Proteins USP14 , Human
- Known as:
- Proteins USP14 , Human
- Catalog number:
- C191
- Product Quantity:
- 10μg
- Category:
- -
- Supplier:
- Novoprotein
- Gene target:
- Proteins USP14 Human
Related genes to: Proteins USP14 , Human
- Gene:
- USP14 NIH gene
- Name:
- ubiquitin specific peptidase 14
- Previous symbol:
- -
- Synonyms:
- TGT
- Chromosome:
- 18p11.32
- Locus Type:
- gene with protein product
- Date approved:
- 1999-02-01
- Date modifiied:
- 2016-02-23
Related products to: Proteins USP14 , Human
Related articles to: Proteins USP14 , Human
- Myocardial ischemia/reperfusion (MI/R) injury remains a major clinical challenge characterized by inflammation and progressive cardiomyocyte loss. Although pyroptosis is known to drive this pathogenesis, the upstream molecular switches that trigger the pyroptotic cascade remain poorly understood. Here, we investigated the role of Keratin 19 (KRT19) and its regulation by the deubiquitinase USP14 in MI/R-induced pyroptosis. - Source: PubMed
Publication date: 2026/09/27
Niu XiaoweiLei PengShuai TiankuiZhang BoWei ShihanBai Ming - Septic cardiomyopathy is driven by immunoinflammatory activation, oxidative stress, and mitochondrial quality-control failure. However, whether pharmacological targeting of USP14 can attenuate septic myocardial injury through Bach1/Nrf2-associated inflammatory and mitochondrial responses remains unclear. - Source: PubMed
Publication date: 2026/09/27
Huang MingLiu JunChen Yu HanJiang Bang YanTian HaoHuang HongQiao Hong Yan - Radiotherapy is one of the most effective treatments for glioma, but therapeutic efficacy is strongly limited due to intrinsic radioresistance, which is closely linked to reactive oxygen species. This research was designed to elucidate the role and underlying mechanisms of the deubiquitinase ubiquitin-specific protease 14 (USP14) in reactive oxygen species Accumulation and radioresistance of glioma. Bioinformatics analysis demonstrated that upregulation of USP14 was associated with tumor progression, high levels of USP14 in glioma patients were correlated with a significantly poorer prognosis. Cytological experimental results demonstrated that radiotherapy could induce increased USP14 expression. Inhibition of USP14 disrupted intracellular protein homeostasis, leading to upregulation of endoplasmic reticulum stress-related proteins thereby exacerbating endoplasmic reticulum stress. This stress response further induced substantial reactive oxygen species generation and DNA damage accumulation, ultimately synergistically enhancing the tumoricidal effect of radiotherapy. In vivo, the combined application of b-AP15 (a USP14 inhibitor) and radiotherapy elicited potent antitumor effects, marked by significant suppression of tumor growth and increased apoptotic cell death. In summary, we reveal a new regulatory axis by which USP14 governs glioma radiosensitivity through reactive oxygen species-mediated DNA damage and apoptosis, providing a promising therapeutic target and strategy for reversing clinical radioresistance. - Source: PubMed
Publication date: 2026/09/12
Liu XinyuShen LichenLu YijunWang ZimengYuan ShuanghuGu HongcangQian Junchao - Glioblastoma multiforme (GBM) is the most aggressive primary brain tumor, for which radiotherapy constitutes the key component of standard comprehensive treatment; however, tumor relapse could inevitably arise from intrinsically radioresistant GBM subclones. Radiotherapy exerts biphasic regulatory effects on the tumor immune microenvironment (TIME), with transient activation followed by sustained immunosuppression. Nevertheless, it remains elusive how radioresistant GBM cells remodel such an immunosuppressive TIME to evade immune surveillance. Herein, integrative analyses encompassing clinical specimens, public single-cell RNA-seq datasets, orthotopic glioma models, primary CD8 T cell co-culture systems, and tandem mass tag (TMT) proteomics indicated that CD81 was highly expressed in radioresistant GBM and governed GBM immune evasion. CD81-high tumor cells were surrounded by functionally exhausted CD8 T cells, alongside immunosuppressive signature within neighboring myeloid and NK cells. CD81 depletion promoted selective macroautophagic/autophagic degradation of CD274/PD-L1, increased CD8 T cell infiltration and cytotoxic activity, reduced M2-like tumor-associated macrophages, and suppressed intracranial tumor growth. Moreover, CD81-knockdown augmented the antitumor efficacy of anti-PDCD1/PD-1, yielding a pronounced survival benefit when combined with radiotherapy. Mechanistically, CD81 interacted with CD274 via its large extracellular loop (LEL) and recruited the deubiquitinase USP14 through its cytoplasmic C-terminal tail (CCT). This resultant ternary complex erased K63-linked ubiquitination at the K280 residue of CD274, thereby abolishing SQSTM1/p62-dependent recognition and subsequent autophagy-lysosomal degradation of CD274 to maintain its protein stability. Collectively, our work establishes CD81 as a pivotal bridge connecting radioresistance to immune escape via sustaining CD274 abundance in GBM, highlighting CD81 as a promising therapeutic target to optimize radioimmunotherapy. BBB: blood-brain barrier; CTLs: cytotoxic T lymphocytes; CCK-8: cell counting kit-8; ELISA: enzyme-linked immunosorbent assay; GBM: glioblastoma; IHC: Immunohistochemistry; GZMB: granzyme B; MDSCs: myeloid-derived suppressor cells; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; OS: overall survival; PFA: paraformaldehyde; PLA: proximity ligation assay; PRF1: Perforin1; STR: short tandem repeat; SQSTM1: sequestosome 1; TMT: tandem mass tag; TMZ: temozolomide; TME: tumor microenvironment; TDEs: tumor-derived exosomes; T: regulatory T cells; WT: wild type. - Source: PubMed
Publication date: 2026/09/22
Zeng LiangZhou YuchuanCai LinboZheng WangLiu XinglongLiao WeiXiao YuqiJin XiaoyaZhang JialingLai MingyaoLi HainanXu YanwuZhang JianghongPan YanWang YangShao Chunlin - Parkinson's disease (PD) is the second most prevalent neurodegenerative disorder worldwide, affecting over 8.5 million individuals globally. Its pathophysiology is multifactorial, encompassing progressive loss of dopaminergic neurons in the substantia nigra, accumulation of misfolded alpha-synuclein, mitochondrial dysfunction, oxidative stress, neuroinflammation, and impaired proteostasis. Despite decades of research, current treatments remain predominantly symptomatic, with levodopa and dopamine replacement therapies failing to halt neurodegeneration. Given the high cost and low success rate of de novo drug development, both repurposed approved drugs and mechanistically targeted investigational therapeutics have emerged as promising approaches as a strategically rational alternative that leverages established safety profiles, known pharmacokinetics, and abbreviated regulatory pathways. This review aimed to comprehensively examine the current evidence for repurposed drugs, clinically investigated therapeutic candidates, and repositioning strategies targeting the principal pathological hallmarks of Parkinson's disease: (1) alpha-synuclein aggregation and propagation, (2) oxidative stress, (3) neuroinflammation, (4) mitochondrial dysfunction, (5) lysosomal and proteasomal dysfunction, and (6) dopaminergic neurodegeneration. The review further sought to identify recurring translational challenges, propose mechanistic frameworks for rational combination therapy, and outline future directions for trial design and biomarker integration. A narrative review of published preclinical studies, clinical trials, and recent literature was conducted, focusing on repurposed compounds with mechanistic plausibility and evidence of CNS penetration relevant to PD pathology. Evidence from Phase 1-3 clinical trials and post-mortem neuropathological analyses was synthesised across each pathological hallmark. Compounds were evaluated for mechanistic specificity, pharmacokinetic suitability, and clinical translation status. Across six pathological hallmarks, repurposed agents showed disease-relevant activity, with variable clinical translation. Ambroxol, a GCase pharmacological chaperone, achieved ~ 30-34% brain penetration, increased cerebrospinal fluid alpha-synuclein in a Phase 2 trial (n = 17) regardless of GBA mutation status, and is now in Phase 3 (ASPro-PD, n = 330). N-acetylcysteine restored depleted brain glutathione, scavenged reactive oxygen species, preserved VMAT2 and tyrosine hydroxylase expression, and improved motor outcomes, with positive dopamine transporter imaging in clinical studies. Doxycycline, a BBB-penetrant antibiotic, suppressed microglial MMP-3 and MMP-9 and downregulated TNF-α, IL-1β, iNOS, and COX-2 in preclinical PD models. Metformin and its mitochondria-targeted analog Mito-Met activated AMPK signalling and reversed mitochondrial dysfunction in PD models; however, Mito-Q10 failed in a one-year clinical trial, highlighting that ~ 70% of dopaminergic neurons are already lost at symptom onset, making intervention timing a decisive variable. For proteostatic dysfunction, the USP14 inhibitor IU1 enhanced both proteasomal and autophagic flux, though neurotoxicity above 200 µM limits its therapeutic window; BIIB122, a selective LRRK2 inhibitor, achieved CNS target engagement in Phase 1/2 trials, but its Phase 3 LIGHTHOUSE study was terminated, with Phase 2b LUMA ongoing. In dopaminergic neurodegeneration, GLP-1 receptor agonists produced divergent outcomes: Exenatide-PD3 (n = 231) showed no benefit over placebo, whereas LixiPark demonstrated reduced motor progression in early-stage PD, revealing that mechanistic equivalence does not guarantee clinical equivalence across heterogeneous patient populations. Drug repurposing represents a viable and strategically advantageous approach to targeting PD pathophysiology. Repurposed compounds, including ambroxol, N-acetylcysteine, doxycycline, metformin, and GLP-1 receptor agonists, demonstrate engagement with disease-relevant mechanisms and, in several cases, preliminary evidence of clinical activity. However, a recurring translational challenge is the timing of therapeutic intervention: with approximately 70% of dopaminergic neurons already lost at symptom onset, even mechanistically sound agents may fail if administered too late. Divergent GLP-1 trial outcomes underscore that mechanistic equivalence does not guarantee clinical equivalence, and that disease-stage heterogeneity is a critical confounder. Future priorities must include: (i) precision stratification by genetic profile (e.g., GBA and LRRK2 variants); (ii) combination therapies targeting multiple interconnected hallmarks simultaneously; (iii) development of validated fluid and neuroimaging biomarkers for early-stage patient selection; and (iv) adaptive trial designs that accommodate heterogeneity across the PD population. Integration of computational tools network pharmacology, machine learning, and systems biology with biomarker-defined clinical enrichment will be essential for accelerating repurposed candidates toward meaningful disease modification. - Source: PubMed
Publication date: 2026/09/09
Dhanush YaravaNizamuddin N DNeelima SatrasalaKalpana SArla Kalyan KumarGanesh Vakkalagadda SivaSree P ChandanaRohitha Chennuru