Ask about this productRelated genes to: SOCS3 antibody
- Gene:
- SOCS3 NIH gene
- Name:
- suppressor of cytokine signaling 3
- Previous symbol:
- -
- Synonyms:
- SSI-3, CIS3, SOCS-3, Cish3
- Chromosome:
- 17q25.3
- Locus Type:
- gene with protein product
- Date approved:
- 2002-11-13
- Date modifiied:
- 2019-04-23
Related products to: SOCS3 antibody
Related articles to: SOCS3 antibody
- Aberrant activation of the Janus kinase/Signal Transducer and Activator of Transcription (JAK/STAT) signaling pathway is associated with various pathological conditions. Suppressor of Cytokine Signaling (SOCS) proteins are able to inhibit this pathway by competitively binding to the STAT binding sites on JAK kinases (blocking the binding of STATs to JAK kinases). However, the mechanism of selective inhibition of JAK kinases by SOCSs remains poorly understood. Here, we performed microsecond-scale molecular dynamics (MD) simulations combined with molecular mechanics/generalized born surface area (MM/GBSA) binding free energy calculations, covariance analysis, and principal component analysis (PCA) to systematically compare the binding characteristics of six distinct JAK/SOCS complexes. The MM/GBSA results showed that the binding affinity of SOCS1/SOCS3 to JAK1/TYK2 is significantly stronger than that of SOCS2 to JAK1/TYK2. Correspondingly, PCA and covariance analysis revealed that SOCS2 and JAK1/TYK2 moved toward the opposite directions during the simulation. All these indicate that SOCS1/SOCS3 binds more stably to JAK1/TYK2 than SOCS2, implying that SOCS1/SOCS3 has a better inhibitory effect on JAK1/TYK2. Furthermore, the results of energy decomposition residues and hydrogen bond analysis illustrated that the strong binding ability of SOCS1/SOCS3 to JAK1/TYK2 is based on the presence of "Y", "QR", and "FF" motifs (missing in the SOCS2) in its KIR region and BC loop, which are able to form stable hydrogen bond networks and Met-aromatic interactions with the GQM motifs of JAK1/TYK2. This might be the fundamental reason why SOCS1/SOCS3 has a significantly stronger selective inhibitory effect on JAK1/TYK2 than SOCS2. Our work elucidates the dynamic structural basis of JAK/SOCS binding selectivity at the atomic level, providing new insights into the mechanism of JAK kinase selectivity and laying the foundation for the development of structure-based JAK1/TYK2-targeted cancer therapy drugs. - Source: PubMed
Publication date: 2026/04/27
Zhai XinmiaoLi YanYang Yong-BiaoLiu YeChu Huiying - Immunotherapy targeting the programmed cell death-1 (PD-1)/programmed cell death-ligand 1 (PD-L1) (PD-1/PD-L1) axis has revolutionized cancer treatment, yet its efficacy in hepatocellular carcinoma (HCC) remains limited. Emerging evidence suggests that gut microbiota plays a pivotal role in modulating tumor immune microenvironments (TIME), offering a novel avenue to enhance immunotherapy outcomes. This study investigates the regulatory effects of Lactobacillus kefiranofaciens (LK) on the TIME in HCC, focusing on its modulation of Suppressor of cytokine signaling 3 (SOCS3) expression and the Janus-activated kinase-signal transducer and activator of transcription (JAK-STAT) signaling pathway, with the goal of improving responses to anti-PD-1/PD-L1 therapy. LK was isolated from kefir grains and identified through genomic sequencing. In vitro assays, including Cell Counting Kit-8 (CCK-8), 5-Ethynyl -2'- deoxyuridine (EdU) staining, colony formation, Transwell, and apoptosis detection, were conducted using Hepa1-6 HCC cells. In vivo, subcutaneous and orthotopic HCC mouse models were treated with LK to assess tumor progression. Single-cell RNA sequencing (scRNA-seq) and Bulk RNA-seq analyses were performed to identify key signaling pathways and therapeutic targets. SOCS3 expression was manipulated via lentiviral transfection to validate its role in immunotherapy enhancement. LK significantly inhibited HCC cell growth, migration, and invasion, while promoting apoptosis in vitro. In vivo, LK treatment reduced tumor size and improved immune cell infiltration, particularly T cells and NK cells. Transcriptomic analysis revealed that LK upregulates SOCS3, suppresses the JAK-STAT signaling pathway, and reduces PD-L1 expression, enhancing T cell-mediated immune responses. This study highlights the potential of gut microbiota modulation, specifically through LK, to enhance the efficacy of anti-PD-1/PD-L1 immunotherapy in HCC by targeting SOCS3 and the JAK-STAT pathway. These findings provide a new therapeutic approach for improving immunotherapy outcomes in HCC. Gut probiotics modulate the immune microenvironment to enhance the response of liver cancer patients to anti-PD-1/PD-L1 immunotherapy: molecular mechanisms. - Source: PubMed
Publication date: 2026/04/27
Lv CaihongDu JunliFeng WanqingZhou RangChen Jie - Chronic antibody-mediated kidney rejection (CABMR) is a major cause of chronic allograft injury. Fibroblasts have been implicated in mediating this injury through activation of the IL-6 amplifier loop (IL-6 + IL-17), driven by the NF-κB and STAT3 signaling pathways. This study investigated the activation of the IL-6 amplifier loop in fibroblasts isolated from renal biopsies of patients with CABMR and evaluated the effects of IL-6 and IL-17 inhibition. Fibroblasts were cultured from 6 CABMR patient biopsy samples and treated with anti-IL-6 (100 ng/mL) and anti-IL-17 (0.75 µg/mL), both before and after stimulation with IL-6/soluble IL-6 receptor (sIL-6R) (20 ng/µL), IL-17 (50 ng/µL), or a combination. IL-6, CCL2, and CCL20 levels were measured in the culture supernatants by ELISA. The mRNA expression of IL-6, CCL2, CCL20, and SOCS3 was assessed using qPCR, and protein expression was evaluated by western blot for phosphorylated STAT3 and NF-κB p65. Synergistic activation of IL-6/sIL-6R and IL-17 significantly increased IL-6, CCL20, and MCP-1 production, whereas SOCS3 expression was downregulated. Phosphorylation of NF-κB and STAT3 was also elevated. The combined inhibition of IL-6 and IL-17 effectively reduced IL-6, MCP-1, and CCL20 levels, restored SOCS3 expression, and attenuated NF-κB and STAT3 phosphorylation. These findings highlight the role of the IL-6 amplifier loop as a potential therapeutic target in CABMR. - Source: PubMed
Singh Mantabya KumarRai Mohit KumarSingh HarshitAgarwal VikasPrasad Narayan - 2',2',4',4'-Tetrabromodiphenyl ether (BDE-47), the most widespread congener of polybrominated diphenyl ethers, has attracted considerable attention due to its environmental persistence and extensive use. Although epidemiological data associate BDE-47 exposure with increased cancer risk, its role in bladder cancer (BC) remains insufficiently characterized. We found that BDE-47 at a physiologically relevant concentration (0.1 μM, comparable to human exposure levels) enhanced malignant phenotypes of BC cells in vitro. A total of 229 candidate genes were uncovered at both bulk and single-cell transcriptomic levels through weighted gene co-expression network analysis and its single-cell extension. Functional enrichment revealed prominent involvement in inflammatory regulation, extracellular matrix remodeling, and lipid metabolism pathways, further supported by transcriptome analysis of BDE-47-treated BC cells. Protein-protein interaction network construction combined with machine learning identified eight hub genes (ACSL4, IFIH1, JAK2, PSMB9, ACSL5, SOCS3, SREBF1, and JUN) as core targets of BDE-47-driven BC progression. Molecular docking suggested favorable predicted interactions between BDE-47 and these targets. A nomogram was constructed within the TCGA-BLCA cohort to visualize the prognostic model. Collectively, our findings provide a preliminary delineation of candidate targets and pathways potentially involved in BDE-47-associated bladder cancer progression, thereby offering a rationale for further mechanistic investigations. - Source: PubMed
Publication date: 2026/04/23
Sun MinghuiHu DichaoLi TongjieChen ZepingCong BoXi ZhenWang YongchenGuo RulinZhuo JianWu WenboLiu Haitao - Chronic sleep deprivation (CSD) impairs hippocampal function and induces learning and memory deficits. Microglia-driven neuroinflammation and ferroptosis are implicated in CSD-associated hippocampal pathology, yet targeted pharmacological interventions remain limited. Here, we evaluated whether Sodium Houttuyfonate (SH) ameliorates CSD-related cognitive impairment and explored the underlying mechanisms. We used network pharmacology to predict SH targets and pathways in CSD, which were validated in CSD mice and in LPS- and Erastin-treated BV-2 microglia. Network pharmacology analysis identified multiple putative key targets shared between SH and CSD, with enrichment predominantly in inflammation-related signaling pathways. In CSD mice, SH improved cognitive performance and attenuated tissue damage in the hippocampal CA1, CA3, and DG regions. Concurrently, it suppressed hippocampal microglial activation, attenuated the inflammatory response, and alleviated CSD-induced ferroptosis-related alterations. In vitro, SH reversed LPS-induced inflammatory responses in BV-2 cells by modulating the SOCS3/STAT3 pathway, and si-SOCS3 treatment significantly diminished these anti-inflammatory effects of SH, confirming that SH's regulation of microglial inflammation is SOCS3-dependent. In an Erastin-induced ferroptosis model in BV-2 cells, SH restored the function of the classical ferroptosis regulators SLC7A11 and GPX4, as well as additional key ferroptosis-related proteins FTH1 and ACSL4, thereby ameliorating the ferroptosis phenotype. In summary, SH ameliorates CSD-associated cognitive impairment and mitigates hippocampal damage. Its mechanism may involve SOCS3/STAT3-mediated anti-inflammatory effects and regulation of multiple ferroptosis-associated proteins, including both classical regulators and additional key proteins, thereby suppressing microglia-mediated neuroinflammation and ferroptosis. This provides experimental support and new research directions for intervention strategies targeting CSD-related cognitive impairment. - Source: PubMed
Publication date: 2026/04/23
Li RunZhu YingWei HongYu MingXu Yuhao