Ask about this productRelated genes to: ISG15 Blocking Peptide
- Gene:
- ISG15 NIH gene
- Name:
- ISG15 ubiquitin like modifier
- Previous symbol:
- G1P2
- Synonyms:
- IFI15, UCRP
- Chromosome:
- 1p36.33
- Locus Type:
- gene with protein product
- Date approved:
- 1990-10-16
- Date modifiied:
- 2019-04-23
Related products to: ISG15 Blocking Peptide
Related articles to: ISG15 Blocking Peptide
- As a central regulator of follicular development, follicle-stimulating hormone (FSH) is widely applied to induce synchronous multi-follicular growth in assisted reproductive technologies and livestock breeding. However, the molecular mechanism linking FSH signaling to synchronous multi-follicular development remains poorly defined. This study aimed to investigate the molecular mechanism by which porcine purified pituitary FSH (pFSH) promotes translation of multiple follicles. - Source: PubMed
Publication date: 2026/08/12
Wang HuanHu ZhihuiZhu HuabinWang ChaoAn JingZhao Shanjiang - The mechanisms by which e-cigarette vaping (EV) affects lung health remain unclear. Clinical data from clusters of EV-associated lung injury indicate that EV damages distal lung parenchyma and increases vulnerability to second-hit injury, including respiratory viral infections. Using human lung endothelial and epithelial cells and precision-cut lung slices, we investigated the mechanisms underlying distal lung cell injury and repair triggered by brief (24-hour) EV exposure. Using RNA sequencing of lung tissue from Golden Syrian hamsters, we evaluated the persistence of lung stress responses (10 days after 5 days of EV exposure and determined the impact of EV on host defense against influenza A virus (IAV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections. EV disrupted the barrier function of human distal lung cells through JNK stress-response signaling, triggered autophagy with impaired autophagolysosomal degradation, suppressed mTOR signaling and cell proliferation, and culminated in apoptosis. Analysis of transcriptional responses in EV-exposed hamster lungs revealed persistent activation of pathways involving JNK signaling, autophagy, barrier dysfunction, tissue remodeling, and impaired Th1 immunity. EV pre-exposure increased the viral burden of SARS-CoV-2, downregulated antiviral genes (Ifit1, Isg15, Nfkbia), and altered Stat1 and Irf7 immune signaling, while amplifying oxidative stress and IL-12 signaling. These findings show that short-term EV exposure triggered stress-induced distal lung cell injury with persistent changes in antiviral immunity and molecular pathways associated with tissue remodeling. When sustained, as with habitual EV use, these alterations may increase susceptibility to respiratory viral infections and contribute to the development of chronic lung disease. - Source: PubMed
Publication date: 2026/08/11
Rivera Tanner CSchweitzer Kelly SCornell Christina FNall Jordan MEgersdorf NicholasMoeder CourtneyCooney Riley AVladar Eszter KGroshong Steve DDowney Gregory PBridges James PBowen RichardChu Hong WeiPetrache Irina - As an essential intracellular sensor of the RLR family, MDA5 recognizes viral dsRNA and triggers host antiviral immune responses. In this study, we cloned and characterized the MDA5 homolog from large yellow croaker (Larimichthys crocea), named Lc-MDA5. The coding sequence of Lc-MDA5 is 2,976 bp and encodes a 991 amino acids (aa) polypeptide, containing two N-terminal CARD motifs, a DEXDc, a HELICc, and a C-terminal RD domain. The gene consists of 16 exons and 15 introns. Tissue expression examination revealed widespread Lc-MDA5 expression in healthy fish, with maximal transcript levels in the liver, followed by the head kidney, gill, and spleen. Lc-MDA5 expression was strongly induced following stimulation with poly I:C, LPS, PGN, or Pseudomonas plecoglossicida. Confocal imaging showed that Lc-MDA5 exhibited cytoplasmic distribution. Co-immunoprecipitation and subcellular co-localization assays demonstrated that Lc-MDA5 interacts with either Lc-MAVS_tv1 or its transmembrane-deficient splice isoform Lc-MAVS_tv2 to form protein complexes. Overexpression of Lc-MDA5 activated the type I interferon (IFNd) promoter and upregulated IRF3 transcript levels. Moreover, SVCV replication was reduced, as indicated by decreased transcript levels of viral glycoprotein (SVCV-G) and matrix protein (SVCV-M). Co-expression of Lc-MDA5 with either Lc-MAVS_tv1 or Lc-MAVS_tv2 amplified promoter activities of IRF3, IRF7, and IFNd, elevated transcription of IRF3, IFNd, and ISG15, and suppressed SVCV-P gene expression than Lc-MDA5 alone. Overall, the present findings revealed that Lc-MDA5 contributes to host antiviral immunity by engaging MAVS and its splicing variant to activate downstream IRF3/7 and IFNd signaling cascades. - Source: PubMed
Publication date: 2026/08/10
Li YingZhang Yi FanChen Xia MingMa QiangZhang Jiao NanHuang Xiao MeiLi Jing XuanZhu Yu XuanGuo Tuan YuZou Peng Fei - The high recurrence rate of herpes simplex keratitis (HSK) is primarily attributed to the reactivation of herpes simplex virus type 1 (HSV-1) within the trigeminal ganglion (TG), a latent viral reservoir cannot be eradicated by current antiviral or anti-inflammatory therapies. This study aims to elucidate the novel immune mechanisms regulating viral reactivation within the TG and to develop a targeted therapeutic strategy based on this mechanism. We found that macrophages are the key effector cells inhibiting viral reactivation in recurrent HSK models, exerting their core antiviral function through the release of macrophage extracellular traps (METs) rather than neutrophil extracellular traps (NETs). Mechanistically, MET formation is highly dependent on the activity of peptidylarginine deiminase 2 (PAD2). Importantly, METs function not merely as physical capture structures but act as signaling vehicles by releasing osteopontin (OPN) as a key messenger. OPN activates the expression of the interferon-stimulated gene ISG15 in adjacent neurons, thereby establishing a previously unrecognized "PAD2-METs-OPN-Neuron ISG15" immune-neuron synergistic antiviral axis. To translate this mechanism into a therapeutic strategy, we engineered a lipid nanoparticle encapsulating a PAD2-overexpressing plasmid, which was further camouflaged with macrophage membranes to construct the biomimetic delivery system pPAD2@MNPs. Unlike conventional gene delivery platforms, this system leverages the "homing effect" via VLA-4/LFA-1 on the membrane surface binding to VCAM-1/ICAM-1 at inflammatory sites, this system achieves precise targeting of TG lesions. In vivo experiments confirmed that local administration of pPAD2@MNPs significantly upregulates PAD2 expression within the TG, effectively reducing viral load and improving corneal pathology scores. Furthermore, biosafety evaluations revealed no significant systemic toxicity or major organ damage induced by this nano-system. In summary, this study reveals a novel mechanism of immune-neuron crosstalk in regulating HSV-1 latency within the TG and provides a safe and effective targeted nanomedicine strategy for the radical treatment of recurrent HSK. - Source: PubMed
Publication date: 2026/08/10
Liu JunpengChu TingWan MimiXiao LiSun YiGu YunyuWang XiaoSong ZhengXie ChunlanZhang LinyanWang Jihong - Mutant C9orf72 has been extensively studied as a major genetic cause of amyotrophic lateral sclerosis and frontotemporal dementia, and is also known to generate Huntington's disease (HD)-like phenocopies. However, despite this strong disease association, the role of wild-type C9orf72 (wt-C9orf72) in neurodegeneration remains largely unexplored. HD is a neurodegenerative disease, and characterized by the accumulation of misfolded mutant Huntingtin (mHTT) and impaired proteostasis, yet the upstream mechanisms driving ubiquitin-proteasome system (UPS) dysfunction are not fully understood. Here, we identify a previously unrecognized modulatory role of wt-C9orf72 in regulating mHTT aggregation in experimental HD models. Analysis of public transcriptomic datasets reveal context-dependent C9ORF72 expression changes across HD-related human datasets, while C9orf72 levels are increased in R6/2 mouse brain lysates. Functional analyses reveal that overexpression of wt-C9orf72 increases mHTT aggregation and is accompanied by increased apoptotic signaling and reduced cell viability. Unbiased proteomic profiling identifies Stat1 as a key downstream effector. Mechanistically, wt-C9orf72 promotes Stat1 activation and nuclear translocation, leading to transcriptional upregulation of Isg15, a ubiquitin-like modifier. Elevated Isg15 disrupts UPS function, resulting in accumulation of polyubiquitinated proteins and impaired proteasomal degradation. Importantly, genetic suppression of Stat1 or Isg15 significantly attenuates C9orf72-associated mHTT aggregation, supporting a functional C9orf72-Stat1-Isg15 axis. Consistent with these cell-based findings, Stat1, phosphorylated Stat1 and Isg15 levels are elevated in the cortex and striatum of R6/2 HD mouse brains. Collectively, our findings identify a novel wt-C9orf72-Stat1-Isg15 axis that promotes proteasomal dysfunction and mHTT aggregation, providing new insights into wt-C9orf72-associated protein homeostasis. - Source: PubMed
Publication date: 2026/08/05
Chan Siew ChinTung Chih-WeiChang Chih-YiSu Ching-ChunChen Yi-ChingWu Po-MingTung Chia-YuChen Shih-FengKuo Hsiao-YingCheng Pei-HsunChen Chuan-MuYang Shang-Hsun