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
- Sex differences in the prevalence, age of onset of symptoms, and symptom presentation have been widely described in autism spectrum disorders, yet the mechanisms underlying these sex differences remain poorly characterized. Exposing rats prenatally to valproic acid (VPA) is widely used as a model to study autism-like phenotypes. Using this model, sex-specific neuroanatomical and functional characteristics were examined in adolescent rats. We found sex differences in cortical pyramidal neuron complexity, spine density, and morphology in VPA-prenatally exposed adolescent rats. The expression of autism has been linked to various processes such as inflammation, cell signalling, endothelial function, and myelination. Sex-specific analysis of cortical gene expression showed that male VPA-prenatally exposed rats had elevated expression of genes related to neuropeptide signaling (Pdyn, Adora2a, Drd2). Female VPA-prenatally exposed rats had lower expression of genes related to vascular permeability (Angptl4, Cldn5) and inflammation (Cyr61, Usp18). Dimethyl fumarate, an activator of nuclear factor (erythroid-derived 2)-like 2 (Nrf2) and clinically approved to treat multiple sclerosis, alleviated VPA-induced behavioural alterations in object recognition, anxiety-like behaviour, and social behaviour in female VPA-exposed rats. In addition, dimethyl fumarate corrected the associated VPA-induced changes in neuronal oscillatory power and cross-frequency coupling and suppressed microglial activity, with the latter occurring selectively in female animals. Together, these findings indicate sex as an essential consideration in the development of novel pharmacotherapies for autism. Dimethyl fumarate had therapeutic properties in VPA-prenatally exposed female rats, however further studies examining its therapeutic efficacy in other models of autism are required. - Source: PubMed
Publication date: 2026/08/14
Williams Olivia O FManduca Joshua DCoulombe Alana YSmith Shannon NRock Tori MHolahan Matthew RPerreault Melissa L - Bladder cancer (BLCA) is a lethal malignancy with limited therapeutic options. The role of the transcription factor Engrailed-1 (EN1) in BLCA metabolic reprogramming was previously unknown. Our study demonstrates that EN1 is significantly overexpressed in BLCA, correlating with poor patient survival and driving tumor progression. Mechanistically, EN1 transcriptionally upregulates the deubiquitinase USP18. USP18, in turn, prevents the proteasomal degradation of ATP-citrate lyase (ACLY), thereby stabilizing this gatekeeping enzyme to enhance de novo lipogenesis. Crucially, we identified the FDA-approved drug Udenafil as a candidate EN1-targeting compound. Udenafil suppressed the USP18/ACLY axis and inhibited BLCA progression in preclinical models. This study defines the EN1-USP18-ACLY axis as a master regulator of lipogenesis and a promising therapeutic target in BLCA, supporting the repositioning of Udenafil as a potential treatment strategy. - Source: PubMed
Publication date: 2026/07/28
Zhan YingZhu ChenxiLi YangWen ChuqiLi XiangyaGuo XiaoyanHu JiaYin Zhuo - Mutations that enhance type I interferon (IFN-I) activity cause monogenic autoinflammatory disorders termed type I interferonopathies. Along with the typical neurologic and rheumatologic manifestations, severe pulmonary disease is increasingly recognized yet poorly understood. We studied three siblings presenting with early-onset, life-threatening pulmonary alveolar proteinosis (PAP) and autoinflammatory stigmata. Genetic analysis uncovered a novel homozygous variant (R223Q) in STAT2, a key mediator of IFN-I signaling, which also facilitates feedback inhibition via USP18. R223Q STAT2 preserved signal transduction and viral control in vitro. However, cells homozygous for the R223Q variant failed to terminate IFN-I responses, owing to impaired localization of USP18. Unlike in classical forms of PAP, GM-CSF signaling remained intact. Instead, persistent IFN-I signaling antagonized monocyte migration toward chemokines essential for lung trafficking. Informed by these findings, the youngest sibling received JAK inhibitor and anti-IFN-I receptor therapy with marked clinical improvement. Collectively, type I interferonopathy by mutation of STAT2 (TIMS2) compromises monocyte chemotaxis and underlies a novel mechanism of PAP. - Source: PubMed
Publication date: 2026/07/16
Gruber ConorRamba MeredithDebnath BineetaCuollo LorenzoNeehus Anna-LenaLee AngelicaButa SofijaMartin-Fernandez MartaRosain JérémieBerteloot LaurelineDrabent PhilippeLe Voyer TomSoudée CamillePeel JessicaSeeleuthner YoannPuel AnneZhang Shen-YingCiancanelli Michael JArango-Franco Carlos AMigaud MélanieFrémond Marie-LouiseRenaldo FlorenceBoespflug-Tanguy OdileDorboz ImenDubern BeatriceFonteneau TristanParvaneh NimaMolatefi RasolShahrooei MohammadDuffy DarraghBondet VincentRice Gillian ICrow Yanick JMolina Thierry JoBoddaert NathalieCasanova Jean-LaurentHoudouin VeroniqueMelki IsabelleHadchouel AliceBustamante JacintaBogunovic Dusan - Aminoglycosides remain clinically important antibiotics, but their use is limited by nephrotoxicity. Although proximal tubular accumulation mediated by megalin is well established, the downstream cellular response is still incompletely understood. Here, we compared repeated-dose transcriptomic responses to gentamicin and tobramycin in a panel of human proximal tubular models comprising primary proximal tubular epithelial cells (PTEC; three donors), human iPSC-derived proximal tubular-like cells (PTL; three donors), RPTEC/TERT1 cells, and HK-2 cells. Cells were exposed daily for seven days to 12, 250, or 450 µg/mL gentamicin or tobramycin, and gene expression was assessed using the TempO-Seq EU-ToxRisk v2.1 panel followed by DESeq2 analysis. Primary PTEC and PTL showed the clearest and most coherent response, characterised by strong induction of interferon-stimulated genes including IFI27, IFI6, IFIT1-3, ISG15, MX1, OAS1, UBE2L6, USP18, IFI44L, HERC6, and RSAD2. Targeted regulator analysis showed strong enrichment of overlapping ISGF3, IRF7, and IRF1 target networks, consistent with a dominant interferon-stimulated gene program, together with a smaller NF-κB-associated inflammatory branch. In contrast, RPTEC/TERT1 and HK-2 cells showed weaker and less coherent responses. Tobramycin generally induced a stronger and more consistent transcriptional response than gentamicin across responsive models. These data identify a robust innate immune-like transcriptional signature in human proximal tubular models following repeated aminoglycoside exposure and support primary PTEC and PTL as more informative in vitro systems for mechanistic investigation of aminoglycoside nephrotoxicity. - Source: PubMed
Publication date: 2026/07/14
Chandrasekaran VidyaMeijer TamaraLeonard Martin OWilmes AnjaJennings Paul - ISG15 represents a key ubiquitin-like modifier induced primarily by interferon signaling. ISG15 is synthesized as a precursor, processed to a mature form, and covalently conjugated to substrates through a dedicated E1-E2-E3 enzymatic cascade involving UBE1L, UBE2L6, and E3 ligases such as HERC5, TRIM25, and ARIH1. This modification is reversed by deISGylases, particularly the highly specific protease USP18, which also negatively regulates interferon signaling. ISGylation impacts diverse molecular and cellular processes, including protein stability and function, protein-protein interaction, autophagy, transcription/translation, DNA damage response, and innate immunity. Advances in chemical biology and mass spectrometry-based proteomics have enabled the characterization of enzymes involved in (de)ISGylation and mapping of ISGylated proteins and sites. Dysregulated ISGylation is implicated in cancer, infection, neurodegenerative disorders, and inflammatory diseases, underscoring its broad pathophysiological relevance. - Source: PubMed
Publication date: 2026/07/13
Shirley David JosephYoo Euna