Ask about this productRelated genes to: RELB Blocking Peptide
- Gene:
- RELB NIH gene
- Name:
- RELB proto-oncogene, NF-kB subunit
- Previous symbol:
- -
- Synonyms:
- REL-B
- Chromosome:
- 19q13.32
- Locus Type:
- gene with protein product
- Date approved:
- 1995-10-02
- Date modifiied:
- 2016-04-29
Related products to: RELB Blocking Peptide
Related articles to: RELB Blocking Peptide
- Ebola virus (EBOV) is among the most lethal human pathogens, yet effective treatment options remain limited. While extensive efforts have elucidated the functions of viral proteins, the temporal orchestration of host transcriptional responses-and their exploitation by EBOV during infection-remains poorly defined. Here, we performed integrated time-series transcriptomic profiling using both RNA-seq and microarray analyses to characterize dynamic host and viral gene expression. Through the combination of co-expression network construction and causal inference modeling, we reconstructed the sequential activation of viral and host genes across distinct phases of infection. Our findings show that EBOV induces only minimal transcriptional perturbations during early infection but extensively reprograms host gene expression at later stages, forming infection-specific co-expression modules enriched for antiviral signaling, immune regulation, and stress responses. To prioritize functional host factors, we integrated transcriptional modules with virus-host protein-protein interaction networks and gene-drug databases. This approach identified early-induced host genes with known or predicted interactions with EBOV proteins and pharmacologically actionable targets. RNA interference-mediated silencing of three key regulatory genes (RELB, LDLR, and MYC) significantly impaired EBOV RNA replication and progeny virus production. Furthermore, pharmacological screening identified sorafenib and thioguanine as effective inhibitors of EBOV replication, with EC₅₀ values of 1.529 μM and 2.469 μM, respectively. Collectively, our study uncovers temporally resolved host regulatory programs hijacked by EBOV and demonstrates the utility of integrating dynamic transcriptomics with systems biology, functional validation, and drug screening to identify host-targeted antivirals. These findings provide a conceptual and methodological framework for developing host-targeted therapies against highly pathogenic viruses.IMPORTANCEEbola virus is a devastating pathogen with limited treatment options. A major challenge in developing therapies is understanding how the virus dynamically hijacks our cells over time. This study provides a time-resolved map of the host transcriptional landscape during Ebola virus infection. We reveal that the virus causes minimal early changes but extensively reprograms human gene expression later, creating specific co-expression networks that are essential for viral replication. By integrating these networks with virus-host interaction data, we identified key human genes and demonstrated that silencing them impairs viral replication. Furthermore, we repurposed existing drugs, identifying sorafenib and thioguanine as effective inhibitors. Our work uncovers the temporal strategy of Ebola virus and establishes a framework for discovering host-directed therapies against this and other highly pathogenic viruses. - Source: PubMed
Publication date: 2026/04/30
Zhang NailouZheng ShaolongGao XiaoxiaoChen DanXu WenWei JinboDing QingwenLi WujianChiu SandraZheng Zhenhua - The inflammation-intestinal metaplasia (IM)-carcinoma cascade has been proposed as a framework for gastric cancer (GC) development, yet the cell-level heterogeneity and microenvironmental remodeling underlying this progression remain poorly characterized. Here, we constructed a single-cell transcriptomic atlas by integrating scRNA-seq data from chronic gastritis (superficial, CGS), IM, cancer-adjacent, and tumor tissues through a unified analytical pipeline. Seven major cell lineages were resolved. Relative to CGS, IM and GC tissues exhibited a progressive contraction of epithelial compartments accompanied by expansion of immune and stromal populations. Copy number variation (CNV) inference identified two tumor-restricted malignant epithelial subgroups-one biased toward differentiation and the other enriched for inflammatory and epithelial-mesenchymal transition (EMT) signatures-as well as putative proto-malignant intermediates that coexisted with phenotypically normal epithelium. Cell-cell communication analysis indicated broadly augmented crosstalk between epithelial cells and T cells, myeloid cells, and fibroblasts, with prominent involvement of a CD44-extracellular matrix (ECM) axis. Pseudotime trajectory analysis placed malignant epithelium at late positions along gastric and pyloric mucosal cell differentiation backbones, coinciding with increasing CNV burden and enrichment of stem-like transcriptional programs. Gene regulatory network analysis revealed coordinated activity of lineage-specification modules (HNF4/CDX, NR1H4/ESRRA), proliferative regulons (MYC/TFDP1), and inflammatory/EMT-associated programs (FOSL1/REL/NF-κB). In independent cohorts, elevated expression of several malignant-epithelium-associated transcription factors-including HNF4A, KLF3, FOSL1, TCF7L2, BCL3, RELB, ONECUT2, and MAF-correlated with unfavorable overall survival. Collectively, these findings provide single-cell-resolution evidence consistent with the proposed three-stage model of gastric carcinogenesis and highlight candidate transcriptional regulators warranting further investigation as potential early-detection biomarkers. - Source: PubMed
Publication date: 2026/04/22
Li XiulanGuo MengqiWen YunhanLong Bo - Breast cancer remains the second leading cause of cancer-related mortality among women, with triple-negative breast cancer (TNBC) exhibiting a particularly poor five-year prognosis. Here, we demonstrated that, among genetic and pharmacological perturbations targeting DNA replication, suppression of DNA polymerase epsilon (POLE) induced a potent, TNBC-specific gene expression signature enriched in inflammatory cytokines that are transcriptional targets of NF-κB. TNBC cells exhibited markedly higher levels of DNA damage and canonical NF-κB activation compared to luminal breast cancer cells. Notably, NF-κB activation in this context depended on the canonical component RELA but not the non-canonical component RELB. Mechanistically, ATM, STING, and RIG-I each contributed to NF-κB activation following POLE suppression. POLE suppression in an in vivo murine TNBC model led to cancer cell-intrinsic elimination of tumor burden and increased immune cell infiltration. Together, these findings support a model in which replication stress from POLE inhibition triggers robust NF-κB-mediated inflammation and immune microenvironment remodeling in TNBC and can independently trigger tumor eradication. These results suggest a potential therapeutic avenue for targeting POLE in TNBC. - Source: PubMed
Publication date: 2026/04/21
Sher Elizabeth FFujihara Kenji MTao AnthonySastourne-Haletou PaulErenburg DianaSviderskiy Vladislav OMir HannanKarakousi TriantafylliaLoomis Cynthia ADeng JiehuiRuggles Kelly VWong Kwok-KinPossemato Richard - Interleukin (IL)-1β is a pro-inflammatory cytokine implicated in sterile inflammation and tumor development. Investigating the role of MAPKAP kinase 2 (MK2) in IL-1β processing, we found that mRNA and IL-1β protein levels were elevated in resting -knockout (KO) macrophages and in the serum of double-KO mice. This was linked to activation of the non-canonical NF-κB pathway in the absence of MK2 or its activator, p38α. Rescue by MK2, its kinase-inactive mutant MK2K79R, or p38α suppressed this pathway and reduced expression. We also observed decreased basal protein levels of tumor suppressor p53 in - or -deficient cells. Mechanistically, p53 interacts with caspase-3, promoting cleavage of RelB, thereby inhibiting non-canonical NF-κB signaling and subsequent and expression. These findings explain elevated basal IL-1β levels in -KO macrophages and uncover a new autoregulatory mechanism of expression. Additionally, they reveal a new mechanism that contributes to the long-discussed link between cancer and inflammation, wherein the tumor suppressor p53 inhibits cytokine production in parallel. - Source: PubMed
Publication date: 2026/04/02
Herr Sarah MStalkopf DianaPadaszus SofieHerbst Lukas ADörrie AnnekeNiedenthal RainerRonkina NataliaYakovleva TatianaKotlyarov AlexeyGaestel Matthias - Although pediatric asthma is closely associated with dysregulated inflammatory cytokines, integrated analyses of inflammatory cytokine-related genes and their potential diagnostic biomarkers remain limited. - Source: PubMed
Publication date: 2026/04/07
Gao Mi MiWang XueYin LiWei Xiao YingLi Fang