Atp7b
- Known as:
- Atp7b
- Catalog number:
- 038977A
- Product Quantity:
- 250ul
- Category:
- -
- Supplier:
- ABM
- Gene target:
- Atp7b
Related genes to: Atp7b
- Gene:
- ATP7B NIH gene
- Name:
- ATPase copper transporting beta
- Previous symbol:
- WND
- Synonyms:
- -
- Chromosome:
- 13q14.3
- Locus Type:
- gene with protein product
- Date approved:
- 1986-01-01
- Date modifiied:
- 2016-02-10
Related products to: Atp7b
Related articles to: Atp7b
- Cuproptosis, a recently identified form of regulated cell death, holds therapeutic promise in cancer. However, the mechanisms governing copper homeostasis and their impact on the immune landscape of clear cell renal cell carcinoma (ccRCC) remain poorly understood. A cuproptosis-related risk model was constructed to identify key prognostic factors. The role of ATP7B in ccRCC was validated using clinical cohorts, in vitro assays, and xenograft models. Mechanistic studies including Co-IP, ubiquitination assays, and Western blot were employed to elucidate the RNF186-p62-ATP7B axis. An autophagy-targeting chimera (ATAUTAC) was developed to evaluate its therapeutic and immunomodulatory potential. High ATP7B expression correlated with poor prognosis and immune evasion in ccRCC. We found that the E3 ligase RNF186 catalyzes K63-linked ubiquitination of ATP7B, driving its selective autophagic degradation via the receptor p62. In ccRCC, RNF186 downregulation leads to ATP7B accumulation, thereby limiting copper-induced proteotoxic stress. Our developed ATAUTAC effectively degraded ATP7B, disrupted mitochondrial TCA cycle metabolism, and induced canonical cuproptosis. Combining ATAUTAC with anti-PD-1 therapy significantly suppressed tumor growth and prolonged survival in vivo. Mechanistically, ATAUTAC-induced metabolic remodeling was accompanied by PD-L1 downregulation, enhanced CD8 T-cell infiltration, pro-inflammatory cytokine release, and a shift of macrophages toward an M1-like anti-tumor phenotype. This study identifies the RNF186-p62-ATP7B axis as a critical regulator of copper homeostasis in ccRCC. Targeting ATP7B via ATAUTAC offers a potent strategy to induce cuproptosis and sensitize ccRCC to immunotherapy. - Source: PubMed
Publication date: 2026/08/12
Cao MuyangDong ZhenkunXu YangyangYuan BoWu HaoGupta RadheshyamCui YanChen Hui - Cuproptosis is a recently identified form of regulated cell death driven by the direct binding of Cu⁺ to the lipoyl moiety of mitochondrial tricarboxylic acid (TCA) cycle enzymes, leading to dihydrolipoamide S-acetyltransferase (DLAT) oligomerisation, iron-sulfur cluster (Fe-S) protein depletion, and proteotoxic stress, and is uniquely dependent on mitochondrial respiration. This review critically synthesises current evidence on the role of cuproptosis in type 2 diabetes mellitus (T2DM), metabolic dysfunction-associated steatotic liver disease (MASLD), and obesity. In T2DM, three causally validated pathways of copper transporter dysregulation converge on ferredoxin 1 (FDX1)-dependent DLAT oligomerisation, with substantial FDX1 reduction in diabetic skeletal muscle providing quantitative evidence of cuproptotic commitment; however, β-cell-specific knockout studies remain critically absent. In MASLD, indirect reactive oxygen species (ROS)-mediated insulin resistance is favoured over direct copper-receptor interactions. We propose the metabolic threshold hypothesis, positing that cuproptosis represents failed adaptation to chronic lipid overload, triggered when copper influx exceeds the combined buffering capacity of ATPase copper transporting beta (ATP7B)-mediated efflux, metallothionein sequestration, and glutathione (GSH) chelation. The serum Cu/Zn ratio cannot distinguish cuproptosis from ferroptosis; precise identification requires combined detection of FDX1, DLAT, lipoic acid synthase (LIAS), and lipoyltransferase 1 (LIPT1) with mitochondrial copper content, with immunohistochemistry (IHC) for DLAT oligomerisation as the most clinically accessible surrogate marker. Copper chelators including tetrathiomolybdate and merestinib are primary agents for metabolic tissue preservation, whereas ionophores such as elesclomol are restricted to oncology, with lipid nanoparticle-based delivery platforms essential to overcome the blood-brain barrier challenge, as underscored by the neurological worsening documented in D-penicillamine-treated Wilson disease patients. The interplay between cuproptosis and ferroptosis, sharing GSH depletion but diverging at lipoylated protein aggregation versus glutathione peroxidase 4 (GPX4)-dependent lipid peroxidation, suggests dual-pathway inhibition may be necessary. Future priorities include validation of the metabolic threshold hypothesis, β-cell-specific knockout studies, standardised DLAT oligomerisation diagnostics, tissue-targeted copper modulator delivery, and integration of cuproptosis biomarkers with multi-omics and artificial intelligence for clinically stratified precision medicine. - Source: PubMed
Publication date: 2026/07/28
Chen JingFang ChaoTang ShiguoWang Haoran - Wilson disease (WD) is an autosomal recessive disorder caused by mutations in the ATP7B gene, resulting in impaired biliary copper excretion and progressive copper accumulation in multiple tissues. Ocular manifestations represent some of the most characteristic and clinically valuable features of the disease, contributing to diagnosis, monitoring, and assessment of neurological involvement. This narrative review summarizes current knowledge regarding the pathophysiology, clinical presentation, and imaging characteristics of ocular involvement in WD. Copper deposition within the eye occurs primarily through the aqueous humor, leading to accumulation in the corneal Descemet membrane and lens capsule. Kayser-Fleischer rings remain the most prevalent ocular sign being strongly associated with neurological disease, while sunflower cataracts represent a less common but highly characteristic manifestation. Anterior segment optical coherence tomography and in vivo confocal microscopy have recently improved the detection and monitoring of these lesions. Beyond copper deposition, growing evidence indicates that WD is associated with retinal and optic nerve neurodegeneration. Optical coherence tomography studies consistently demonstrate thinning of the retinal nerve fiber layer, ganglion cell complex, and macular structures, particularly in patients with neurological involvement. Electrophysiological investigations, including visual evoked potentials and electroretinography, reveal delayed neural conduction and retinal dysfunction, supporting the concept of widespread neuro-ophthalmological impairment. Optical coherence tomography angiography further identifies microvascular alterations affecting retinal and peripapillary capillary networks. Importantly, several ocular abnormalities correlate with neurological severity and may serve as non-invasive biomarkers of disease progression. Current treatments, including copper chelators and zinc therapy, can induce regression of Kayser-Fleischer rings and sunflower cataracts. Ocular assessment therefore provides a valuable window into systemic and neurological disease activity, highlighting the importance of multidisciplinary management and the potential role of emerging imaging biomarkers in Wilson disease. - Source: PubMed
Publication date: 2026/07/21
Coviltir ValeriaSabo CristinaNicula Ariadna PatriciaMarinescu Maria Cristina - In contemporary practice, elevated 24-hour urinary copper excretion (24-h UCE) often triggers referral for suspected Wilson disease (WD). In this hypercupriuric referral setting, interpretation of 24-h UCE may be distorted by spectrum effects. In this study, we aimed to compare conventional copper biomarkers in hypercupriuric referrals and evaluate whether a Leipzig-aligned ceruloplasmin (Cp) framework could provide a clinically useful triage approach. - Source: PubMed
Publication date: 2026/07/02
Zhang YuBao YijunWang YitingTao YulinLi RuijiaLiu HongliWang LiMao TianhaoJi WenjingGong YuxiangZheng SiweiZhang KaiLiu XingLi ShashaYang Yongfeng - Hepatic ischemia reperfusion injury is an important pathological factor leading to complications after hepatectomy and transplantation. Although cuproptosis has been reported as a new paradigm of programmed death triggered by copper homeostasis imbalance, its regulatory mechanisms and intervention strategies in liver IRI remain to be fully elucidated. The purpose of this study was to reveal the role of cuproptosis in liver IRI, and to elucidate the molecular mechanism by which adipose-derived stem cell exosomes (ADSC-Exos) exert therapeutic effects by regulating copper metabolism. - Source: PubMed
Publication date: 2026/07/15
Cao LeiLi PujunMa YajunLu XiangyuWang YueWang HongbinZhang JiantaoLiu Tao