Mechanistic Role of TRIM26 in Viral Infection and Host Defense DOI Open Access
Mona Sharma, Ke Liu, Jianchao Wei

et al.

Genes, Journal Year: 2024, Volume and Issue: 15(11), P. 1476 - 1476

Published: Nov. 15, 2024

(TRIM26) is an E3 ubiquitin ligase and a member of the TRIM family. Similar to other proteins, TRIM26 consists three domains, collectively termed RBCC: Really Interesting New Gene (RING) domain, one B-Box C terminal domain consisting PRY/SPRY domain. The exhibits relatively higher conservation compared with RING suggesting potentially similar roles across proteins from various species. either directly interacts viral or modulates immune responses engage infection, serving as protective detrimental host factor depending on circumvent infection. present review focuses understanding mechanisms during infection its potential future applications.

Language: Английский

Neutrophil-derived heparin-binding protein increases endothelial permeability in acute lung injury by promoting TRIM21 and the ubiquitination of P65 DOI Creative Commons
Jian Zhang, Yong Cao,

Wenqi Shu

et al.

Cell Biology and Toxicology, Journal Year: 2025, Volume and Issue: 41(1)

Published: March 5, 2025

Acute lung injury (ALI), which poses a significant public health threat, is commonly caused by sepsis. ALI associated with permeability and glycolysis changes in pulmonary microvascular endothelial cells. Our study demonstrates that heparin-binding protein (HBP), released from neutrophils during sepsis, exacerbates glycolysis, thereby triggering ALI. Through coimmunoprecipitation mass spectrometry, TRIM21 was identified as HBP interaction partner. Notably, enhances the stability of inhibiting K48 ubiquitination. binds to promotes K63-linked ubiquitination P65, facilitating its nuclear translocation. regulates HPMEC manner dependent on P65 stabilizes interactions P65. Rescue experiments conducted vivo vitro demonstrate modulation predominantly mediated through TRIM21-P65 axis. results suggest targeting HBP/TRIM21/P65 axis novel therapeutic strategy ameliorate

Language: Английский

Citations

1
TRIM21 restricts influenza A virus replication by ubiquitination-dependent degradation of M1 DOI Creative Commons

Lulu Lin,

Xingbo Wang, Zhen Chen

et al.

PLoS Pathogens, Journal Year: 2023, Volume and Issue: 19(6), P. e1011472 - e1011472

Published: June 21, 2023

Tripartite motif-containing protein 21 (TRIM21), an E3 ubiquitin ligase, plays a critical role in the host antiviral response. However, mechanism and spectrum of TRIM21 influenza A virus (IAV) remain unclear. Here, we report that inhibits replication various IAV subtypes by targeting matrix 1 (M1) from H3/H5/H9, but not H1 H7 M1. Mechanistically, binds to residue R95 M1 facilitates K48 ubiquitination K242 for proteasome-dependent degradation, leading inhibition H3, H5, H9 replication. Interestingly, recombinant viruses with R95K or K242R mutations were resistance exhibited more robust severe pathogenicity. Moreover, amino acid sequence proteins, mainly avian such as H5N1, H7N9, H9N2, ranging 1918 2022, reveals gradual dominant accumulation TRIM21-driven mutation when jumps into mammals. Thus, mammals' functions restriction factor drives adaptive virus.

Language: Английский

Citations

20
TRIM21 Promotes Oxidative Stress and Ferroptosis through the SQSTM1-NRF2-KEAP1 Axis to Increase the Titers of H5N1 Highly Pathogenic Avian Influenza Virus DOI Open Access
Yifan Wei,

Yongxia Gu,

Ziwei Zhou

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(6), P. 3315 - 3315

Published: March 14, 2024

Tripartite motif-containing protein 21 (TRIM21) is involved in signal transduction and antiviral responses through the ubiquitination of targets. TRIM21 was reported to be related imbalance host cell homeostasis caused by viral infection. Our studies indicated that H5N1 highly pathogenic avian influenza virus (HPAIV) infection up-regulated expression A549 cells. Western blot qPCR results showed knockdown alleviated oxidative stress ferroptosis induced HPAIV promoted activation antioxidant pathways. Co-IP regulating SQSTM1-NRF2-KEAP1 axis increasing SQSTM1 K63-linked polyubiquitination under condition In addition, attenuated inhibitory effect NAC on titers enhanced promoting agonist Erastin titers. findings provide new insight into role

Language: Английский

Citations

5
Viral infection and spread are inhibited by the polyubiquitination and downregulation of TRPV2 channel by the interferon-stimulated gene TRIM21 DOI Creative Commons

Yu‐Yao Guo,

Yue Gao,

Yunlin Zhao

et al.

Cell Reports, Journal Year: 2024, Volume and Issue: 43(4), P. 114095 - 114095

Published: April 1, 2024

Interferon (IFN) contributes to the host's antiviral response by inducing IFN-stimulated genes (ISGs). However, their functional targets and mechanism of action remain elusive. Here, we report that one such ISG, TRIM21, interacts with degrades TRPV2 channel in myeloid cells, reducing its expression providing host protection against viral infections. Moreover, infection upregulates TRIM21 paracrine autocrine manners, downregulating neighboring cells prevent spread uninfected cells. Consistently, Trim21

Language: Английский

Citations

4
The MGF300-2R Protein of African Swine Fever Virus Promotes IKKβ Ubiquitination by Recruiting the E3 Ubiquitin Ligase TRIM21 DOI Creative Commons

Zhanhao Lu,

Rui Luo,

Jing Lan

et al.

Viruses, Journal Year: 2024, Volume and Issue: 16(6), P. 949 - 949

Published: June 12, 2024

African swine fever (ASF) is an acute, hemorrhagic, highly contagious disease in pigs caused by virus (ASFV). Our previous study identified that the ASFV MGF300-2R protein functions as a virulence factor and found degrades IKK

Language: Английский

Citations

4
Comparative Analysis of HMC3 and C20 Microglial Cell Lines Reveals Differential Myeloid Characteristics and Responses to Immune Stimuli DOI Creative Commons
Bavani Gunasegaran, Shivani Krishnamurthy, Sharron Chow

et al.

Immunology, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 17, 2025

ABSTRACT Microglia are the primary resident immune cells of central nervous system (CNS) that respond to injury and infections. Being critical CNS homeostasis, microglia also have been shown contribute neurodegenerative diseases brain cancer. Hence, regarded as a potential therapeutic target in diseases, resulting an increased demand for reliable vitro models. Two human cell lines (HMC3 C20) being used multiple studies, however, knowledge their biological immunological characteristics remains limited. Our aim was identify compare changes these immortalised under normal physiological immunologically challenged conditions. Using high‐resolution quantitative mass spectrometry, we examined in‐depth proteomic profiles non‐stimulated LPS or IFN‐γ HMC3 C20 cells. findings reveal responded both treatments through upregulation immune, metabolic, antiviral pathways, while showed response associated with mitochondrial activities. Additionally, secretome analysis demonstrated release IL‐6 LPS, treatment resulted altered kynurenine pathway activity, highlighting distinct metabolic adaptations.

Language: Английский

Citations

0
TRIM21 interacts with IκBα and negatively regulates NF-κB activation in Corynebacterium pseudotuberculosis-infected macrophages DOI
Cheng-Han Wu, Xiaohan Wang, Xiaolin Li

et al.

Veterinary Immunology and Immunopathology, Journal Year: 2025, Volume and Issue: 282, P. 110910 - 110910

Published: Feb. 25, 2025

Language: Английский

Citations

0
Hypertrophic Cardiomyopathy-Associated CRYABR123W Activates Calcineurin, Reduces Calcium Sequestration, and Alters the CRYAB Interactome and the Proteomic Response to Pathological Hypertrophy DOI Open Access

Andres Thorkelsson,

Chun Chou,

Audrey Tripp

et al.

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(6), P. 2383 - 2383

Published: March 7, 2025

Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiovascular condition in world, affecting around 1 500 people. HCM characterized by ventricular wall thickening, decreased chamber volume, and diastolic dysfunction. Inherited commonly caused sarcomere gene mutations; however, approximately 50% of patients do not present with a known mutation, highlighting need for further research into additional pathological mutations. The alpha-B crystallin (CRYAB) mutation CRYABR123W was previously identified as novel sarcomere-independent causing associated NFAT signaling setting pressure overload. We generated stable H9C2 cell lines expressing FLAG-tagged wild-type mutant CRYAB, which demonstrated that increases calcineurin activity. Using AlphaFold to predict structural interaction changes, we model where uniquely binds autoinhibitory domain calcineurin. Co-immunoprecipitation using CRYAB FLAG tag followed mass spectrometry showed distinct changes protein patterns CRYABR123W. Finally, mouse heart extracts from our models without overload transverse aortic constriction (TAC) were used global proteomic phosphoproteomic analysis, dysregulation cytoskeletal, metabolomic, cardiac, immune function. Our data illustrate how drives activation exhibits cellular pathways during development cardiac hypertrophy.

Language: Английский

Citations

0
E3 ubiquitin ligases and their therapeutic potential in disease Management DOI
Geet Madhukar, Md Azizul Haque, Shawez Khan

et al.

Biochemical Pharmacology, Journal Year: 2025, Volume and Issue: unknown, P. 116875 - 116875

Published: March 1, 2025

Language: Английский

Citations

0
Ubiquitin-dependent proteasomal degradation of small hepatitis B virus surface antigen mediated by TRIM21 and antagonized by OTUD4 DOI Creative Commons

Shuxiang Wu,

Zhihan Chen,

Zhengqian Zhang

et al.

Journal of Virology, Journal Year: 2025, Volume and Issue: unknown

Published: April 25, 2025

ABSTRACT The small hepatitis B surface antigen (SHBs) is the most abundant virus (HBV) protein in individuals infected with HBV, and clearance of HBV antigen, which primarily composed SHBs, considered a surrogate biomarker for achieving functional cure chronic HBV. Understanding SHBs degradation crucial its elimination targeted eradication strategies. This study demonstrates that undergoes via ubiquitin/proteasome pathway, through K48-linked ubiquitination, K122 as critical ubiquitination site. Utilizing immunoprecipitation mass spectrometry, we identified TRIM21 (an E3 ubiquitin ligase) OTUD4 (a deubiquitinase) key regulators SHBs. We verified direct interaction between TRIM21’s coiled-coil domain, well N-terminal amino acids 1–180 OTUD4, using coimmunoprecipitation glutathione S-transferase (GST) pull-down assays both vivo vitro settings. was observed to reduce stability abundance by promoting polyubiquitination, whereas acted negate effects TRIM21-induced thereby stabilizing increasing levels Notably, TRIM21-mediated substantially impaired subviral particle virion production biological activities such migratory angiogenic capabilities, opposite effect produced introduction OTUD4. These findings suggest modulate function ubiquitination-dependent proteasomal offering new insights into clearing intervening progression HBV-related liver diseases. IMPORTANCE structural component particles infection. Gaining better understanding pathways may help inform strategies potentially support design therapies. However, specific mechanisms processes involved remain largely unexplored. reveals degraded specifically at promotes enhancing while stabilizes counteracting effects. reduces stability, production, related activities, accumulation. highlight roles regulating function, potential interventions

Language: Английский

Citations

0