The RING finger protein family in health and disease

Signal Transduction and Targeted Therapy, Journal Year: 2022, Volume and Issue: 7(1)

Published: Aug. 30, 2022

Ubiquitination is a highly conserved and fundamental posttranslational modification (PTM) in all eukaryotes regulating thousands of proteins. The RING (really interesting new gene) finger (RNF) protein, containing the domain, exerts E3 ubiquitin ligase that mediates covalent attachment (Ub) to target Multiple reviews have summarized critical roles tripartite-motif (TRIM) protein family, subgroup RNF proteins, various diseases, including cancer, inflammatory, infectious, neuropsychiatric disorders. Except for TRIMs, since numerous studies over past decades delineated other proteins also exert widespread involvement several their importance should not be underestimated. This review summarizes potential contribution dysregulated except pathogenesis some autoimmune neurodegenerative disorder. Since viral infection broadly involved induction development those this manuscript highlights regulatory excluding antiviral immune responses. In addition, we further discuss intervention strategies targeting prevention therapeutics human diseases.

Language: Английский

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The E3 ligase RNF5 restricts SARS-CoV-2 replication by targeting its envelope protein for degradation

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: Feb. 3, 2023

Abstract The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome 2 (SARS-CoV-2) has a global health crisis; its structural protein envelope (E) is critical for viral entry, budding, production, and induction of pathology which makes it potential target therapeutics against COVID-19. Here, we find that the E3 ligase RNF5 interacts with catalyzes ubiquitination E on 63rd lysine, leading to degradation ubiquitin-proteasome system (UPS). Importantly, RNF5-induced inhibits SARS-CoV-2 replication pharmacological activator Analog-1 alleviates development in mouse infection model. We also found distinctively expressed different age groups patients displaying severity, may be exploited as prognostic marker Furthermore, recognized from various strains SARS-CoV, suggesting targeting broad-spectrum antiviral strategy. Our findings provide novel insights into role UPS antagonizing replication, opens new avenues therapeutic intervention combat COVID-19 pandemic.

Language: Английский

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CRL4B E3 ligase recruited by PRPF19 inhibits SARS-CoV-2 infection by targeting ORF6 for ubiquitin-dependent degradation

mBio, Journal Year: 2024, Volume and Issue: 15(2)

Published: Jan. 24, 2024

The cellular biological function of the ubiquitin-proteasome pathway as an important modulator for regulation many fundamental processes has been greatly appreciated. critical role in viral pathogenesis become increasingly apparent. It is a powerful tool that host cells use to defend against infection. Some proteins can restriction factors limit infection by ubiquitin-dependent degradation. In this research, we identificated CUL4B-DDB1-PRPF19 E3 Ubiquitin Ligase Complex mediate proteasomal degradation ORF6, leading inhibition replication. Moreover, CUL4B activator etoposide alleviates disease development mouse model, suggesting agent or its derivatives may be used treat infections caused SARS-CoV-2. We believe these results will extremely useful scientific and clinic communities their search cues preventive measures combat COVID-19 pandemic.

Language: Английский

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RNF5: inhibiting antiviral immunity and shaping virus life cycle

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 14

Published: Jan. 5, 2024

RNF5 is an E3 ubiquitin ligase involved in various physiological processes such as protein localization and cancer progression. Recent studies have shown that significantly inhibits antiviral innate immunity by promoting the ubiquitination degradation of STING MAVS, which are essential adaptor proteins, well their downstream signal IRF3. The abundance delicately regulated both host factors viruses. Host been found to restrict RNF5-mediated ubiquitination, maintaining stability or MAVS through distinct mechanisms. Meanwhile, viruses developed ingenious strategies hijack ubiquitinate degrade immune proteins. Moreover, recent revealed multifaceted roles life cycle viruses, including SARS-CoV-2 KSHV. Based on these emerging discoveries, represents a novel means modulating immunity. In this review, we summarize latest research virus cycle. This comprehensive understanding could offer valuable insights into exploring potential therapeutic applications focused targeting during viral infections.

Language: Английский

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E3 ubiquitin ligase ZBTB25 suppresses beta coronavirus infection through ubiquitination of the main viral protease MPro

Journal of Biological Chemistry, Journal Year: 2023, Volume and Issue: 299(12), P. 105388 - 105388

Published: Oct. 27, 2023

The main protease of severe acute respiratory syndrome coronavirus 2, Mpro, is a key viral protein essential for infection and replication. Mpro has been the target many pharmacological efforts; however, host-specific regulation remains unclear. Here, we report ubiquitin-proteasome-dependent degradation in human cells, facilitated by E3 ubiquitin ligase ZBTB25. We demonstrate that short half-life prolonged via proteasomal inhibition, with its Lys-100 residue serving as potential acceptor. Using vitro binding assays, observed ZBTB25 bind to each other vitro, using progressive deletional mapping, further uncovered required domains this interaction. Finally, used an orthologous beta-coronavirus model genetic ablation resulted more highly infective virus, effect lost upon reconstitution deleted cells. In conclusion, these data suggest new mechanism well identify anticoronaviral ligase.

Language: Английский

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When 3D genome technology meets viral infection, including SARS‐CoV‐2

Journal of Medical Virology, Journal Year: 2022, Volume and Issue: 94(12), P. 5627 - 5639

Published: Aug. 2, 2022

Mammalian chromosomes undergo varying degrees of compression to form three-dimensional genome structures. These structures dynamic and precise chromatin interactions achieve spatial temporal regulation gene expression. Most eukaryotic DNA viruses can invade their genomes into the nucleus. However, it is still poorly understood how viral precisely positioned after entering host cell nucleus find most suitable location whether specifically interact with hijack transcriptional factories or even integrate complete its transcription replication rapidly. Chromosome conformation capture technology reveal long-range between different chromosomal sites in nucleus, potentially providing a reference for DNA-host interactions. This review summarized research progress on interaction virus impact integration regulation, aiming provide new insights laying foundation treatment infectious diseases.

Language: Английский

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Impact of TRIM5α and TRIM22 Genes Expression on the Clinical Course of Coronavirus Disease 2019

Archives of Medical Research, Journal Year: 2022, Volume and Issue: 54(2), P. 105 - 112

Published: Dec. 28, 2022

Language: Английский

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A Machine Learning Approach to Identify Potential miRNA-Gene Regulatory Network Contributing to the Pathogenesis of SARS-CoV-2 Infection

Biochemical Genetics, Journal Year: 2023, Volume and Issue: 62(2), P. 987 - 1006

Published: July 29, 2023

Language: Английский

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