Ask about this productRelated genes to: USP18 antibody
- Gene:
- USP18 NIH gene
- Name:
- ubiquitin specific peptidase 18
- Previous symbol:
- -
- Synonyms:
- -
- Chromosome:
- 22q11.2
- Locus Type:
- gene with protein product
- Date approved:
- 1999-11-16
- Date modifiied:
- 2018-02-28
Related products to: USP18 antibody
Related articles to: USP18 antibody
- Viral infections in the kidney activate innate immunity double-stranded RNA (dsRNA) sensors such as retinoic acid-inducible gene-I (RIG-I). This induces the expression of interferons and interferon-stimulated genes (ISGs), including ISG15. Similarly to ubiquitin, ISG15 functions by binding to target proteins and exerting antiviral effects through ISGylation. ISG15 is secreted extracellularly and exerts antiviral effects. Ubiquitin-like modifier-activating enzyme 7 (UBA7) initiates ISGylation, whereas ubiquitin-specific protease 18 (USP18) removes ISG15 from conjugated proteins. Both RIG-I and ISG15 are involved in antiviral responses and renal fibrosis. However, their interaction during kidney inflammation remains unclear. - Source: PubMed
Tachizaki MayukiKawaguchi ShogoTanaka HiroshiImaizumi Tadaatsu - Spinocerebellar Ataxia type 2 (SCA2) and Amyotrophic Lateral Sclerosis type 13 (ALS13) are triggered by polyglutamine expansion in Ataxin-2 (ATXN2). To understand these neurodegenerative disorders at the molecular level, the brains of 10-month-old -CAG100-knockin mice were analyzed as microglial, astroglial and neuronal fractions via global RNA sequencing. Data were validated by comparison with the spinal cord oligonucleotide microarray profile or filtered by RNA-seq consistency. Here, we show that the mutation causes a massive inflammatory response in microglia and a reciprocal loss of neuronal transcripts in glial fractions, suggesting severe synapse loss. Beyond these general neurodegenerative signs, we identify pathognomonic changes in the machinery for protein translation and RNA splicing. Glial fractions showed upregulation of (to 2082%), , , , , , , , and as an unspecific neuroinflammatory signature, versus downregulation of axonal (to <19%), and synaptic , , , and mRNAs correlating with circuit disconnection. In all fractions, reductions in , , and were noted versus disease-specific inductions of ribosomal subunits, presumably mirroring the partial loss-of-function of ATXN2 as RNA translation modulator. Selective accumulations of embryonic factors and versus downregulation of adult specify the mutation impact on splicing and translation elongation. As a potential underpinning of toxic gain-of-function, the proteostasis transcript appeared increased in astroglial and microglial fractions. These transcriptome data suggest altered ribosomal and spliceosome machinery, with massive microgliosis versus mild astrogliosis, at the core of SCA2 and ALS13. - Source: PubMed
Publication date: 2026/04/15
Auburger GeorgKandi Arvind ReddyVutukuri RajkumarAlmaguer-Mederos Luis-EnriqueGispert SuzanaSen Nesli-EceKey Jana - To investigate the potential molecular regulatory mechanism of interferon-α (IFN-α)-induced disulfidptosis occurrence in human liver cancer cells. Glucose starvation and IFN-α treatment models were constructed using human hepatocellular carcinoma cell lines HepG2 and Huh7, respectively. Western blotting (WB), NADPH content measurement, and immunofluorescence staining were employed to evaluate disulfidptosis-related phenotypes, such as intracellular disulfide bond accumulation, NADPH depletion, and filamentous actin (F-actin) skeleton collapse. The reversibility of the phenotypes was validated by combining the disulfidptosis inhibitor D-penicillamine (D-Pen). The expression of solute carrier family 7 member 11 (SLC7A11) was downregulated using siRNA interference to evaluate the dependence of IFN-α-induced disulfidptosis on the SLC7A11 pathway. Furthermore, the GEO transcriptome dataset was employed to conduct differential gene analysis for screening candidate molecules involved in the regulation of IFN-α-induced disulfidptosis. Quantitative data are presented as mean ± standard deviation (SD). Comparisons between two groups were performed using the independent-samples test, while comparisons among multiple groups were analyzed by one-way analysis of variance (ANOVA), followed by Dunnett's t test for pairwise comparisons. Compared with the control group, glucose starvation and IFN-α treatment both induced disulfidptosis-related phenotypes in HepG2 and Huh7 cells, characterized by increased intracellular disulfide bond levels, decreased NADPH content, and F-actin cytoskeleton collapse. Following IFN-α treatment, the accumulation of high-molecular-weight protein aggregates increased in a time- and dose-dependent manner. Compared with IFN-α treatment alone, combined D-Pen intervention partially alleviated intracellular disulfide accumulation, NADPH depletion, and F-actin cytoskeletal collapse. Under conditions of SLC7A11 knockdown, IFN-α-induced high-molecular-weight protein aggregation was further aggravated, suggesting that regulatory mechanisms independent of SLC7A11 may also be involved in this process. Transcriptomic differential expression analysis revealed that β2-microglobulin (B2M), ubiquitin-specific peptidase 18 (USP18) and proteasome activator subunit 1 (PSME1) were upregulated following IFN-α stimulation, among which PSME1 also showed increased protein expression after IFN-α treatment. IFN-α can induce disulfidptosis-related phenotypic changes in HepG2 and Huh7 human hepatocellular carcinoma cells. The upregulation of B2M, USP18, and PSME1 suggests that these molecules may be involved in this process; however, the specific underlying mechanisms require further investigation. - Source: PubMed
Bi X YZhang JXu L HChu X RLiu S SXin Y N - Cisplatin resistance is a primary cause of treatment failure in ovarian cancer (OC), partly due to enhanced antioxidant defenses that counteract cisplatin-induced DNA damage and reactive oxygen species (ROS). Beyond the classic Glutathione Peroxidase 4 (GPX4) pathway, evidence suggests that non-canonical pathways like those mediated by Ferroptosis Suppressor Protein 1 (FSP1) may drive resistance. This study aims to elucidate how such alternative pathways facilitate resistance under cisplatin-induced ROS stress. - Source: PubMed
Publication date: 2026/04/20
Zhao ZitongGe GeGong MenghanLiu YiMa LiyingZhang DongdongSun LiSong Yongmei - Post-translational modifications (PTMs) orchestrate the dynamic functional landscape of proteins, governing cellular immunity, signaling, and stress responses. Among these modifications, ISGylation, a ubiquitin-like conjugation process driven by interferon signaling, has emerged as a pivotal regulator of antiviral defense. ISG15 (Interferon-stimulated gene 15) functions through covalent attachment of its protein product to target proteins or as a secreted immunomodulator. ISG15 plays a pivotal role in antiviral immunity and cellular stress responses via ISGylation. In this review, we present an integrative structural and evolutionary analysis of ISG15 and its conjugation/deconjugation machinery, highlighting key steps of the molecular basis of ISG15 and its function. Comparative analysis of Ubiquitin and Ubiquitin-like proteins reveals the evolutionary emergence of ISG15 as a distinct modifier. Structural modeling and visualization of ISG15 elucidates its enzymatic activation via the E1 enzyme UBA7 and its conjugation through the E2 enzyme UBCH8 and E3 ligase HERC5. Cryo-EM and modeled complexes provide detailed views of domain interactions and catalytic interfaces essential for ISG15 transfer. Furthermore, we identify flexible regions in the Ubiquitin-Fold Domains (UFD) of various E1 enzymes that may underlie substrate specificity. The interaction between ISG15 and its specific protease USP18, revealing conformational changes upon substrate binding that are likely critical for de-ISGylation. Together, our findings offer a comprehensive structural framework for understanding ISGylation, paving the way for targeted therapeutic strategies in immune modulation. - Source: PubMed
Publication date: 2026/04/14
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