Ask about this productRelated genes to: USP17L2 antibody
- Gene:
- USP17L2 NIH gene
- Name:
- ubiquitin specific peptidase 17 like family member 2
- Previous symbol:
- -
- Synonyms:
- DUB3
- Chromosome:
- 8p23.1
- Locus Type:
- gene with protein product
- Date approved:
- 2009-08-12
- Date modifiied:
- 2019-02-18
Related products to: USP17L2 antibody
Related articles to: USP17L2 antibody
- The innate immune system, particularly the retinoic acid-inducible gene I (RIG-I)-like receptor (RLR) signaling pathway, is a major early defense barrier against influenza A virus infection. However, excessive immune responses can trigger lethal cytokine storms and severe immune-mediated pathology. In this study, we performed a genome-wide CRISPR/dCas9 gene activation screen in human lung epithelial (A549) cells by using an A/Puerto Rico/8/1934 (H1N1) reporter virus, and identified the ubiquitin-specific protease USP17L13 as a novel negative regulator of innate immunity that promotes influenza virus replication. Overexpression of USP17L13 significantly enhanced the replication of multiple subtypes of influenza viruses in A549 cells, including a human pandemic H1N1 virus, seasonal H3N2 viruses, as well as a globally circulating clade, 2.3.4.4b, of the highly pathogenic avian H5N1 virus. Transcriptomic analysis demonstrated that USP17L13 suppresses host antiviral defenses by downregulating nuclear factor kappa B (NF-κB) signaling and arachidonic acid metabolism, while upregulating pathways associated with ribosomal translation and oxidative phosphorylation to facilitate viral production. Mechanistically, USP17L13 attenuates the host interferon (IFN) response by promoting the degradation of the key viral RNA sensors, RIG-I, and melanoma differentiation-associated protein 5 (MDA5). Further analysis revealed that USP17L13 is inducible by type I and type II interferons as well as inflammatory cytokines, suggesting that it may act as a negative-feedback regulator to limit excessive inflammation. Collectively, our findings identify USP17L13 as a previously unrecognized proviral host factor and provide new insight into how host deubiquitinases shape influenza virus-host interactions, with potential implications for host-directed approaches to controlling excessive inflammation during viral infection and improving influenza vaccine production. - Source: PubMed
Publication date: 2026/05/20
Zhang YapingQin ChenZhuang YichaoChen LeiZeng XianyingJiang LiLi ChengjunChen HualanKong Huihui - This study explored the role of ubiquitin-specific peptidase 17-like family member 2 (USP17L2) and sphingosine kinase 1 (SphK1) in regulating macrophage autophagy and pyroptosis via the TRAF6-ULK1-NLRP3 signaling axis during Mp lipid exposure. Using in vitro and in vivo models, the study examines protein expression, cytokine levels, and cellular processes. Mechanistic explorations were performed on the mycoplasma pneumoniae pneumonia (MPP) models. Mp lipid treatment significantly upregulated SphK1 and USP17L2 expression in MH-S cells while promoting proinflammatory cytokine secretion, ROS production, and activation of pyroptosis and autophagy. Silencing SphK1 suppressed Mp lipid-induced macrophage autophagy, pyroptosis, and activation of the TRAF6-ULK1 signaling axis. Co-IP confirmed direct interaction between SphK1 and TRAF6, with SphK1 inducing ULK1 ubiquitination. USP17L2 was a specific deubiquitinating enzyme for SphK1, and the two proteins interacted. Silencing USP17L2 significantly reduced inflammatory infiltration in lung tissue, neutrophil recruitment in bronchoalveolar lavage fluid, and bacterial load in MPP mice. Concurrently, it suppressed the expression of autophagy-related molecules, pyroptosis-related molecules, and proinflammatory factors in lung tissue. In conclusion, USP17L2 stabilizes SphK1 through deubiquitination modification and activates the TRAF6-ULK1-NLRP3 signaling axis, thereby promoting macrophage autophagy and pyroptosis and exacerbating MPP damage. Silencing USP17L2 blocks this regulatory pathway, inhibiting excessive inflammatory responses and cell death. - Source: PubMed
Publication date: 2026/02/28
Liu LianhongXie JianyongWu BichenDing NiuZhang JinMeng YanniChen Yanping - Aberrant activation of the Wnt/β-catenin signaling pathway is a hallmark of colorectal cancer (CRC). Here, we identify the deubiquitinating enzyme USP17 as a critical regulator of β-catenin stability and activity in CRC. We demonstrate that USP17 directly interacts with and deubiquitinates β-catenin, preventing its degradation and enhancing its stability. CRISPR/Cas9-mediated knockdown of USP17 in CRC-derived cell lines significantly reduced β-catenin levels and suppressed epithelial-mesenchymal transition (EMT), as evidenced by distinct morphological changes and altered expression of classical EMT markers. USP17 depletion reduced the proliferation of CRC cell lines and impaired CRC tumor growth in vivo. Conversely, USP17 overexpression in immortalized rat enterocytes elevated β-catenin levels and enhanced KRAS-induced cell proliferation. RNA sequencing and quantitative proteomic analysis of USP17-depleted CRC cells revealed significant suppression of the transcriptional coactivator function of β-catenin, impacting key oncogenic-related pathways. Our findings establish USP17 as a key regulator of β-catenin signaling and highlight its potential as a candidate therapeutic target in CRC. - Source: PubMed
Publication date: 2026/02/19
Acevedo MarianaDô FlorenceEl-Mortada FirasTanguay Pierre-LucVoisin LaureHoules ThibaultLavoie GenevièveAllard DavidRoux Philippe PStagg JohnDoré SamuelWalsh LoganFourtounis JimmyBonneil EricMeloche SylvainServant Marc J - Childhood apraxia of speech (CAS) is characterized by motor discoordination in the speech domain and also in fine and gross motor systems, implicating the early developing cerebellum. Comorbidity with autism spectrum disorder (ASD) and other neurodevelopmental conditions has been observed. The genetic etiology is highly heterogeneous. Here, we present three unrelated individuals with CAS and concomitant fine and gross motor involvement but different genetic variants of interest. The DNA of the cases and their parents underwent exome sequencing and variant filtering. Using publicly available data, the genes of interest derived from the variants were investigated for expression rates in the early developing brain. Known and putative protein-protein interactions among the genes of highest confidence were identified. Of 28 variants in 28 different genes, variants with highest confidence were situated in , , , , and . High gene expression rates in the developing cerebellum were observed for and . These genes encode the α5 and β1 subunits, respectively, of the heterotrimeric extracellular laminin-511 complex, a major component of the basal membrane in many tissues. Network analysis of the five high-confidence genes required expansion with only one additional gene, , to arrive at a fully connected network. The addition of four genes and inclusion of transcriptional regulation as an additional edge type allowed connecting all 28 genes of interest to arrive at a dense connectome with 32 nodes and 73 edges, representing a network enrichment with value of < 0.001, suggesting that our network has significantly more interactions than expected under random conditions. We conclude that high levels of genetic heterogeneity converge on a functional gene network governed by stimulation of cells through laminin-511 with shared direct or regulatory expression in the developing cerebellum and phenotypic overlaps of CAS, ASD, and other neurodevelopmental disorders. - Source: PubMed
Publication date: 2026/02/13
Raaz CaitlinBruce LaurelGanapathiraju MadhaviKlein-Seetharaman JudithLiu LiDinu ValentinChapi MarjanKim EunhyoKim YookyungWhite TiffaniePeter Beate Introduction: Endometriosis is a chronic gynecological disorder characterized by the ectopic growth of endometrial-like tissue, with emerging evidence highlighting a significant genetic contribution to its etiology. While genome-wide association studies have identified multiple common variants associated with sporadic endometriosis, the contribution of rare variants in familial endometriosis remains understudied. This scoping review aims to collate the published literature on familial endometriosis and systematically curate the genetic findings reported for familial endometriosis, including details of genetic variants, gene functions, and their associated biological pathways, to explore the monogenic inheritance of this disorder. - Source: PubMed
Publication date: 2025/11/07
Joshy Liya EUppangala ShubhashreeDhyani Vijay ShreeDamerla Rama RaoMundkur AnjaliAdiga PrashanthG ShyamalaGupta Aditi