Ask about this productRelated genes to: PSMD3 Blocking Peptide
- Gene:
- PSMD3 NIH gene
- Name:
- proteasome 26S subunit, non-ATPase 3
- Previous symbol:
- TSTA2
- Synonyms:
- S3, P58, Rpn3
- Chromosome:
- 17q21.1
- Locus Type:
- gene with protein product
- Date approved:
- 1995-11-28
- Date modifiied:
- 2016-10-05
Related products to: PSMD3 Blocking Peptide
Related articles to: PSMD3 Blocking Peptide
- The genetic architecture of idiopathic inflammatory myopathies (IIM) remains incompletely defined. When increasing sample size is not feasible, cross-trait analysis of genetically correlated diseases offer an effective strategy for discovering risk loci. Using summary statistics of IIM and B-cell lymphoma subtypes, we applied conditional false discovery rate (condFDR) and multi-trait analysis of GWAS (MTAG) to detect genetic associations with IIM risk. Single nucleotide polymorphisms (SNPs) outside the human leukocyte antigen (HLA) region meeting significance thresholds (condFDR < 0.01 or p-value < 5×10 for MTAG) were clumped and subjected to both functional annotation in FUMA and Gene Ontology (GO) biological process enrichment analysis using clusterProfiler. We identified six previously unreported loci, including three associated with dermatomyositis (12:58674304:T:C, 13:110799415:C:T, and 17:38103285:G:A) and three associated with polymyositis (PM) (4:971496:T:C, 6:396321:C:T, and 6:32650631:C:A). All non-HLA loci act as expression quantitative trait loci (eQTL) or localize within enhancer regions. Notably, these include cis-eQTLs for known IIM risk-associated genes (GSDMB, DGKQ, SLC26A1, and IDUA), as well as genes implicated in synaptic vesicle cycle (SVC) pathways, immune regulation (IKZF3, ORMDL3, IRF4, DUSP22, and SPON2), protein homeostasis (ATP23 and PSMD3), lipid metabolism (PGAP3, ORMDL3, STARD3, and DGKQ), and myopathy (COL4A1). Gene Ontology analysis revealed significant for synaptic vesicle cycle pathways in PM (FDR <0.05). These findings advance our understanding of IIM pathogenesis from a genetic perspective and highlight candidate regulatory variants for further mechanistic investigation. - Source: PubMed
Publication date: 2026/07/24
Che Weng IanJarvis James NSysojev Anton ÖbergZhu CatherinePatasova Karina Smedby Karin ELundberg Ingrid EWesterlind HelgaLamb Janine AHolmqvist Marie - Carbon dots offer excellent physico-chemical properties and biocompatibility for cancer theranostics systems, either as therapeutic agents themselves, or as potential drug carriers. It is, however, postulated that the drug carrier affects the mechanism of action and intracellular target molecules of a drug. Therefore, in the present study, we systematically evaluated protein alterations in HeLa cervical cancer cells after treatment with sulfur-doped carbon dots (S-CDs). Synchrotron Radiation μFTIR spectroscopy and label-free LC-MS/MS proteomics integrated with bioinformatics were used to assess molecular changes. μFTIR revealed a shift and increased intensity of α-helices, indicating structural changes in proteins as a result of the interaction between S-CDs and cells. Proteomic analysis identified 122 statistically significant ( ≤ 0.05) proteins with increased abundance and 61 with decreased abundance following S-CD exposure, many of which possess high α-helix content, consistent with μFTIR findings. Functional analyses showed that up-regulated proteins were enriched in molecular adaptor, transporter, and transcription regulator activities, particularly those involved in RNA metabolism and translation. Down-regulated proteins were dominated by protein-modifying enzymes and cytoskeletal components. Pathway enrichment analysis indicated alterations in mRNA processing, ribosomal pathways, translation factors, aminoacyl-tRNA biosynthesis, and proteasome degradation. Key hub proteins included ribosomal proteins and translation initiation factors. S-CD treatment led to opposite regulation of many proteins compared to their regulation in untreated HeLa cells including down-regulation of ribosomal proteins (RPS27L, RPS19, and RPS5), aminoacyl-tRNA biosynthesis proteins (IARS1, LARS1, and MARS1), and proteasome degradation proteins (PSMD2, PSMD3, and PSMD11), which aligns with the observed cytotoxic effect of S-CDs on cervical cancer cells. Overall, these results highlight significant proteomic and structural protein changes induced by S-CDs and support their potential for cervical cancer treatment, warranting further investigation of this nanomaterial's biological applications. - Source: PubMed
Publication date: 2026/03/26
Davalieva KatarinaRalić VanjaBozhinovski GjorgjiGemović BranislavaNešić Maja DKorićanac LelaDučić TanjaAlgarra ManuelPopović Iva AStepić MilutinPetković Marijana - Major depressive disorder (MDD) and inflammatory bowel disease (IBD) exhibit clinical associations, yet the cross-disease genetic links and shared mechanisms between them remain unclear. This study aims to explore the genetic associations between MDD and IBD and identify the shared risk loci, potential key tissues, and related genetic mechanisms. - Source: PubMed
Publication date: 2026/04/08
Ding YifanLuo QinghuaYan XiaojunDeng ChenweiShen PanXu YueqiZhang Leichang - Specific gut microbes are critically involved in the development of metabolic diseases, particularly obesity. Here, through analyses of diabetic patients and animal models, we identified Romboutsia ilealis as a novel gut bacterium that alleviates obesity and associated metabolic disorders by suppressing intestinal lipid absorption rather than altering energy expenditure. Metabolomic profiling revealed 2-oxoindole-3-acetate (OAA) as a key mediator of this effect, which was validated both in vitro and in vivo. Mechanistically, biotin-labeled OAA pull-down coupled with proteomics in the intestinal IPEC-J2 cells identified a direct interaction between OAA and the 26S proteasome subunit PSMD3, leading to destabilization of the mA-binding protein YTHDF2. Loss of YTHDF2 derepressed Rxrb mRNA, increasing CD36 and FABP2 expression and thereby promoting intestinal lipid absorption. Together, our findings uncover a previously unrecognized R. ilealis-OAA-PSMD3-YTHDF2-Rxrb signaling axis that links the gut microbiota to host metabolism, and highlight R. ilealis and OAA as potent next-generation probiotic or metabolite-based therapies for obesity. - Source: PubMed
Publication date: 2026/03/17
Zhu LuoyiHuang LiangLiu ShuqiLuo ShiqiLi YigeWang YizhenZong Xin - Cancer metastasis is the primary cause of cancer-related mortality, yet effective treatments remain limited. There is an urgent need to develop novel therapeutic strategies to combat metastasis. In this study, we demonstrate that the bacterial intracellular signaling molecule cyclic di-GMP (c-di-GMP, or cdG) exerts a potent inhibitory effect on cancer metastasis, particularly in metastatic breast cancer, via both in vitro and in vivo models, with little toxicity to mice. Interestingly, this antimetastatic function is achieved by suppressing the NF-κB signaling pathway, which is important for cancer progression and metastasis, but independent of STING, a previously identified c-di-GMP sensor and NF-κB regulator in mammalian cells. Surprisingly, c-di-GMP inhibits NF-κB activity (p-p65) by directly binding to the proteasome 26S subunit non-ATPase 3 (PSMD3) that we identified as a new TBK1-binding activator, and disrupting the interaction between PSMD3 and TBK1. This PSMD3-TBK1 interaction boosts the phosphorylation and activation of TBK1, representing a noncanonical function of PSMD3 distinct from its established role in proteasomal degradation. Significantly, PSMD3 is highly expressed in malignant and metastatic breast cancers, particularly triple-negative breast cancer. The compelling evidence strongly suggests PSMD3 as a promising target for developing a therapy against metastatic breast cancer. These findings underscore the high potential of c-di-GMP as a safe and effective therapeutic agent for metastatic cancers by targeting the PSMD3-TBK1-NF-κB pathway. - Source: PubMed
Publication date: 2026/02/04
Wang JieqiongMrozek AlexanderHu KewenYou HanyuTraverse Sarah ELee HyeminZeng Shelya XPang XiufengPark HeewonLu Hua