Ask about this productRelated genes to: UVRAG antibody
- Gene:
- UVRAG NIH gene
- Name:
- UV radiation resistance associated
- Previous symbol:
- -
- Synonyms:
- VPS38
- Chromosome:
- 11q13.5
- Locus Type:
- gene with protein product
- Date approved:
- 1997-01-10
- Date modifiied:
- 2016-10-05
Related products to: UVRAG antibody
Related articles to: UVRAG antibody
- RAB5-GTP activation of the multiprotein VPS34 complex II (VPS34-CII) is critical for endosomal sorting and maturation, phagocytosis, and receptor downregulation. RAB5-GTP activates VPS34-CII by binding to a helical insertion in the C2 domain of VPS34 on the BECLIN1/UVRAG-containing adaptor arm of the complex. The autophagy complex, VPS34 complex I (VPS34-CI), features a unique ATG14L subunit in place of the VPS34-CII UVRAG subunit, and we found that this distorts the adaptor arm to alter the VPS34 RAB-GTPase binding pocket so that it preferentially binds RAB1-GTP. Surprisingly, our higher-resolution single-particle cryo-EM structure of VPS34-CII showed a second RAB5-GTP binding site on the VPS15 solenoid region. This site (VPS15-RAB5-site) appears to be the primordial RAB5-binding region. A mutant in the helical insertion of the C2 domain of human VPS34 that mimics the sequence abolishes RAB5 binding to VPS34. Mutation of the VPS15-RAB5-site ortholog in VPS15 resulted in defective CPY sorting, loss of colocalisation with the RAB5 ortholog Vps21, and loss of binding to Vps21 in vitro. Evolutionary expansion from one to two RAB5-orthologue binding sites may have increased membrane binding and VPS34-CII activity to adapt to more complex endocytic systems. - Source: PubMed
Publication date: 2026/05/28
Spokaite SauleOhashi YoheiBourguet MaximeDessus Antoine NicolasWilliams Roger L - Esophageal cancer (EC) remains an extremely lethal cancer with few prognostic biomarkers and specific therapies. Although autophagy is increasingly recognized as a key force behind tumor adaptation and resistance to therapy, its systematic role at the EC progression level for prognostics, as well as for drug target prediction, remains unclear. Here, we attempted to build a systems-wide map linking autophagy- and signaling-related genes and transcriptional dysregulation, patient survival, and druggability in EC. Hub genes were found using an integrative bioinformatics pipeline based on protein-protein interaction networks and further explored using enrichment, expression, survival, and molecular docking analyses. Functional enrichment highlighted autophagy, mitophagy, ferroptosis, and immune signaling as central processes, converging with stress- and metabolism-associated pathways. Expression profile of TCGA-ESCA data demonstrated substantial overexpression of autophagy initiators and elongation factors (ATG3, ATG5, ATG7, ATG12, ATG13), upstream regulators (AMBRA1, UVRAG), and stress/metabolic mediators (TP53, MYD88, GAPDH). Kaplan-Meier analysis indicated three genes, including ATG4A, GABARAPL2, and GAPDH, that exhibited significant expression levels correlating with less survival and emphasizing their prognostic capacities. Screening for drugs also revealed AKT1, TP53, and PIK3R4 as druggable hubs, and many drugs (e.g., Everolimus, Dabrafenib, Trabectedin) showing high-affinity interactions. These findings collectively demonstrate that the progression of EC is supported by a coordinated program that integrates autophagy and metabolic reprogramming with stress and immunological signaling. The study discovers new prognostic markers (ATG4A, GABARAPL2, GAPDH) and druggable targets, which could lead to better risk stratification and smarter drug repurposing. While restricted to in silico analyses, the integrative approach provides a basis for subsequent laboratory confirmation and translational development. - Source: PubMed
Publication date: 2026/05/27
Salehi ShirinMottaghi-Dastjerdi NegarShahbazi BehzadAhmadi NahidGhorbani AbozarSoltany-Rezaee-Rad MohammadYazdani FatemeKhoshdel FarzaneNiazi Mohammad-Javad - Psychological stress impairs adult hippocampal neurogenesis (AHN) and contributes to cognitive dysfunction. Previously, we reported that chronic psychological stress or the stress hormone corticosterone (CORT) induces autophagic cell death (ACD) in adult hippocampal neural stem cells (ahNSCs). However, the regulatory mechanisms underlying this process remain largely unknown. The tumor suppressor gene is abundantly expressed in ahNSCs, yet its function under stress conditions has not been fully elucidated. Here, we demonstrate that, contrary to its well-established pro-apoptotic role, TRP53 acts as a survival factor that protects ahNSCs from stress-induced ACD. Conditional deletion of in neural stem cells heightened vulnerability to chronic restraint stress (CRS), resulting in worsened memory deficits and mood disturbances compared to wild-type controls. Mechanistically, CORT facilitated MAP1LC3/LC3-mediated autophagic degradation of TRP53 through its LC3-interacting region (LIR), thereby promoting ACD. However, overexpression of either wild-type TRP53 or a degradation-resistant LIR mutant suppressed ACD by interfering with the ATG14-containing PIK3C3/VPS34 complex. Moreover, treatment with RITA, a small-molecule activator of TRP53, disrupted the TRP53-LC3 interaction, stabilized TRP53 levels, and protected ahNSCs from ACD, ultimately preventing CRS-induced cognitive impairment in the hippocampus. These findings identify TRP53 as a key negative regulator of ACD in ahNSCs and suggest that TRP53-stabilizing small molecules could represent a novel class of antidepressant therapies by preserving AHN.: ahNSC: adult hippocampal neural stem cell; AHN: adult hippocampal neurogenesis; ACD: autophagic cell death; BafA1: bafilomycin A; ACTB actin, beta; CRS chronic restraint stress; c.CASP3: cleaved caspase 3; cKO conditional knockout; CORT: corticosterone; DG: dentate gyrus; i.p: intraperitoneal; KO: knockout; LABORAS: Laboratory Behavior Observation Registration and Analysis System; LIR LC3-interacting region; MAP1LC3/LC3: microtubule-associated protein 1 light chain 3; MDM2: MDM2 proto-oncogene; NSC: neural stem cell; PFA: paraformaldehyde; PLA: proximity ligation assay; RITA: reactivation of TRP53 and induction of tumor cell apoptosis; SGK: serum/glucocorticoid regulated kinase; SGZ: subgranular zone; STS: staurosporine; TAM: tamoxifen; TRP53: transformation related protein 53; TUNEL: terminal deoxynucleotidyl transferase dUTP nick end labeling; UVRAG: UV radiation resistance associated. - Source: PubMed
Publication date: 2026/05/28
Jung SeongheeJeong HyeonjeongChoe SeongwonChoi JieunChung Kyung MinKim Joo YeonLee EunsooLee Han-WoongJeong YoungtaeKim Eun-KyoungSun WoongYu Seong-Woon - Targeting protein-protein interaction interfaces has emerged as an effective strategy in modern anticancer drug discovery, as these interfaces regulate critical signaling pathways involved in tumor progression and survival. In this study, a structure-based strategy was used to identify potential small-molecule inhibitors targeting the interaction interface of the UVRAG-BAX protein complex. Initially, the interaction interface between UVRAG and BAX was characterized using protein-protein docking. Subsequently, virtual screening of compounds from the ZINC database was carried out, followed by molecular docking to identify molecules capable of binding to the targeted interface region. Cytotoxicity analysis using the MTT assay showed a potent inhibitory effect with an IC value of 5 ± 0.283 μM. Furthermore, mechanistic studies suggested that treatment with the compound significantly increased the intracellular level of reactive oxygen species causing apoptotic cell death, arrested the cell cycle in S phase and elevated the Sub G population in MCF-7 cells. Confocal microscopy using AO/DAPI staining further confirmed cell death in treated cells. These findings suggest that 1-[2-(4,11-dimethyl-2-oxo-6,7,8,9-tetrahydro-[1]benzofuro[3,2-]chromen-3-yl)acetyl]-4-phenylpiperidine-4-carboxylic acid (ZINC000002107582) is a promising lead compound that targets the UVRAG interaction interface and exerts potent anticancer effects in breast cancer cells. - Source: PubMed
Publication date: 2026/05/12
Kumar ShivSingh Raj BahadurDubey Vikash Kumar - Natural products are biologically active compounds used for therapeutic interventions for various diseases, particularly infections. Autophagy is an intracellular catabolic pathway involving lysosomal degradation and is closely associated with immunological pathways, effectively combating bacterial, viral, fungal, and parasitic infections. Accumulating evidence suggests that autophagy activation or inhibition by natural products promotes antimicrobial responses against various pathogens. Numerous natural products can modulate autophagy through diverse signaling pathways, suggesting their potential as a host-directed therapeutic strategy that may complement conventional drug regimens or help mitigate drug resistance in various infectious diseases. However, it remains largely unclear whether these effects are mediated by direct modulation of autophagy or indirectly through associated mechanisms, including enhanced immune defense, attenuation of pathological inflammation, or crosstalk with other organelle functions. Additionally, multiple pathogens can evade host responses; thus, autophagy activation may inadvertently create favorable conditions for certain pathogens. This review discusses the current knowledge of natural products in terms of their antimicrobial actions through autophagy regulation, particularly the roles of distinct natural product classes, such as polyphenols, alkaloids, terpenoids, quinones, peptides, and macrolides in modulating autophagy for potentially contributing to control various infectious diseases. Exploring the intricate molecular interplay between natural products and autophagy in limiting infections may provide valuable insights that could inform the development of innovative host-directed antimicrobial treatments based on autophagy regulation. 3-MA: 3-methyladenine; AM: alveolar macrophages; AMP: antimicrobial peptides; AMPK: 5' adenosine monophosphate-activated protein kinase; ARDS: acute respiratory distress syndrome; ART: artemisinin; ASFV: African swine fever virus; ATG: autophagy related; AZM: azithromycin; BafA1: bafilomycin A; BECN1: beclin 1; BMDM: bone marrow-derived macrophage; BNIP3: BCL2 interacting protein 3; BNIP3L: BCL2 interacting protein 3 like; CALCOCO2/NDP52: calcium binding and coiled-coil domain 2; CAMKK2: calcium/calmodulin-dependent protein kinase kinase 2; CBD: cannabidiol; CF: cystic fibrosis; CGA: chlorogenic acid; CGAS: cyclic GMP-AMP synthase; CHUK/IKKα: component of inhibitor of nuclear factor kappa B kinase complex; CLP: cecal ligation and puncture; CLR: clarithromycin; CMA: chaperone-mediated autophagy; CoV: coronavirus; DHT: dihydrotanshinone I; EGCG: epigallocatechin-3-gallate; EIF2A: eukaryotic translation initiation factor 2A; EIF2AK2: eukaryotic translation initiation factor 2 alpha kinase 2; ESKAPE: , and spp.; ESRRA: estrogen related receptor alpha; FOXO1: forkhead box O1; FUNDC1: FUN14 domain containing 1; HBV: hepatitis B virus; HCV: hepatitis C virus; HDT: host-directed therapy; HIV: human immunodeficiency virus; HMGB1: high mobility group box 1; HSV: herpes simplex virus; IAV: influenza A virus; ICT: isocryptotanshinone; IFN: interferon; IKBKB/IKKβ: inhibitor of nuclear factor kappa B kinase subunit beta; IL: interleukin; INH: isoniazid; IRF3: IFN regulatory factor 3; KEAP1: kelch like ECH associated protein 1; LAMP: lysosomal associated membrane protein; LAP: LC3-associated phagocytosis; LPS: lipopolysaccharide; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; MAPK: mitogen-activated protein kinase; MDM: monocyte-derived macrophage; MDR: multidrug-resistant; MON: monotropein; Mtb: ; MTOR: mechanistic target of rapamycin kinase; mtROS: mitochondrial ROS; NET: neutrophil extracellular trap; NFE2L2/Nrf2: NFE2 like bZIP transcription factor 2; NFKB/NF-κB: nuclear factor kappa B; NLRP3: NLR family pyrin domain containing 3; NLRX1: NLR family member X1; NOTCH1: notch receptor 1; NTM: nontuberculous mycobacteria; OMS: ohmyungsamycin; PAK1: p21 (RAC1) activated kinase 1; PINK1: PTEN induced kinase 1; PKM/PKM2: pyruvate kinase M1/2; PLD: phospholipase D; PM: peritoneal macrophage; PPM1A: protein phosphatase, Mg2+/Mn2+ dependent 1A; PRKN/parkin: parkin RBR E3 ubiquitin protein ligase; PtdIns3K: phosphatidylinositol 3-kinase; PtdIns3P: phosphatidylinositol-3-phosphate; PTEN: phosphatase and tensin homolog; RB1CC1/FIP200: RB1 inducible coiled-coil 1; RELA/p65: RELA proto-oncogene, NF-kB subunit; RIF: rifampicin; ROS: reactive oxygen species; RSV: resveratrol; RUBCN/rubicon: rubicon autophagy regulator; SAR: selective autophagy receptor; SIRT: sirtuin; STING1: stimulator of interferon response cGAMP interactor 1; STX17: syntaxin 17; Tat: trans-activator of transcription; TB: tuberculosis; TBK1: TANK binding kinase 1; TFEB: transcription factor EB; TLR: toll like receptor; TNA: tanshinone IIA; TNF: tumor necrosis factor; UA: ursolic acid; ULK1/Atg1: unc-51 like autophagy activating kinase 1; UPR: unfolded protein response; UVRAG: UV radiation resistance associated; VAMP8: vesicle associated membrane protein 8; VDR: vitamin D receptor; WIPI2: WD repeat domain, phosphoinositide interacting 2; ZFYVE1/DFCP1: zinc finger FYVE-type containing 1; ZIKV: Zika virus. - Source: PubMed
Publication date: 2026/04/28
Paik SeungwhaUm SoohyunKim In SooPark Eun-JinKim Kyung TaeBasu JoyotiOh Dong-ChanJo Eun-Kyeong