ELM—the Eukaryotic Linear Motif resource—2024 update

Nucleic Acids Research, Journal Year: 2023, Volume and Issue: 52(D1), P. D442 - D455

Published: Nov. 14, 2023

Abstract Short Linear Motifs (SLiMs) are the smallest structural and functional components of modular eukaryotic proteins. They also most abundant, especially when considering post-translational modifications. As well as being found throughout cell part regulatory processes, SLiMs extensively mimicked by intracellular pathogens. At heart Eukaryotic Motif (ELM) Resource is a representative (not comprehensive) database. The ELM entries created growing community skilled annotators provide an introduction to linear motif functionality for biomedical researchers. 2024 update includes 346 novel instances in areas ranging from innate immunity both protein RNA degradation systems. In total, 39 classes newly annotated motifs have been added, another 17 existing updated release now 356 incorporating 4283 individual manually curated 4274 scientific publications including >700 links experimentally determined 3D structures. recent development, InterPro module resource data. available at: http://elm.eu.org.

Language: Английский

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The multiple roles of interferon regulatory factor family in health and disease

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: Oct. 9, 2024

Interferon Regulatory Factors (IRFs), a family of transcription factors, profoundly influence the immune system, impacting both physiological and pathological processes. This review explores diverse functions nine mammalian IRF members, each featuring conserved domains essential for interactions with other factors cofactors. These allow IRFs to modulate broad spectrum processes, encompassing host defense, response, cell development. Conversely, their pivotal role in regulation implicates them pathophysiology various diseases, such as infectious autoimmune disorders, metabolic cancers. In this context, display dichotomous nature, functioning tumor suppressors promoters, contingent upon specific disease milieu. Post-translational modifications IRFs, including phosphorylation ubiquitination, play crucial modulating function, stability, activation. As prospective biomarkers therapeutic targets, present promising opportunities intervention. Further research is needed elucidate precise mechanisms governing regulation, potentially pioneering innovative strategies, particularly cancer treatment, where equilibrium activities paramount importance.

Language: Английский

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Epigenetic Control of Innate Immunity: Consequences of Acute Respiratory Virus Infection

Viruses, Journal Year: 2024, Volume and Issue: 16(2), P. 197 - 197

Published: Jan. 27, 2024

Infections caused by acute respiratory viruses induce a systemic innate immune response, which can be measured the increased levels of expression inflammatory genes in cells. There is growing evidence that these viral infections, alongside transient transcriptomic responses, epigenetic remodeling as part such DNA methylation and histone modifications, might persist after infection cleared. In this article, we first review primary mechanisms context immunity inflammation, are crucial for regulation response to infections. Next, delve into existing knowledge concerning impact virus infections on epigenome, focusing Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), Influenza A Virus (IAV), Syncytial (RSV). Finally, offer perspectives potential consequences virus-induced open questions field currently under investigation.

Language: Английский

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Bacteriophage DNA induces an interrupted immune response during phage therapy in a chicken model

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: March 13, 2024

One of the hopes for overcoming antibiotic resistance crisis is use bacteriophages to combat bacterial infections, so-called phage therapy. This therapeutic approach generally believed be safe humans and animals as phages should infect only prokaryotic cells. Nevertheless, recent studies suggested that might recognized by eukaryotic cells, inducing specific cellular responses. Here we show in chickens infected with Salmonella enterica treated a cocktail, are initially animal cells viruses, however, cGAS-STING pathway (one two major pathways innate antiviral response) blocked at stage IRF3 transcription factor phosphorylation. inhibition due inability RNA polymerase III recognize DNA produce dsRNA molecules which necessary stimulate large protein complex indispensable phosphorylation, indicating mechanism response impairment.

Language: Английский

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Foot-and-mouth disease virus VP1 degrades YTHDF2 through autophagy to regulate IRF3 activity for viral replication

Autophagy, Journal Year: 2024, Volume and Issue: 20(7), P. 1597 - 1615

Published: March 22, 2024

Many viruses, including foot-and-mouth disease virus (FMDV), can promote the degradation of host proteins through macroautophagy/autophagy, thereby promoting viral replication. However, regulatory mechanism between autophagy and innate immune responses is not fully understood during FMDV infection. Here, we found that GTPBP4/NOG1 (GTP binding protein 4) a negative regulator responses. GTPBP4 deficiency promotes antiviral response, resulting in ability to Meanwhile, GTPBP4-deficient mice are more resistant To antagonize host's immunity, structural VP1 expression GTPBP4, 209th site responsible for this effect. Mechanically, infection interacts with degrades YTHDF2 (YTH N6-methyladenosine RNA F2) an AKT-MTOR-dependent pathway, increase mRNA levels. Increased inhibits IRF3 Ifnb/Ifn-β promoter, suppressing FMDV-induced type I interferon production. In conclusion, our study revealed underlying how negatively regulates immunity which would contribute understanding regulation function

Language: Английский

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Targeting transcription factors for therapeutic benefit in rheumatoid arthritis

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14

Published: June 29, 2023

Rheumatoid arthritis (RA) is a destructive inflammatory autoimmune disease that causes pain and disability. Many of the currently available drugs for treating RA patients are aimed at halting progression alleviating inflammation. Further, some these treatment options have drawbacks, including recurrence adverse effects due to long-term use. These inefficiencies created need different approach RA. Recently, focus has shifted direct targeting transcription factors (TFs), as they play vital role in pathogenesis RA, activating key cytokines, chemokines, adhesion molecules, enzymes. In light this, synthetic natural compounds being explored target TFs or their signaling pathways This review discusses four inflammation, namely NF-κB, STATs, AP-1 IRFs, potential targeted treat

Language: Английский

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Host Innate Antiviral Response to Influenza A Virus Infection: From Viral Sensing to Antagonism and Escape

Pathogens, Journal Year: 2024, Volume and Issue: 13(7), P. 561 - 561

Published: July 3, 2024

Influenza virus possesses an RNA genome of single-stranded, negative-sensed, and segmented configuration. causes acute respiratory disease, commonly known as the "flu" in humans. In some individuals, flu can lead to pneumonia distress syndrome. A (IAV) is most significant because it recurring seasonal epidemics, occasional pandemics, zoonotic outbreaks human populations, globally. The host innate immune response IAV infection plays a critical role sensing, preventing, clearing well disease pathology. Host cells sense through multiple receptors mechanisms, which culminate induction concerted antiviral creation state, inhibits clears from cells. However, antagonizes escapes many steps by different mechanisms. Herein, we review those viral This covers aspects response, i.e., (1) sensing incoming particles, (2) activation downstream signaling pathways, (3) expression interferon-stimulated genes, (4) antagonism escape.

Language: Английский

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Interference without interferon: interferon-independent induction of interferon-stimulated genes and its role in cellular innate immunity

mBio, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 20, 2024

ABSTRACT Interferons (IFNs) are multifaceted proteins that play pivotal roles in orchestrating robust antiviral immune responses and modulating the intricate landscape of host immunity. The major signaling pathway activated by IFNs is JAK/STAT (Janus kinase/signal transducer activator transcription) pathway, which leads to transcription a battery genes, collectively known as IFN-stimulated genes (ISGs). While well-established role coordinating innate response against viral infections widely acknowledged, recent years have provided more distinct comprehension functional significance attributed non-canonical, IFN-independent induction ISGs. In this review, we summarize non-conventional pathways ISG induction. These alternative offer new avenues for developing strategies or immunomodulation various diseases.

Language: Английский

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Viral Circular RNAs and Their Possible Roles in Virus-Host Interaction

Frontiers in Immunology, Journal Year: 2022, Volume and Issue: 13

Published: June 17, 2022

Circular RNAs (circRNAs) as novel regulatory molecules have been recognized in diverse species, including viruses. The virus-derived circRNAs play various roles the host biological process and life cycle of This review summarized from DNA RNA viruses discussed biogenesis viral circRNAs, potential their future perspective. will elaborate on new insights gained encoded during virus infection.

Language: Английский

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Phase Separation: The Robust Modulator of Innate Antiviral Signaling and SARS-CoV-2 Infection

Pathogens, Journal Year: 2023, Volume and Issue: 12(2), P. 243 - 243

Published: Feb. 3, 2023

SARS-CoV-2 has been a pandemic threat to human health and the worldwide economy, but efficient treatments are still lacking. Type I III interferons essential for controlling viral infection, indicating that antiviral innate immune signaling is critical defense against infection. Phase separation, one of basic molecular processes, governs multiple cellular activities, such as cancer progression, microbial transduction. Notably, recent studies suggest phase separation regulates RLR cGAS–STING pathways. Moreover, proper proteins replication pathogenesis. These observations indicate checkpoint virus host interaction. In this study, we summarize advances concerning regulation infection by separation. Our review highlights emerging notion robust modulator

Language: Английский

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