Ask about this productRelated genes to: TRIM56 Blocking Peptide
- Gene:
- TRIM56 NIH gene
- Name:
- tripartite motif containing 56
- Previous symbol:
- -
- Synonyms:
- RNF109
- Chromosome:
- 7q22.1
- Locus Type:
- gene with protein product
- Date approved:
- 2003-01-03
- Date modifiied:
- 2016-10-05
Related products to: TRIM56 Blocking Peptide
Related articles to: TRIM56 Blocking Peptide
- The ubiquitin ligase protein tripartite-motif containing 56 (TRIM56) positively regulates Toll-like receptor-3 (TLR3) signaling by forming a complex with Toll-Interleukin-1 receptor domain-containing adapter protein inducing interferon (IFN)-beta (TRIF), independent of its E3 ligase activity. Whether TRIM56 modulates other TLR pathways in innate antiviral immunity, however, is unclear. Herein, we show ectopic expression of TRIM56 augments activation of IFN regulatory factor-3 (IRF3)-dependent promoters following stimulation by lipopolysaccharide (LPS) in HEK293-TLR4-MD2-CD14 cells while leaving activation of NF-κB-dependent promoter unaffected, suggesting TRIM56 specifically promotes immune signaling through the TLR4-TRIF axis but not the MYD88 arm downstream of this TLR. Confirming its impact on endogenous antiviral responses in immune sentinel cells naturally harboring the TLR4 pathway, we demonstrated enforced expression of TRIM56 enhanced LPS-induced expression of IFN-beta and IFN-stimulated genes (ISGs) and establishment of an antiviral state in bone marrow-derived macrophages. Importantly, depletion of endogenous TRIM56 impaired LPS-induced antiviral gene expression and cellular antiviral defense. Altogether, these data add to understanding of the role of TRIM56 in TLR-mediated innate immune responses. Given that TRIM56 is an ISG and that many immune adjuvants and some viral proteins activate TLR4, the findings of this study could have implications for designing immunotherapies, especially those against viral infections. - Source: PubMed
Publication date: 2026/07/19
Tong XiaohanLi Nan LYang DarongLiu Benjamin MLi Zhuoyuan AlexLi Kui - Influenza A virus (IAV) remains a significant public health threat due to its high variability and pathogenicity. Systematic identification of viral-host interfaces is critical for developing targeted therapies. In the present study, TurboID proximity labeling was applied to map interactomes of 10 H1N1 viral proteins in human alveolar epithelial cells A549. Key interactions were validated via co-immunoprecipitation (Co-IP), confocal microscopy, dual-luciferase reporter assays, and functional studies. Results showed that Hemagglutinin (HA) and polymerase acidic (PA) directly bound mitochondrial antiviral-signaling protein (MAVS), significantly suppressing interferon-beta (IFN-β) promoter activity and impairing phosphorylation of TANK-binding kinase 1 (TBK1)/signal transducer and activator of transcription (STAT) signaling proteins. HA exploited integrin alpha-2 (ITGA2) as a novel entry cofactor, with their interaction confirmed by bidirectional Co-IP and co-localization. ITGA2 silencing markedly reduced viral titers. Tripartite motif-containing protein 56 (TRIM56) restricted H1N1 replication by binding viral nucleoprotein (NP) and inducing proteasomal degradation via K48-linked ubiquitination. As a conclusion, this study delineates H1N1's coordinated tactics to hijack host pathways, identifying MAVS, ITGA2, and TRIM56 as pivotal nodes for combination therapies. TurboID-driven interactomics provides a promising framework for system-level antiviral discovery. - Source: PubMed
Wang MinWang ZhengLiu ChenyangDuan JiajiaWu TingFu QizhiSu Xin - Sepsis-induced acute lung injury (ALI) is a life-threatening clinical disorder with high mortality, and its pathogenesis is closely linked to excessive M1 macrophage polarization and overactivation of the STING signaling pathway. TRIM56, an E3 ubiquitin ligase, is known to participate in immune and inflammatory regulation; however, its specific role and underlying molecular mechanism in sepsis-induced ALI remain largely unclear. Here, we aimed to determine whether TRIM56 alleviates sepsis-induced ALI by inhibiting M1 macrophage polarization via promoting STING ubiquitination and proteasomal degradation. We conducted in vivo and in vitro experiments: LPS-induced ALI mouse models were established, and MH-S alveolar macrophage experiments were performed, including TRIM56 silencing, TRIM56 overexpression, and treatment with the proteasome inhibitor MG132. Lung injury was assessed using hematoxylin-eosin (HE) staining and measurement of the lung wet/dry weight ratio. The expression levels of TRIM56, STING, M1 macrophage polarization markers (F4/80 iNOS cells and CD86), and pro-inflammatory cytokines (TNF-α and IL-6) were measured by western blot, RT-qPCR, immunofluorescence, and ELISA. The interaction and ubiquitination between TRIM56 and STING were verified via immunofluorescence co-localization, co-immunoprecipitation (Co-IP), and ubiquitination assays. In sepsis-induced ALI mouse models, the proportion of M1 macrophages was significantly increased, accompanied by marked downregulation of TRIM56 and upregulation of STING in alveolar macrophages. In vitro, TRIM56 silencing significantly elevated STING protein expression (without affecting its mRNA level) and promoted M1 macrophage polarization, whereas TRIM56 overexpression reduced STING protein expression and suppressed M1 polarization. Mechanistically, TRIM56 colocalized with and directly interacted with STING in the cytoplasm, thereby promoting STING ubiquitination and proteasomal degradation-an effect abrogated by MG132 treatment. In vivo, TRIM56 overexpression significantly alleviated lung injury, reduced M1 macrophage infiltration, and inhibited pro-inflammatory cytokine secretion by downregulating STING protein. In conclusion, TRIM56 inhibits M1 macrophage polarization by promoting STING ubiquitination and proteasomal degradation, thereby mitigating sepsis-induced ALI. The TRIM56-STING axis may serve as a novel and promising therapeutic target for sepsis- induced ALI. - Source: PubMed
Publication date: 2026/05/18
Li BoLiu Yang - Non-alcoholic fatty liver disease (NAFLD) is characterized by excessive hepatic lipid accumulation and can progress to severe liver injury. Kaempferol (KPF), a plant-derived flavonoid, exhibits lipid-regulatory properties. Tripartite motif-containing protein 56 (TRIM56), an E3 ubiquitin ligase, has been reported to interact with fatty acid synthase (FASN) and limit hepatic lipogenesis. This study investigated whether KPF alleviates NAFLD through modulation of TRIM56-associated lipid metabolic pathways. Molecular docking, molecular dynamics simulations, and cellular thermal shift assays (CETSA) were employed to evaluate the interaction between KPF and TRIM56. High-fat diet-induced NAFLD mice and fatty acid-treated HepG2 cells were used to assess the effects of KPF on hepatic lipid accumulation. Histological analysis, lipid profiling, Oil Red O staining, Western blotting, immunofluorescence, and quantitative PCR were performed. Endogenous co-immunoprecipitation examined the association between TRIM56 and FASN, and siRNA-mediated knockdown of TRIM56 evaluated its functional contribution. KPF significantly reduced serum triglyceride, total cholesterol, and low-density lipoprotein cholesterol levels, ameliorated hepatic steatosis in vivo, and decreased intracellular lipid accumulation in vitro. In silico and CETSA analyses supported the engagement of TRIM56 by KPF. KPF restored TRIM56 expression under steatotic conditions, whereas TRIM56 silencing attenuated its lipid-lowering effects. TRIM56 was confirmed to associate with FASN, and KPF treatment suppressed multiple lipogenic enzymes. These findings indicate that KPF alleviates hepatic steatosis, at least in part, through modulation of TRIM56-associated lipogenic pathways, highlighting TRIM56 as a potential therapeutic target in NAFLD. - Source: PubMed
Publication date: 2026/04/23
Yang HuiWang YingruiZhu LejianChen ZhuoxiYan ShuoDu YuanWang BinshengZhang Leiming - TRIM-NHL proteins, a subfamily of Tripartite Motif (TRIM) family proteins, are characterized by the presence of NHL structures in their C-terminal domains. In humans, this subfamily mainly includes TRIM2, TRIM3, TRIM32, TRIM71, and the recently discovered TRIM56 protein. The C-terminal domains of these five proteins exhibit varying degrees of difference. Increasing evidence indicates that TRIM proteins are involved in numerous physiological and pathological processes related to life and health, and TRIM71 is no exception. In this article, we introduce the functional and structural characteristics of TRIM family proteins. We mainly discuss the known functions and related specific structures of the TRIM71 protein in the TRIM-NHL subfamily, as well as the exploration of its druggability. We also summarize and organize its physiological functions and biological processes in disease regulation. - Source: PubMed
Publication date: 2026/05/12
Gan Qi-FengHan Zi-XvZheng Zu-Guo