Ask about this productRelated genes to: PSMD14 antibody
- Gene:
- PSMD14 NIH gene
- Name:
- proteasome 26S subunit, non-ATPase 14
- Previous symbol:
- -
- Synonyms:
- POH1, pad1, Rpn11
- Chromosome:
- 2q24.2
- Locus Type:
- gene with protein product
- Date approved:
- 2003-03-17
- Date modifiied:
- 2016-10-05
Related products to: PSMD14 antibody
Related articles to: PSMD14 antibody
- The deubiquitinase PSMD14 (also known as RPN11 or POH1), a critical component of the JAB1/MPN/Mov34 metalloenzyme family, has emerged as a pivotal regulator of protein homeostasis through its deubiquitinating activity. While preclinical studies have extensively characterized PSMD14-mediated stabilization of oncogenic substrates involved in cell cycle progression, programmed cell death, metastasis, metabolic reprogramming, and immune evasion, a translational gap remains between these mechanistic insights and clinical application. This review synthesizes current evidence demonstrating that PSMD14 drives therapeutic resistance across multiple malignancies, including resistance to cisplatin, oxaliplatin, temozolomide, anlotinib, tamoxifen, and bortezomib by deubiquitinating and stabilizing key effectors such as E2F1, ALK2, IMPDH2, estrogen receptor α, and proteasomal components. Furthermore, we highlight the prognostic value of PSMD14 as a biomarker for overall survival and recurrence prediction in hepatocellular carcinoma, pancreatic cancer, lung cancer, and other malignancies, along with its emerging role in non-tumor conditions such as glucocorticoid-induced osteoporosis and post-cardiac arrest neurological outcomes. We critically evaluate the therapeutic landscape of PSMD14 inhibitors, from natural products (thiolutin) and synthetic agents (Capzimin, O-phenanthroline) to next-generation dual-target inhibitors, and discuss the clinical barriers to translation, including off-target toxicity, patient stratification, and optimal combination strategies. By integrating mechanistic discovery with biomarker development and inhibitor optimization, this review aims to lay a foundation for the future development of PSMD14-targeted therapeutic strategies. - Source: PubMed
Publication date: 2026/09/07
Liu HongruiMa LiangWang YixuanWang YuhengChen SiyuWang MingzhenCao DinggeChen YiSi Wenzhe - Dysregulation of the ubiquitin-proteasome system contributes to hepatocellular carcinoma (HCC), but how deubiquitination is linked to transcriptional regulation and alternative splicing remains unclear. In this study, proteomic analysis identified E2F4 as a PSMD14-interacting protein. Co-immunoprecipitation and ubiquitination assays showed that PSMD14 removed K48-linked polyubiquitin chains from E2F4, thereby reducing its degradation and increasing its protein stability. Stabilized E2F4 directly bound to the PHF5A promoter and promoted PHF5A transcription. As a component of the spliceosome, PHF5A regulated alternative splicing in HCC cells, including exon 3 skipping of NASP and exon 3 inclusion of POLA1. Silencing PSMD14, E2F4, or PHF5A inhibited HCC cell proliferation, whereas re-expression of the corresponding downstream factors partially restored cell growth, supporting a functional PSMD14-E2F4-PHF5A regulatory axis. Treatment with the proteasome-associated inhibitor O-phenanthroline (OPA) reduced E2F4 and PHF5A expression, altered NASP and POLA1 splicing, and suppressed xenograft tumor growth. Moreover, overexpression of E2F4 or PHF5A partially reversed OPA-induced splicing changes and growth inhibition in vitro. These findings identify a PSMD14-E2F4-PHF5A pathway that connects protein deubiquitination with transcriptional regulation and alternative splicing, and suggest that this pathway may represent a potential therapeutic vulnerability in HCC. - Source: PubMed
Publication date: 2026/09/03
Meijuan CaiXiufeng LiYahao WangJunling ZhenQian Wang - Sepsis-associated acute respiratory distress syndrome (S-ARDS) is often followed by immunoparalysis, leaving patients vulnerable to secondary infection and adverse outcomes. Lactate is widely used as a severity marker in sepsis, but its direct contribution to immune paralysis remains unclear. We examined lactate-driven immune dysfunction in mouse models, bone marrow-derived macrophages and human CD14 monocyte-derived macrophages, and tested C646-loaded mesenchymal stromal cell-derived extracellular vesicles (EVs-C646) as an experimental intervention. Lactate elevation blunted cytokine responses after rechallenge, reduced macrophage phagocytosis, shifted macrophages toward an M2-like phenotype, expanded regulatory T cells and decreased interferon-γ (IFN-γ) responses in CD8 T cells. Mechanistically, lactate activated a p300-histone H3 lysine 18 lactylation (H3K18la) program and upregulated proteasome 26S subunit, non-ATPase 14 (PSMD14). Integrated RNA sequencing, H3K18la chromatin immunoprecipitation sequencing, public sepsis transcriptomic analysis and perturbation experiments identified PSMD14 as a lactylation-linked effector that strengthened AKT/mTOR signalling and promoted macrophage dysfunction. EVs-C646 decreased H3K18la and PSMD14 expression, restored macrophage inflammatory responsiveness, improved bacterial clearance, reduced lung injury and increased survival in experimental S-ARDS-related immunoparalysis models. These findings define a lactate-p300-H3K18la-PSMD14-AKT/mTOR pathway in immunoparalysis and support further preclinical evaluation of lactylation-targeted extracellular vesicle therapy. - Source: PubMed
Publication date: 2026/08/31
Zhang YuanyuanGuo JiaxuZhang JiaminZheng YiqunWang HaoZhang Shi - Diabetic cardiomyopathy (DbCM) is a major complication of diabetes characterized by metabolic dysregulation in the heart. This study investigated the role of the long non-coding RNA Airn in the regulation of cardiac fatty acid metabolism during DbCM. Airn expression was markedly reduced in the hearts of diabetic mice. Cardiomyocyte-specific Airn overexpression improved cardiac structure and function, enhanced fatty acid oxidation (FAO), and reduced myocardial lipid accumulation, whereas Airn knockdown induced cardiac remodeling and dysfunction even under non-diabetic conditions. Mechanistically, Airn directly interacted with the RNA-binding protein quaking (QKI) and increased QKI protein stability. The present data further support the involvement of PSMD14, a deubiquitinating enzyme, in this process. In turn, QKI bound to QKI response elements (QREs) within the 3'UTR of Pparα mRNA and promoted its stability, while Airn preserved this regulatory pathway by maintaining QKI abundance. Functionally, activation of PPARα rescued the lipotoxic phenotype induced by Airn deficiency. Together, these findings identify an Airn-QKI-PPARα signaling axis that preserves cardiac FAO and limits lipotoxic remodeling, and highlight Airn as a potential therapeutic target in DbCM. - Source: PubMed
Publication date: 2026/08/24
Peng TingweiLiu MingchuanYu ZijianWang XiaoyuZhang YanlingWang DiQi BingchaoMa WenshuaiMa FengfengSong LiqiangHu JianqiangLi Yan - The 26S proteasome is the largest known protease and an essential mediator of targeted protein degradation, a transformative therapeutic modality for human diseases. Assembly of the 26S proteasome from its 66 cognate subunits depends on nine dedicated assembly chaperones. These chaperones generally function by stabilizing fragile assembly intermediates and/or by regulating the order of subunit association. Whereas the basic functional mechanisms of eight of these nine dedicated chaperones have been at least partially elucidated, the function of Rpn14 (PAAF1 in humans) has remained fully enigmatic. Here, we use a combination of genetics, engineered crosslinking coupled with mass spectrometry, and structural modeling to reveal how Rpn14 interacts with the assembling proteasomal ATPase ring. This model refutes previous Rpn14 binding models and identifies several points of inter-protein steric clash that must undergo remodeling during proteasomal regulatory particle subcomplex maturation. We further show that Rpn14 cooperates with nucleotide to stabilize a known assembly intermediate of the proteasomal base subcomplex. Together, our results illuminate the first known function of Rpn14 during proteasome biogenesis, and provide a framework for detailed mechanistic analyses of how specific interfaces within and between proteasomal subcomplexes are remodeled during their assembly. - Source: PubMed
Publication date: 2026/08/18
Thomas QuillSterling MadisonCarnley Lauren GBetancourt DanielBlount Taylor ABitter Danielle JJiao FenglongHuang LanNemec Antonia ATomko Robert J