A Systematic Compilation of Human SH3 Domains: A Versatile Superfamily in Cellular Signaling

Cells, Journal Year: 2023, Volume and Issue: 12(16), P. 2054 - 2054

Published: Aug. 12, 2023

SRC homology 3 (SH3) domains are fundamental modules that enable the assembly of protein complexes through physical interactions with a pool proline-rich/noncanonical motifs from partner proteins. They widely studied modular building blocks across all five kingdoms life and viruses, mediating various biological processes. The SH3 also implicated in development human diseases, such as cancer, leukemia, osteoporosis, Alzheimer’s disease, infections. A database search proteome reveals existence 298 221 domain-containing proteins (SH3DCPs), ranging 13 to 720 kilodaltons. phylogenetic analysis SH3DCPs based on their multi-domain architecture seems be most practical way classify them functionally, regard physiological pathways. This review further summarizes achievements made classification domain functions, binding specificity, significance for diseases when exploiting drug targets.

Language: Английский

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Exploring the theranostic potentials of miRNA and epigenetic networks in autoimmune diseases: A comprehensive review

Immunity Inflammation and Disease, Journal Year: 2023, Volume and Issue: 11(12)

Published: Dec. 1, 2023

Abstract Background Autoimmune diseases (AD) are severe pathophysiological ailments that stimulated by an exaggerated immunogenic response towards self‐antigens, which can cause systemic or site‐specific organ damage. An array of complex genetic and epigenetic facets majorly contributes to the progression AD, thus providing significant insight into regulatory mechanism microRNA (miRNA). miRNAs short, non‐coding RNAs have been identified as essential contributors post‐transcriptional regulation host genome expression crucial regulators a myriad biological processes such immune homeostasis, T helper cell differentiation, central peripheral tolerance, development. Aims This article tends deliberate conceptualize brief pathogenesis pertinent well miRNA networks affecting five different ADs namely rheumatoid arthritis (RA), type 1 diabetes, multiple sclerosis (MS), lupus erythematosus (SLE) inflammatory bowel disorder (IBD) thereby novel miRNA‐based theranostic interventions. Results & Discussion Pertaining differential attributed in target tissues cellular bodies innate adaptive immunity, paradigm scientific expeditions suggests optimistic correlation between dysfunction alterations. Conclusion Therefore, it is not astonishing dysregulations patterns now recognized wide spectrum disorders, establishing themselves potential biomarkers therapeutic targets. Owing its potencies, targets widely utilized development biosensors other molecules originating from same.

Language: Английский

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Critical roles of IL-6 signaling in myoblast differentiation of human adipose-derived mesenchymal stem cells

Inflammation and Regeneration, Journal Year: 2025, Volume and Issue: 45(1)

Published: April 10, 2025

Abstract Background Ectopic fat is also formed in muscles as well the liver, where adipose-derived mesenchymal stem cells (ADSCs) promote adipogenesis. On other hand, after muscle injury, satellite (SCs) contribute to repair through myodifferentiation. Human ADSCs are multipotent cells, but it remains unclear whether they involved myoblast differentiation. The aim find a novel myogenic cytokine and its signaling pathway that promotes differentiation of human ADSCs—a potential source new precursor cells—into myoblasts. Methods An array kit was used detect cytokines produced by ADSCs. After treating with DNA methyltransferase inhibitor 5-Aza-2’-deoxycytidine (5-aza-C) different JAK inhibitors, MyHC1, myodifferentiation marker, detected immunofluorescence staining reverse transcription‐quantitative polymerase chain reaction (RT-qPCR). expression status molecules determined Western blotting recruitment transcription factors MYOG promoter chromatin immunoprecipitation (ChIP). Results IL-6 at high concentrations culture supernatant stimulated 5-aza-C became strongly positive for MyHC1 on day 21 post-stimulation. When co-stimulated IL-6/sIL-6R, protein upregulated mRNA early 14 Co-stimulation IL-6/sIL-6R resulted phosphorylation STAT1 STAT3. addition JAK2 inhibitor, not JAK1/3 abolished positivity during myogenesis process STAT1, STAT3, promoter. Myoblast induced stimulation enhanced activation IL-6/JAK2/STAT1/MYOG pathway. Conclusions Therefore, sustained IL-6/JAK2/STAT1 may serve an important driver ADSC into myoblast, suggesting candidate ameliorating atrophy.

Language: Английский

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The Ubiquitin-Associated and SH3 Domain-Containing Proteins (UBASH3) Family in Mammalian Development and Immune Response

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(3), P. 1932 - 1932

Published: Feb. 5, 2024

UBASH3A and UBASH3B are protein families of atypical tyrosine phosphatases that function as regulators various cellular processes during mammalian development. As has only mild phosphatase activity, its regulatory effects based on the phosphatase-independent mechanisms. On contrary, strong suppression receptor signalling is mediated by Syk Zap-70 kinases. The functions particularly evident in lymphoid tissues kidney These also known to play key roles autoimmunity neoplasms. However, their involvement development largely unknown discussed this review.

Language: Английский

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Pathogenic role of super-enhancers as potential therapeutic targets in lung cancer

Frontiers in Pharmacology, Journal Year: 2024, Volume and Issue: 15

Published: April 12, 2024

Lung cancer is still one of the deadliest malignancies today, and most patients with advanced lung pass away from disease progression that uncontrollable by medications. Super-enhancers (SEs) are large clusters enhancers in genome’s non-coding sequences actively trigger transcription. Although SEs have just been identified over past 10 years, their intricate structure crucial role determining cell identity promoting tumorigenesis increasingly coming to light. Here, we review structural composition SEs, auto-regulatory circuits, control mechanisms downstream genes pathways, characterization subgroups classified according cancer. Additionally, discuss therapeutic targets, several small-molecule inhibitors, available treatment options for Combination therapies demonstrated considerable advantages preclinical models, anticipate these drugs will soon enter clinical studies benefit patients.

Language: Английский

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Integrative Multiomics Network Analysis of Genetic Risk Factors to Infer Biomarkers and Therapeutic Targets for Rheumatoid Arthritis

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: Jan. 5, 2024

Abstract Purpose : Understanding the interplay between multiomics genetic risk factors in rheumatoid arthritis (RA) is key to developing effective treatments. Although network genetic-medicine approaches have identified regulatory nodes of RA, there has been limited analysis molecular interactions its actors. Methods To identify significant pathways and predict therapeutic targets we implemented a workflow enable computational associated using disease mapping function similarities. Results We 28 common biomarkers three main biological pathways. Two proteins are discovered as potential RA drug causal factor with Alzheimer’s disease. Conclusion This suggests that drugs approved for other diseases mapped could be repurposed same study provides insight into pathogenesis enhances discovery complex multifactorial diseases.

Language: Английский

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Identification of New Single Nucleotide Polymorphisms Potentially Related to Small Ruminant Lentivirus Infection Susceptibility in Goats Based on Data Selected from High-Throughput Sequencing

Pathogens, Journal Year: 2024, Volume and Issue: 13(10), P. 830 - 830

Published: Sept. 25, 2024

Small ruminant lentivirus (SRLV) infections are spread in the flocks of sheep and goats all over world, causing economic loss. Although only a fraction infected animals develop disease symptoms, them may shed virus, uncontrolled infection. Antibodies against virus can be detected blood main marker Additionally, most animals, proviral DNA also detected, but at different levels. Due to lack treatment or vaccines, effective strategy prevent SRLV control programmes introduced by several countries based on elimination seropositive individuals from flock. An alternative approach, which has currently become rationale, is an identification host factors predispose certain breeds resistance susceptibility small In our work, attention was paid Carpathian breed with SRLV. Available RNA-seq results 12 determined level load were used analyse single nucleotide polymorphisms (SNPs) variant calling method. Six SNPs within five genes (POU2AF1, BCAT2, TMEM154, PARP14, UBASH3A) selected for genotyping determine their association group 60 goats. Interestingly, seronegative individuals, TT genotype PARP14 gene observed, while TMEM154 CC found Both considered potential markers resistance/susceptibility contrast, identified POU2AF1 UBASH3A seemed deleterious respective protein functions; therefore, these less likely recognised as

Language: Английский

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Roles of TULA-family proteins in T cells and autoimmune diseases

Genes and Immunity, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 18, 2024

Language: Английский

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Critical roles of IL-6 signaling in myogenesis of human adipose-derived mesenchymal stem cells

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 17, 2024

Background: Sarcopenia is a progressive skeletal muscle disease that most common in older adults. With no specific pharmacological therapies for sarcopenia, the development of specifically focus on regeneration an urgent issue. Aim to find novel myogenic cytokine and its signaling pathway promotes differentiation human adipose-derived mesenchymal stem cells (ADSCs) – potential source new precursor into myoblasts. Methods: An array kit was used detect cytokines produced by ADSCs. After treating ADSCs with DNA methyltransferase inhibitor 5-Aza-2’-deoxycytidine (5-aza-C) different JAK inhibitors, MyHC1, myodifferentiation marker, detected immunofluorescence staining reverse transcription‐quantitative polymerase chain reaction (RT-qPCR). The expression status molecules determined Western blotting recruitment transcription factors MYOG promoter chromatin immunoprecipitation (ChIP). Results: IL-6 at high concentrations culture supernatant stimulated 5-aza-C became strongly positive MyHC1 day 21 post-stimulation. When co-stimulated IL-6/sIL-6R, expressed MYOG as early 14 Co-stimulation IL-6/sIL-6R resulted phosphorylation STAT1 STAT3. addition JAK2 inhibitor, but not JAK1/3 abolished positivity during myogenesis process STAT1, STAT3, promoter. Myoblast induced stimulation enhanced activation IL-6/JAK2/STAT1/MYOG pathway. Conclusions: Therefore, sustained IL-6/JAK2/STAT1 may serve important driver regeneration, providing therapeutic basis addressing sarcopenia.

Language: Английский

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Correction: IL-6 production through repression of UBASH3A gene via epigenetic dysregulation of super-enhancer in CD4+ T cells in rheumatoid arthritis

Inflammation and Regeneration, Journal Year: 2022, Volume and Issue: 42(1)

Published: Dec. 2, 2022

Language: Английский

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