Ask about this productRelated genes to: ZNRF1 antibody
- Gene:
- ZNRF1 NIH gene
- Name:
- zinc and ring finger 1
- Previous symbol:
- -
- Synonyms:
- nin283, FLJ14846, DKFZp434E229
- Chromosome:
- 16q23.1
- Locus Type:
- gene with protein product
- Date approved:
- 2004-07-02
- Date modifiied:
- 2016-10-05
Related products to: ZNRF1 antibody
Related articles to: ZNRF1 antibody
- Fas ligand (FasL)-mediated apoptosis constrains immune responses by eliminating activated lymphocytes, yet how FasL is delivered to the plasma membrane in myeloid cells remains unclear. We identify the RING E3 ligase ZNRF1 as a macrophage-intrinsic checkpoint that licenses terminal trafficking and surface exposure of FasL. Myeloid-specific Znrf1 deletion caused age-dependent spontaneous splenomegaly and, upon allosensitization, elevated CD4/CD8 T-cell ratios, enlarged germinal centers with heightened IL-21/Tfh activity, and augmented alloantibody production. In macrophages, ZNRF1 deficiency disrupted the link between total and surface FasL. Although cellular FasL levels increased upon stimulation, there was no corresponding elevation in surface FasL, indicating a defect in terminal trafficking or docking. Confocal imaging showed preserved peripheral polarization of LAMP1⁺ lysosome-related organelles while FasL cargo did not co-accumulate at the cortex, indicating a late docking/fusion defect. Biochemically, ZNRF1 deficiency weakened the Munc18-2 (Stxbp2)-Syntaxin-3 (Stx3) interaction; Stxbp2 knockdown reduced surface FasL, and reconstitution with wild-type ZNRF1-but not the catalytically inactive C184A mutant-restored surface FasL despite similar complex assembly, establishing a requirement for ZNRF1 E3 activity. Functionally, Znrf1-deficient macrophages displayed impaired FasL-dependent killing of activated CD4⁺ T cells and Fas-sensitive targets, not rescued by stronger LPS priming. These findings define a ZNRF1-Munc18-2-Stx3 axis that couples lysosome-related organelle polarization to fusion, ensuring timely FasL availability at the macrophage surface and suggesting a tractable node to modulate immune hyperactivation. - Source: PubMed
Publication date: 2026/03/28
Lai Ting-YuChang Yung-ChiLin You-ShengTsai Ching-YiOu-Yang PuChen Chien-ChiaTsai Meng-KunHsu Li-ChungLee Chih-Yuan - Metabolic alterations and immune dysfunction within the gastric tumor microenvironment critically drive gastric cancer (GC) progression and therapeutic resistance. Although single-cell RNA sequencing (scRNA-seq) has unveiled cellular heterogeneity in GC, the metabolic landscapes of tumor cells and their interplay with immune components remain underexplored. By integrating scRNA-seq data from 35,633 cells across 23 GC tissues (GSE150290), bulk RNA-seq data from UCSC Xena, and two independent microarray cohorts (GSE26899, GSE62254), we systematically characterized metabolic heterogeneity and identified immune-related prognostic biomarkers. Reclustering of malignant epithelial cells revealed distinct metabolic phenotypes, with the citrate cycle and oxidative phosphorylation pathways emerging as key drivers of intratumoral diversity and T cell differentiation. Through machine learning and survival analyses, we discovered a novel risk score model composed of 6 T cell differentiation signatures, which stratified patients into high- and low-risk groups with significant differences in overall survival. Notably, this model outperformed traditional clinicopathological factors in predicting prognosis, validated in both bulk RNA-seq and microarray datasets. Immunohistochemistry further confirmed the prognostic value of key regulatory proteins (RGS1, CXCR4, CTLA4, ARPP19, ZNRF1, and ZNF207). Our findings highlight the metabolic immune crosstalk in GC and provide a promising biomarker panel for precision risk stratification and potential immunotherapeutic targets. - Source: PubMed
Publication date: 2026/01/01
Liu JunjunZhao RuiYao GuodongLiu ZhaoShi RunzeGeng JingshuLiang GuanyingChen Kexin - Previous studies have concluded that miRNAs may be implicated in the pathogenesis of dengue, as upregulated miRNAs were observed in blood and serum samples from infected patients. These biomarkers for dengue infection are highly promising. Among these, microRNA-21 has emerged as a major candidate, although its role in the pathogenesis of dengue infection is not clear. In this study, we predicted the target genes of miR-21 using in silico approaches and modeled guide target duplexes docked to Argonaute protein to hypothesize potential engagement with the RISC in dengue. Potential miR-21 targets and their interacting proteins were identified from public databases. Binding affinities were estimated with the help of miRWalk and miRDB, and expression across the stages of dengue was analyzed based on UniProt. Three-dimensional models of miR-21-mRNA duplexes were derived by RNA Composer and then subjected to molecular docking experiments with AGO (PDB ID: 3F73). Among them, NUDT3, MYRF, and ZNRF1 showed the highest binding affinity and were selected for molecular characterization. The mode of AGO-mediated gene silencing was further explored computationally to assess its regulatory potential. Our findings showed good agreement with previously reported interactions of miR-21 and identified new associations that may contribute to dengue pathogenesis. These genes have strong links to the progression and prognosis of disease and, hence, may serve as a potential therapeutic target. This study supports the development of RNA interference-based strategies targeting the modulation of miR-21 activity for the treatment of dengue. - Source: PubMed
Publication date: 2025/12/24
Datta DebojyatiGhosh Semanti - In livestock, copy number variations (CNVs) are important structural differences that affect phenotypic variety and adaptation. The genome-wide CNVs in 72 Red Sindhi cattle, an indigenous breed prized for its disease resistance and heat tolerance, were characterised in this study using double-digest restriction-site associated DNA sequencing (ddRAD-seq). The Illumina Novaseq platform was used to sequence the genomic DNA, and CNVs were identified using CNVnator with a 1000 bp bin size. PANTHER and Animal QTLdb were then utilized for functional annotation. A total of 3,269 high-confidence CNVs were found, mostly on autosomes. The highest number of CNVs (205) was detected on chromosome 1. Duplications mainly occurred in larger size classes (100 kb-1 Mb), while deletions were frequent in the 10-100 kb range. All regions contained 253 CNV regions (CNVRs), and 46% of individuals had a significant duplication on chromosome 18 (1-4.43 Mb). These CNVs overlapped with 2,593 genes associated with 112 quantitative trait loci (QTLs) that affected environmental adaptability, immunology, milk production, and reproduction. Znrf1, Snca, and Bola loci are important genes that have been linked to immune response and stress tolerance, underscoring their importance in the robustness of the breed. This study presents the first comprehensive CNV map for Red Sindhi cattle, highlighting the affordability of ddRAD-seq as a native breed genomic research tool. These findings support the use of marker-assisted selection and conservation techniques to produce climate-smart tropical animals. - Source: PubMed
Publication date: 2025/12/12
Nayak Sonali SonejitaMittal ShikhaVerma Surya KantDutt TriveniPanigrahi Manjit - Multiple sclerosis (MS) is an autoimmune and neuroinflammation disease characterized by axonal damage, inflammatory demyelination, and neurodegeneration. However, the precise mechanisms underlying MS pathogenesis remain largely unclear. Here, we identify ZNRF1, an E3 ubiquitin ligase, as a critical regulator of experimental autoimmune encephalomyelitis (EAE), a murine model that recapitulates the autoimmune demyelination features of MS. Mice lacking ZNRF1 exhibit increased susceptibility to EAE progression. Notably, ZNRF1 depletion in peripheral myeloid cells, but not in microglia, leads to enhanced immune cell infiltration into the central nervous system, resulting in demyelination and exacerbated disease severity. The heightened EAE severity in Znrf1-deficient mice is associated with increased polarization of Th1 and Th17 cells, elevated antigen-specific T helper cell proliferation, and amplified immune responses. Furthermore, following EAE induction, macrophages from Znrf1-deficient mice display elevated surface expression of MHC class II (MHC-II) molecules. Collectively, our findings suggest that ZNRF1 in peripheral myeloid cells plays a suppressive role in neuroinflammation by regulating MHC-II surface expression, thereby controlling antigen-specific T-cell proliferation and activation. - Source: PubMed
Publication date: 2025/10/22
Chang Yung-ChiWu Ching-ChihHsiao Fu-TingLin You-ShengLai Ting-YuHuang Kang-HsuanTang Shiue-ChengLee Chih-YuanChou Shen-JuHsu Li-Chung