Ask about this productRelated genes to: PSMB10 antibody
- Gene:
- PSMB10 NIH gene
- Name:
- proteasome subunit beta 10
- Previous symbol:
- MECL1
- Synonyms:
- LMP10, MGC1665, beta2i
- Chromosome:
- 16q22.1
- Locus Type:
- gene with protein product
- Date approved:
- 1993-07-29
- Date modifiied:
- 2015-08-12
Related products to: PSMB10 antibody
Related articles to: PSMB10 antibody
- Despite significant advances, the molecular basis and thus patient-tailored therapeutic options for inborn errors of immunity remain unknown in a significant number of patients. - Source: PubMed
Publication date: 2025/11/18
Fournier BenjaminPoirier LéaAbramowski VincentMerlin EtienneDeutsch HélèneBastard PaulCallebaut IsabellePicard CapucineRosain JérémieKüry SébastienBézieau StéphaneFabre MoniqueCastelle MartinNeven BénédicteMoshous Despinade Villartay Jean-PierreEbstein Frédéric - Monoallelic variants in catalytic immunoproteasome subunits have recently been linked to proteasome-associated autoinflammatory syndromes with immunodeficiency (PRAAS-ID), yet their molecular mechanisms and clinical spectra are not fully defined. In this study, seven individuals from five unrelated families carrying five distinct monoallelic PSMB8 variants were identified. Individuals presented with neonatal-onset immunodeficiency characterized by recurrent infections, B cell lymphopenia, and hypogammaglobulinemia requiring immunoglobulin replacement. Inflammatory manifestations of variable severity included enteropathy, hepatitis, myositis, and inflammatory lung disease. Additional findings included leukocyte vacuolization in blood and bone marrow. Pathogenic variants in immunoproteasome subunits were analyzed to identify structural features associated with dominant-negative behavior. Immunoproteasome assembly and activity were investigated using complexome profiling, immunoblotting, and in-gel activity assays in proband-derived fibroblasts and transfected HEK293T cells, with downstream effects assessed by proteomic and RT-qPCR analyses. Mutant PSMB8 subunits were inefficiently incorporated into immunoproteasome complexes, leading to impaired assembly, including reduced fully assembled complexes and accumulation of assembly intermediates. This defect was accompanied by activation of the integrated stress response alongside impaired immune signaling. Monoallelic pathogenic variants in PSMB8, PSMB9, and PSMB10 associated with PRAAS-ID affected residues that are highly conserved and biophysically similar between the three immunoproteasome catalytic subunits. These shared structural features may help identify additional variants with similar disruptive effects on immunoproteasome assembly. Together, our data show that monoallelic PSMB8 variants disrupt immunoproteasome assembly, resulting in clinically variable disease with immunodeficiency and systemic inflammation. Our findings support immunoproteasome assembly disruption as a unifying dominant-negative mechanism underlying PRAAS-ID. - Source: PubMed
Publication date: 2026/05/21
Wijngaard Robinvan der Made Caspar IKalkan Uçar SemaRamakrishnan GayatriWang ManBrand JohannesRosenfeld Jill AVogel Tiphanie PNicholas Sarah KWeisz-Hubshman Monika van Karnebeek Clara D MAllenspach Eric JGardiner Taylor EPerera Kimmantudawage SumuduStark ZornitzaArmstrong Ruth KCampbell JanineVolpi StefanoDrago EnricoGattorno MarcoGrossi AliceCeccherini IsabellaCabrera-Orefice AlfredoSiebels BenteMair ThomasSchlüter HartmutSmeets Ruben Lvan Beek RonaldGoebel IngridKüchler KatrinGersting Søren WHoischen AlexanderVissers Lisenka E L MWevers Ron AMeyer-Schwesinger CatherineWortmann Saskia BOud Machteld MGuerrero-Castillo Sergio - Cutaneous melanoma (CM) is an aggressive cancer where early intervention is crucial, but the prognostic role and mechanisms of ubiquitination-related genes (URGs) in immune regulation remain unclear. This study aimed to develop a URG-based prognostic signature and explore its relationship with immune modulation in CM. We integrated single-cell RNA sequencing (scRNA-seq) and bulk RNA-seq data, identifying prognostic URGs through univariate and multivariate Cox regression. A six-gene signature (UBE2L6, SPSB1, PSMB9, PSMB10, RNF213 and ATXN3) was established and validated. The signature effectively stratified patients into high- and low-risk groups, with significant survival differences. Pathway analysis revealed immune-related processes, such as 'cytokine-cytokine receptor interaction' and 'antigen processing and presentation', enriched in the low-risk group. Immune cell infiltration analysis demonstrated significant differences in the abundance of 12 immune cell types between risk groups. Notably, PSMB9 expression was positively correlated with CD8 T cell abundance (r = 0.64, p < 0.05). scRNA-seq analysis highlighted T cells as a key cell type, with all six prognostic genes showing dynamic expression changes during T cell differentiation. Our findings suggest that URGs influence CM prognosis by modulating the immune microenvironment, offering new insights for immunotherapeutic strategies. - Source: PubMed
Publication date: 2026/04/21
Lu JianpingLin ChengGao WeiLiu JieLin YucaiChen YuXiong Jiani - Immunoproteasomes are specialized multiprotein proteases that degrade intracellular proteins. Their products serve as peptides for human leukocyte antigen class I presentation playing a key role in antiviral defense and self-tolerance. Monoallelic variants in immunoproteasome genes including proteasome subunit β type 10 have recently been associated with autoinflammatory diseases and severe combined immune deficiency. Their pathophysiological consequences remain poorly understood, and treatment options are scarce. We identified a newborn with severe T lymphopenia and a de novo dominant-negative PSMB10 p.G209R mutation after pathological T cell receptor excision circle newborn screening. We further applied molecular modeling, proteomics, transcriptomics, and ex vivo T lymphopoiesis. Simulations predicted, and biochemical studies confirmed, impaired immunoproteasome assembly and function leading to defective viral sensing and antigen presentation signatures in interferon-treated fibroblasts. Despite this, hematopoietic stem cells differentiated into T cells ex vivo, and the patient developed normal naïve T cell counts and a diverse T cell antigen receptor repertoire within the first year of life in contrast to all previously reported patients. - Source: PubMed
Publication date: 2026/04/09
Ghosh SujalWang YuqinSchultheiss ChristophBorkhardt ArndtDafun Angelique SanchezKnipp LiisaMarwitz SebastianEhl StephanSoulard ClaraHaddad ElieDey DebayanEvans GraceGolwala Zainab MBennstein Sabrina BLaws Hans-JürgenRohlfs MeinoMagg ThomasBinder MaschaKreins Alexandra YBousquet Marie-PierreMarcoux JulienKlein ChristophConn Graeme LMeiners SilkeHauck Fabian - To identify clinicopathological and molecular factors influencing immune checkpoint inhibitor efficacy in urothelial carcinoma (UC). - Source: PubMed
Publication date: 2026/01/10
Hermann-Váradi Melinda