe the major antiviral mechanisms of TRIM proteins as well as viral strategies to escape TRIM-mediated host immunity.

scholarly journals mSphere of Influence: Adenosine in Host Defense against Bacterial Pneumonia—Friend or Foe?

mSphere ◽  
2019 ◽  
Vol 4 (4) ◽  
Author(s):  
Elsa N. Bou Ghanem
Keyword(s):  
Host Defense ◽  
Bacterial Pneumonia ◽  
Pneumococcal Pneumonia ◽  
Respir Crit ◽  
Innate Immune ◽  
Immune Senescence ◽  
Host Defenses ◽  
Extracellular Adenosine ◽  
Gram Negative

ABSTRACT Elsa N. Bou Ghanem works in the field of innate immune senescence, inflammation, and host defense. In this mSphere of Influence article, she reflects on how “Adenosine A2B receptor deficiency promotes host defenses against Gram-negative bacterial pneumonia” by Barletta et al. (K. E. Barletta, R. E. Cagnina, M. D. Burdick, J. Linden, and B. Mehrad, Am J Respir Crit Care Med 186:1044–1050, 2012, https://doi.org/10.1164/rccm.201204-0622OC) impacted her own work examining the role of the extracellular adenosine pathway in neutrophil responses and host defense against pneumococcal pneumonia.

Functional interactions between ubiquitin E2 enzymes and TRIM proteins

2011 ◽  
Vol 434 (2) ◽  
pp. 309-319 ◽  
Author(s):  
Luisa M. Napolitano ◽  
Ellis G. Jaffray ◽  
Ronald T. Hay ◽  
Germana Meroni
Keyword(s):  
Coiled Coil ◽  
Specific Interactions ◽  
E3 Ligases ◽  
Cellular Processes ◽  
Coiled Coil Region ◽  
Physiological Relevance ◽  
Tripartite Motif ◽  
E2 Enzymes ◽  
Specific Reactions ◽  
Trim Proteins

The TRIM (tripartite motif) family of proteins is characterized by the presence of the tripartite motif module, composed of a RING domain, one or two B-box domains and a coiled-coil region. TRIM proteins are involved in many cellular processes and represent the largest subfamily of RING-containing putative ubiquitin E3 ligases. Whereas their role as E3 ubiquitin ligases has been presumed, and in several cases established, little is known about their specific interactions with the ubiquitin-conjugating E2 enzymes or UBE2s. In the present paper, we report a thorough screening of interactions between the TRIM and UBE2 families. We found a general preference of the TRIM proteins for the D and E classes of UBE2 enzymes, but we also revealed very specific interactions between TRIM9 and UBE2G2, and TRIM32 and UBE2V1/2. Furthermore, we demonstrated that the TRIM E3 activity is only manifest with the UBE2 with which they interact. For most specific interactions, we could also observe subcellular co-localization of the TRIM involved and its cognate UBE2 enzyme, suggesting that the specific selection of TRIM–UBE2 pairs has physiological relevance. Our findings represent the basis for future studies on the specific reactions catalysed by the TRIM E3 ligases to determine the fate of their targets.

Abstract 218: The Role of Novel Tripartite Motif Proteins in Sarcolemmal Membrane Repair

2014 ◽  
Vol 115 (suppl_1) ◽  
Author(s):  
Liubov V Gushchina ◽  
Jenna Alloush ◽  
Sayak Bhattacharya ◽  
Zhaobin Xu ◽  
Eric X Beck ◽  
...  
Keyword(s):  
Membrane Damage ◽  
Coiled Coil ◽  
Cardiac Cells ◽  
Acute Injury ◽  
Membrane Repair ◽  
Repair Capacity ◽  
E3 Ligases ◽  
Tripartite Motif ◽  
Trim Proteins

Tripartite motif (TRIM) proteins are a superfamily of coiled-coil-containing RING E3 ligases that function in many cellular processes, particularly in membrane repair pathways. Mitsugumin 53 (MG53) also known as TRIM72, is primary expressed in skeletal muscle and heart. Our experimental data confirm that during membrane damage, MG53 translocates to the injury site and acts as a molecular glue to reseal the damage area. The role of MG53 in membrane repair has been demonstrated in both in vitro studies using molecular approaches and in vivo using rodent wild type and knockout models. Thus, our data indicate that recombinant human MG53 protein can be directly applied as a therapeutic agent to increase the membrane repair capacity of many cell types, including cardiomyocytes during acute injury or in chronic disease progression. However, the precise mechanism and potential partners by which MG53 executes its membrane repair function are not completely understood. On the basis of the global TRIM family protein alignment, we hypothesize that there are other TRIM proteins that, alone or together with MG53, may facilitate repair by targeting the site of an injury. Moreover, data from our lab demonstrated that MG53 and these TRIM proteins can form homo- and hetero-oligomeric assemblies due to the presence of the coiled-coil region in these proteins and, further, that this may be necessary for the active membrane resealing process. Using E. coli protein expression methodology we can generate and isolate new TRIM recombinant proteins and test if these protein complexes are effective when applied externally to cardiac and non-cardiac cells. These novel proteins will also be tested for their pharmacokinetic properties to determine their efficacy in both acute and chronic applications. Our studies should increase our knowledge of the mechanisms controlling cardiac membrane repair and also provide novel therapeutic targets.

scholarly journals The role of SCF ubiquitin-ligase complex at the beginning of life

2019 ◽  
Vol 17 (1) ◽  
Author(s):  
Jiayan Xie ◽  
Yimei Jin ◽  
Guang Wang
Keyword(s):  
Cell Cycle ◽  
Ubiquitin Ligase ◽  
Cellular Proteins ◽  
Cell Cycle Regulators ◽  
Signal Transducers ◽  
E3 Ligases ◽  
Cellular Processes ◽  
Ubiquitin Ligase Complex ◽  
Scf Ubiquitin Ligase

AbstractAs the largest family of E3 ligases, the Skp1-cullin 1-F-box (SCF) E3 ligase complex is comprised of Cullins, Skp1 and F-box proteins. And the SCF E3 ubiquitin ligases play an important role in regulating critical cellular processes, which promote degradation of many cellular proteins, including signal transducers, cell cycle regulators, and transcription factors. We review the biological roles of the SCF ubiquitin-ligase complex in gametogenesis, oocyte-to-embryo transition, embryo development and the regulation for estrogen and progestin. We find that researches about the SCF ubiquitin-ligase complex at the beginning of life are not comprehensive, thus more in-depth researches will promote its eventual clinical application.

scholarly journals Role of Specialized Pro-Resolving Mediators in Modifying Host Defense and Decreasing Bacterial Virulence

Molecules ◽  
2021 ◽  
Vol 26 (22) ◽  
pp. 6970
Author(s):  
Julianne M. Thornton ◽  
Kingsley Yin
Keyword(s):  
Host Defense ◽  
Host Response ◽  
Tissue Repair ◽  
Defense Mechanisms ◽  
Neutrophil Migration ◽  
Bacterial Virulence ◽  
Innate Immune ◽  
Bioactive Fatty Acids ◽  
Insight Into

Bacterial infection activates the innate immune system as part of the host’s defense against invading pathogens. Host response to bacterial pathogens includes leukocyte activation, inflammatory mediator release, phagocytosis, and killing of bacteria. An appropriate host response requires resolution. The resolution phase involves attenuation of neutrophil migration, neutrophil apoptosis, macrophage recruitment, increased phagocytosis, efferocytosis of apoptotic neutrophils, and tissue repair. Specialized Pro-resolving Mediators (SPMs) are bioactive fatty acids that were shown to be highly effective in promoting resolution of infectious inflammation and survival in several models of infection. In this review, we provide insight into the role of SPMs in active host defense mechanisms for bacterial clearance including a new mechanism of action in which an SPM acts directly to reduce bacterial virulence.

scholarly journals Emerging RNA-binding roles in the TRIM family of ubiquitin ligases

2019 ◽  
Vol 400 (11) ◽  
pp. 1443-1464 ◽  
Author(s):  
Felix Preston Williams ◽  
Kevin Haubrich ◽  
Cecilia Perez-Borrajero ◽  
Janosch Hennig
Keyword(s):  
Ubiquitin Ligase ◽  
Cellular Differentiation ◽  
Potential Role ◽  
Rna Binding ◽  
Current Knowledge ◽  
E3 Ligases ◽  
Tumour Suppression ◽  
Ubiquitin Ligase Activity ◽  
Trim Proteins

Abstract TRIM proteins constitute a large, diverse and ancient protein family which play a key role in processes including cellular differentiation, autophagy, apoptosis, DNA repair, and tumour suppression. Mostly known and studied through the lens of their ubiquitination activity as E3 ligases, it has recently emerged that many of these proteins are involved in direct RNA binding through their NHL or PRY/SPRY domains. We summarise the current knowledge concerning the mechanism of RNA binding by TRIM proteins and its biological role. We discuss how RNA-binding relates to their previously described functions such as E3 ubiquitin ligase activity, and we will consider the potential role of enrichment in membrane-less organelles.

ROLE OF HOST DEFENSE PEPTIDES OF THE INNATE IMMUNE RESPONSE IN SEPSIS

Shock ◽  
2007 ◽  
pp. 1 ◽  
Author(s):  
Tobias Hirsch ◽  
Marie Metzig ◽  
Andreas Niederbichler ◽  
Hans-Ulrich Steinau ◽  
Elof Eriksson ◽  
...  
Keyword(s):  
Immune Response ◽  
Innate Immune Response ◽  
Host Defense ◽  
Innate Immune ◽  
Host Defense Peptides ◽  
Defense Peptides

scholarly journals NF-κB-Inducing Kinase Regulates Selected Gene Expression in the Nod2 Signaling Pathway

2006 ◽  
Vol 74 (4) ◽  
pp. 2121-2127 ◽  
Author(s):  
Qilin Pan ◽  
Vladimir Kravchenko ◽  
Alex Katz ◽  
Shuang Huang ◽  
Masayuki Ii ◽  
...  
Keyword(s):  
Host Defense ◽  
Innate Immune System ◽  
Muramyl Dipeptide ◽  
Innate Immune ◽  
Host Responses ◽  
Leucine Rich Repeat ◽  
Wild Type ◽  
Primary Explants ◽  
Repeat Domain

ABSTRACT The innate immune system surveys the extra- and intracellular environment for the presence of microbes. Among the intracellular sensors is a protein known as Nod2, a cytosolic protein containing a leucine-rich repeat domain. Nod2 is believed to play a role in determining host responses to invasive bacteria. A key element in upregulating host defense involves activation of the NF-κB pathway. It has been suggested through indirect studies that NF-κB-inducing kinase, or NIK, may be involved in Nod2 signaling. Here we have used macrophages derived from primary explants of bone marrow from wild-type mice and mice that either bear a mutation in NIK, rendering it inactive, or are derived from NIK−/− mice, in which the NIK gene has been deleted. We show that NIK binds to Nod2 and mediates induction of specific changes induced by the specific Nod2 activator, muramyl dipeptide, and that the role of NIK occurs in settings where both the Nod2 and TLR4 pathways are activated by their respective agonists. Specifically, we have linked NIK to the induction of the B-cell chemoattractant known as BLC and suggest that this chemokine may play a role in processes initiated by Nod2 activation that lead to improved host defense.

scholarly journals HERC Ubiquitin Ligases in Cancer

Cancers ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 1653
Author(s):  
Joan Sala-Gaston ◽  
Arturo Martinez-Martinez ◽  
Leonardo Pedrazza ◽  
L. Francisco Lorenzo-Martín ◽  
Rubén Caloto ◽  
...  
Keyword(s):  
Immune Responses ◽  
Tumor Suppressors ◽  
Molecular Mechanisms ◽  
Ubiquitin Ligases ◽  
Tumor Type ◽  
E3 Ligases ◽  
Cellular Processes ◽  
Damage Response ◽  
Herc Proteins

HERC proteins are ubiquitin E3 ligases of the HECT family. The HERC subfamily is composed of six members classified by size into large (HERC1 and HERC2) and small (HERC3–HERC6). HERC family ubiquitin ligases regulate important cellular processes, such as neurodevelopment, DNA damage response, cell proliferation, cell migration, and immune responses. Accumulating evidence also shows that this family plays critical roles in cancer. In this review, we provide an integrated view of the role of these ligases in cancer, highlighting their bivalent functions as either oncogenes or tumor suppressors, depending on the tumor type. We include a discussion of both the molecular mechanisms involved and the potential therapeutic strategies.

β-Amyloid is an Immunopeptide and Alzheimer's is an Autoimmune Disease

2021 ◽  
Vol 18 ◽  
Author(s):  
Donald F. Weaver
Keyword(s):  
Autoimmune Disease ◽  
Host Defense ◽  
Innate Immune System ◽  
Innate Immune ◽  
Brain Exposure ◽  
Host Defense Peptide ◽  
Amyloid Aβ ◽  
Β Amyloid ◽  
Definition Of

Background: As new biomolecular targets for Alzheimer’s disease (AD) emerge, there is a tendency to regard these as mutually exclusive and in competition, culminating in declarations that since the “amyloid hypothesis is dead” it needs to be replaced by completely different theories. However, given the well-described role of misfolding peptides, particularly β-amyloid (Aβ), in the pathogenesis of AD, the need for a broad-based conceptualization of AD, coalescing different theories into a single harmonized explanation emerges as a viable alternative. Incorporating protein aggregation mechanisms of AD into a more widely-encompassing immunopathic model of AD could accomplish such a goal – a goal which could be achieved by repositioning the role of Aβ as an immunopeptide. Conclusions: This review presents the concept that Aβ is an immunopeptide and that AD is an autoimmune disease in which Aβ is a key molecular player. Being a peptide with the capacity to alter immune function, Aβ is an immunopeptide; having both antimicrobial and immunomodulatory activities, Aβ is a host defense peptide; having most of the defining properties of cytokines, Aβ satisfies the broad definition of cytokine – the prototypic immunopeptide subtype. In addition to these immunoactivities, Aβ is also directly and independently cytotoxic to neurons by both necrotic and apoptotic mechanisms. Therefore, following brain exposure to immune-instigating stimuli, the innate immune system is activated, leading to the release of Aβ as an immunopeptide (functioning as a host defense peptide or cytokine), which subsequently inflicts a misdirected attack upon the host neurons – an autoimmune event.

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