Ask about this productRelated genes to: PSMD2 antibody
- Gene:
- PSMD2 NIH gene
- Name:
- proteasome 26S subunit, non-ATPase 2
- Previous symbol:
- -
- Synonyms:
- S2, P97, TRAP2, MGC14274, Rpn1
- Chromosome:
- 3q27.1
- Locus Type:
- gene with protein product
- Date approved:
- 1995-11-28
- Date modifiied:
- 2016-10-05
Related products to: PSMD2 antibody
Related articles to: PSMD2 antibody
- Despite the well recognized downregulation of cytochrome P450 enzymes in metabolic dysfunction-associated steatohepatitis (MASH), the posttranscriptional mechanisms underlying this phenomenon are still not well understood. This study investigates the role of proteasomal degradation in the regulation of CYP1A2, a major hepatic P450 enzyme, during MASH progression. Using a high-fat diet-induced MASH mouse model and palmitic acid-treated hepatocytes model, we found that CYP1A2 protein levels were significantly decreased without corresponding changes in mRNA expression, indicating predominant posttranslational modification regulation. Mechanistically, we first identified 26S proteasome non-ATPase regulatory subunit 2 (PSMD2) as a novel and crucial regulatory factor that dominates the posttranslational degradation of CYP1A2 during MASH development, and confirmed it functions as a key interacting protein mediating the accelerated proteasomal degradation of CYP1A2. Inhibition of proteasome activity with bortezomib or genetic silencing of PSMD2 effectively blocked CYP1A2 degradation and ameliorated hepatocyte lipid accumulation. Importantly, hepatocyte-specific knockdown of PSMD2 in vivo restored CYP1A2 expression and significantly alleviated MASH-associated pathologies, including hepatic steatosis, inflammation, and liver injury. Collectively, these findings establish PSMD2 as a novel and essential modulator that governs the posttranslational degradation of CYP1A2. Moreover, PSMD2 plays a critical role in the progression of MASH, highlighting its potential as a therapeutic target for this disease. SIGNIFICANCE STATEMENT: This study provides the first evidence that hepatocyte proteasome non-ATPase regulatory subunit 2 (PSMD2) drives metabolic dysfunction-associated steatohepatitis pathology by promoting CYP1A2 degradation and lipid accumulation. PSMD2 deficiency alleviates hepatic steatosis, reduces triglyceride and free fatty acid levels, and restores liver function. These findings establish PSMD2 as a critical regulator of lipid metabolism and hepatocyte integrity, positioning it as a promising therapeutic target for metabolic dysfunction-associated steatohepatitis intervention. - Source: PubMed
Publication date: 2026/07/09
Liu MinLiu TianhaoLiu DongshengHe JiayingShao QinAa JiyeWang GuangjiXie Yuan - Biological age (BA) has emerged as a promising integrative indicator of physiological state and welfare, but its use within aquaculture remains underdeveloped. Previous genome-wide analysis in gilthead sea bream revealed skeletal muscle markers with inverse age-related expression and methylation patterns. Specifically, psmd2, ramp1, sirt1 and smad1 were up-regulated and hypomethylated with age, while atp1a2, bmp1, calcrl, col5a1, spred2 and thrb exhibited down-regulation coupled with hypermethylation. Here we assessed the responsiveness of this gene set across multiple aquaculture-relevant challenges using a real-time PCR array. Environmental stressors (e.g. increased temperature and high stocking density with low O concentration) induced transcriptional profiles resembling muscle gene-expression patterns of older individuals. Conversely, cold exposure and nutritional interventions, including restricted feeding and feed supplementation with bioactive protein hydrolysates, microalgae meal with a PUFA-rich lipid source, or fat emulsifiers promoted signatures aligned with those observed in younger animals. Although the direct reversal of stress-induced aging signatures was not tested, results indicate that dietary interventions elicit opposing transcriptional patterns, highlighting potential strategies to mitigate environmentally mediated aquaculture stress through targeted nutrition. These findings provide preliminary evidence of a potential relationship between BA and aquaculture stressors in farmed fish, underpinning a genomics-based framework for welfare assessment and adaptive management. - Source: PubMed
Publication date: 2026/07/09
Naya-Català FernandoGasperini AliceCarbonero-Acín BeatrizCalduch-Giner JosepBelenguer ÁlvaroPérez-Sánchez Jaume - Urinary extracellular vesicles (uEVs) are potential biomarkers for renal physiology and disease. Their isolation is challenged by Tamm-Horsfall protein (THP) contamination, particularly in high-speed ultracentrifugation (P100) fractions. Low-speed (P20) fractions contain biologically relevant uEVs, yet their proteomic composition is underexplored. This study evaluates strategies for THP removal to optimize mass spectrometry analysis and characterizes P20 and P100 uEV proteomes and its combination in healthy urine. - Source: PubMed
Publication date: 2026/06/14
Bielopolski DanaMusante LucaMolina HenrikBarrows DouglasUpson SamanthaYang LifangCarrol ThomasTobin Jonathan NKost Rhonda GErdbrügger U - The annual incidence of papillary thyroid cancer (PTC) has shown a steady increase in the number of cases. Advances in minimally invasive surgical techniques and the growing frequency of late-stage diagnoses have collectively heightened the complexity of PTC management and treatment. Tumor necrosis factor receptor-associated factor-interacting protein (TRAIP), which has been implicated in the progression of various malignancies, remains inadequately characterized in terms of its expression patterns and functional roles in papillary thyroid carcinoma. In this study, we implemented a comprehensive experimental strategy integrating tissue-based analyses, cellular functional assays, and in vivo animal models. We constructed a protein-protein interaction network and established stable cell lines with TRAIP overexpression, knockdown, knockout, and mutation. These models were subsequently analyzed using Western blotting and co-immunoprecipitation (co-IP) assays. Experimental results demonstrated significantly upregulated TRAIP expression in PTC. Silencing TRAIP markedly inhibited PTC cell proliferation and migratory potential. BRAF, a critical oncogene in PTC pathogenesis, exhibited a positive correlation with TRAIP expression both in vitro and in vivo. TRAIP was shown to regulate BRAF ubiquitination and was linked to MAPK pathway activation. However, mutation-based studies indicated that BRAF degradation did not occur via TRAIP-dependent ubiquitination. Furthermore, TRAIP was found to physically interact with both TRAF2 and BRAF, with TRAF2 displaying a higher binding affinity for TRAIP than BRAF. Overexpression of TRAIP reduced the interaction between TRAF2 and BRAF, whereas TRAF2 independently mediated BRAF ubiquitination. These findings demonstrate that TRAIP attenuates TRAF2-mediated BRAF ubiquitination, thereby promoting MAPK pathway activation in PTC cells, which subsequently enhances their proliferation and migration. - Source: PubMed
Publication date: 2026/06/12
Tang HuaxiaoChen LifangGuo ChengWei HanQi HongbingFu GuangmingDong XianningWang HonghuiWang Chengqin - Fetal brain development is crucial for lifelong neurological health, yet the impact of environmental heavy metal pollutants such as cadmium (Cd) remains incompletely understood. As a typical environmental heavy metal pollutant, Cd is widely encountered by various populations, including pregnant women, and disrupts zinc and copper ion homeostasis-processes essential for fetal brain development. However, cell-type-specific vulnerabilities underlying Cd-induced developmental neurotoxicity have been underexplored in human models. In this study, we employed cortical organoids with single-cell RNA sequencing (scRNA-seq) to evaluate the Cd-induced cell-type-specific developmental neurotoxicity and elucidate molecular mechanisms. scRNA-seq revealed that Cd exposure induced cell cycle arrest concurrent with zinc and copper ion dyshomeostasis in proliferating neural populations, inducing the loss of inhibitory neurons. Mechanistically, Cd activated ribosome biogenesis and mitochondrial energy metabolism across all cell types, while enhancing Cd detoxification in astrocytes and inducing astrocyte dysfunction. Furthermore, Cd disrupted axon guidance as evidenced by decreased axonal growth length and enhanced aberrant intercellular communication via robust binding Glu and Asp of PSMD2, TUBA1B and CFL1. Finally, MEA assays revealed that Cd exposure impaired neural network activity in cortical organoids. Our study reveals previously unrecognized mechanisms by which environmentally relevant cadmium disrupts human corticogenesis at the single-cell level, providing compelling evidence for the developmental neurotoxicity of this ubiquitous pollutant and supporting efforts to reduce prenatal Cd exposure for lifelong neurological health. - Source: PubMed
Publication date: 2026/05/22
Huang YanWang ZhiqiuLi HaoWang ZhongLuo GuimingZhao LujunZeng PingliZhu XizhiXue AiqinBian GuohuiSong DailiHe MaoyangHuang YinaGao HongZhang XinCen XiaoboBu Qian