Ask about this productRelated genes to: COMMD1 Blocking Peptide
- Gene:
- COMMD1 NIH gene
- Name:
- copper metabolism domain containing 1
- Previous symbol:
- C2orf5
- Synonyms:
- MURR1, MGC27155
- Chromosome:
- 2p15
- Locus Type:
- gene with protein product
- Date approved:
- 2003-08-26
- Date modifiied:
- 2016-01-07
Related products to: COMMD1 Blocking Peptide
Related articles to: COMMD1 Blocking Peptide
- Mutations in superoxide dismutase 1 (SOD1) compromise its metal-binding capacity, resulting in protein misfolding and aggregation, which ultimately induces cellular apoptosis in amyotrophic lateral sclerosis (ALS). Copper metabolism domain containing 1 (COMMD1), a gene implicated in copper homeostasis, has not been thoroughly characterized in the context of ALS pathogenesis. In this study, we identified elevated COMMD1 expression in ALS, potentially contributing to diminished copper incorporation into SOD1. Knockdown of COMMD1 enhanced palmitoylation of the copper chaperone for SOD1 (CCS), facilitating its membrane translocation and promoting copper loading into SOD1, thereby conferring neuroprotection in ALS. Mechanistically, we established that COMMD1 knockdown augments CCS palmitoylation via activation of the hypoxia inducible factor 1 subunit alpha (HIF-1α)/fatty acid synthase (FASN) signaling axis. In vivo investigations utilizing male hSOD1 transgenic mice demonstrated that COMMD1 deficiency markedly ameliorated the deterioration of motor function and prolonged survival duration. These findings collectively suggest that COMMD1 represents a potential therapeutic target for ALS intervention. Superoxide dismutase 1 (SOD1) was the first identified mutant gene associated with amyotrophic lateral sclerosis (ALS). Mutations in SOD1 compromise its metal-binding function, resulting in neuronal apoptosis, a hallmark of ALS pathogenesis. Utilizing the SOD1 models of ALS, our findings revealed that COMMD1 deficiency significantly elevates copper incorporation into SOD1, consequently attenuating cellular apoptosis. These results suggest that targeted inhibition of COMMD1 could represent a potential therapeutic strategy for ALS treatment. - Source: PubMed
Publication date: 2026/05/19
Su XiaoliTan XingliWang YingLiang WeiweiWang DiHuo DiWang HongyongQi YanZhang WenmoHan LingZhang DongmeiWang MingXu JingWang ShuyuWang JingFeng Honglin - Intervertebral disc degeneration (IDD) is a major cause of low back pain, yet the biological effects of commonly used non-steroidal anti-inflammatory drugs (NSAIDs) on disc cells remain poorly understood. Celecoxib is widely prescribed for IDD-related pain, but its direct influence on IDD has not been systematically examined. Here, we identify a concentration-dependent biphasic effect of celecoxib on nucleus pulposus (NP) cells and uncover the mechanism that converts celecoxib from protective to detrimental. Using interleukin-1β-stimulated NP cells and rat IDD models, we show that low-dose celecoxib (≤20 µm) suppresses inflammation and preserves extracellular matrix (ECM). In contrast, high-dose celecoxib (>20 µm) activates a previously unrecognized heat shock protein 90 (HSP90)/RING-box protein 1 (RBX1)/cuproptosis axis, leading to copper accumulation, mitochondrial stress, and ECM degradation. Mechanistically, elevated celecoxib induces HSP90 upregulation, which stabilizes RBX1 by reducing its K48-linked ubiquitination. Accumulated RBX1 promotes ATPase copper transporting beta (ATP7B) and its regulator copper metabolism domain containing 1 (COMMD1) degradation, thereby triggering cuproptosis. Pharmacologic inhibition of HSP90 or cuproptosis effectively reverses the detrimental effects of high-dose celecoxib in vivo. Together, these findings define a strict therapeutic window for celecoxib in IDD and reveal a novel HSP90/RBX1-mediated cuproptosis pathway that mediates its dual effects. - Source: PubMed
Publication date: 2026/05/04
Guo YoufengXiao HongjuBa ShenghaoZhou YuWang BijunYu BinHuang YufengZhao HaihongChen Zhefan StephenShen NaBa ZhaoyuWu Desheng - Annotation of regulatory elements is essential for understanding mechanisms underlying gene regulation, particularly tissue-specific regulation in human and animals. Here, we characterize 274,682 enhancers and 25,975 promoters across 24 tissues from an adult female sheep using ChIP-seq, ATAC-seq, CAGE-seq, RRBS, WGBS, and RNA-seq. We identify seven neural development-related genes with over 10 enhancers in brain tissues, highlighting the role of tissue-specific regulation. Cis-regulatory enhancer-promoter combinations provide insights into tissue-specific enhancers, such as the cerebellum-specific enhancer (chr15: 57390520-57390685) regulating BDNF, which is expressed in both the cerebellum and cerebral cortex. Comparative analysis of enhancer-promoter combinations in human, mouse, pig, cattle, and sheep reveals ruminant-specific pathways, including pentose catabolism and long-chain fatty acid import regulation. A milk fat yield quantitative trait locus (QTL) identified within an enhancer interacts with the fat metabolism-related gene COMMD1, and a birth weight-associated QTL detected within a cerebellum-specific enhancer regulates XKR4. This study provides a robust framework for exploring cis-regulatory mechanisms and tissue-specific regulation, advancing the functional annotation of the sheep reference genome. - Source: PubMed
Publication date: 2026/03/16
Xie ShangqianDavenport Kimberly MSalavati MazdakCaulton AlexClark Emily LArchibald Alan LClarke Shannon MBrauning RudigerMassa Alisha TMousel Michelle RWhite Stephen NWorley Kim CMurdoch Gordon KBecker GabrielleStegmiller Morgan RKhilji Sarem FShira Katie AOlagunju Temitayo AHadfield TracyMcKay Stephanie DRosen Benjamin DCockett Noelle ESmith Timothy P LMurdoch Brenda M - This study investigated the role of copper metabolism MURR1 domain-containing 1 (COMMD1) in Talaromyces marneffei (TM)-induced osteomyelitis (OM) and its regulation of osteoclast differentiation via the NF-κB pathway. - Source: PubMed
Publication date: 2025/11/21
Zhang YiYang FayunZhao WeilunWei RufeiZeng GaofengZong Shaohui - Cystic fibrosis is an autosomal recessive disease caused by mutations in the CFTR gene, leading to progressive respiratory decline and reduced life expectancy. The most common mutation, CFTR-F508del, results in mislocalised and non-functional protein. Although triple therapy with elexacaftor/tezacaftor/ivacaftor (ETI) is prescribed for patients carrying this mutation, some biological defects remain unresolved. We previously identified COMMD1 as a potential therapeutic target, as its overexpression enhances CFTR-WT plasma membrane localisation. CIGB-552, a cell-penetrating peptide discovered in 2013, stabilises COMMD1. This study evaluates its therapeutic potential in cystic fibrosis. - Source: PubMed
Publication date: 2025/08/14
Simonneau BenjaminSimon StéphanieDuriez BénédicteGuguin AurélieBecq FrédéricMirval SandraCoraux ChristelleDegrugillier FannyCostes BrunoVallespi Maribel GFanen PascaleAissat Abdel