Ask about this productRelated genes to: Cyb5r4 Blocking Peptide
- Gene:
- CYB5R4 NIH gene
- Name:
- cytochrome b5 reductase 4
- Previous symbol:
- NCB5OR
- Synonyms:
- b5+b5R, dJ676J13.1
- Chromosome:
- 6q14.2
- Locus Type:
- gene with protein product
- Date approved:
- 2003-08-27
- Date modifiied:
- 2014-11-18
Related products to: Cyb5r4 Blocking Peptide
Related articles to: Cyb5r4 Blocking Peptide
- Diabetic kidney disease (DKD) progression involves early proximal tubular injury, which precedes podocyte injury. The protective role of the protein Klotho in DKD is well-documented, but its impact on early tubular injury and mitochondrial dysfunction in proximal tubule epithelial cells (PTECs) remains underexplored. This study aimed to determine whether Klotho alleviates DKD by targeting mitochondrial dysfunction in PTECs and to uncover the molecular mechanisms involved. - Source: PubMed
Publication date: 2026/03/28
Gan ChunZhou XindiQiu LanChen DanShi YuluYang QingJiang HuiminXiao HanChen WanbingYang XuejunChen YaxiWang MoYang HaipingJiang WeiLi Qiu - Angiogenesis is essential for revascularization in peripheral artery disease (PAD), yet pro-angiogenic therapies remain inconsistent. Here, we identify a cytosolic reductase, CYB5R4, as an intrinsic regulator of endothelial proliferation and ischemia-induced angiogenesis. In mice, global haploinsufficiency or inducible endothelial deletion of delayed perfusion recovery after femoral artery ligation and reduced capillary expansion. CYB5R4 is known to promote stearoyl-CoA desaturase (SCD) activity and is required for the synthesis of monounsaturated fatty acids. In human endothelial cells, silencing impaired proliferation with G1-S arrest that was not rescued by monounsaturated fatty acids and differed from the loss of SCD, indicating an SCD-independent mechanism. RNA sequencing with Bayesian network inference highlighted the ribonucleotide-reductase subunit RRM2 as a key downstream mediator. RRM2 overexpression partially restored proliferation. Integrated untargeted metabolomics and targeted nucleotide quantification revealed an imbalanced nucleotide pool in CYB5R4-deficient cells. These findings support a model in which CYB5R4 sustains endothelial proliferation and ischemia-driven angiogenesis by maintaining RRM2-dependent nucleotide balance. Targeting the CYB5R4-RRM2 axis may improve therapeutic angiogenesis in PAD. - Source: PubMed
Publication date: 2025/09/20
Yuan ShuaiHahn Scott AColussi Nicole CMullett Steven JGelhaus Stacy LSchopfer Francisco JStraub Adam C - Osteoporosis is a prevalent metabolic bone disorder with complex molecular underpinnings. Emerging evidence implicates endoplasmic reticulum stress (ERS) in its pathogenesis; however, systematic exploration of ERS-related genes (ERSRGs) remains limited. This study aimed to identify ERS-related differentially expressed genes (ERSRDEGs) in osteoporosis, construct a diagnostic model, and elucidate associated molecular mechanisms. Three osteoporosis datasets (GSE56815, GSE230665, and GSE7429) were integrated after batch effect correction and normalization. ERSRGs were curated from GeneCards, and ERSRDEGs were identified by intersecting co-differentially expressed genes (Co-DEGs) across datasets. Functional enrichment (gene set enrichment analysis [GSEA], gene set variation analysis [GSVA], Gene Ontology [GO], and Kyoto Encyclopedia of Genes and Genomes [KEGG]) and immune infiltration analyses were performed. Diagnostic models were developed using support vector machine (SVM) and least absolute shrinkage and selection operator (LASSO) regression, validated via receiver operating characteristic (ROC) curves, nomograms, and decision curve analysis. Experimental validation included immunohistochemistry and quantitative reverse transcription polymerase chain reaction (qRT-PCR) in ovariectomized (OVX) mice. Regulatory networks (TF-miRNA-RBP-drug) and protein structure predictions were generated using bioinformatic tools. Fifty six ERSRDEGs were identified, enriched in apoptosis, autophagy, and cytokine signaling pathways. A diagnostic model comprising seven genes (CYB5R4, RAB1B, UFSP2, RNF13, SERP1, CES2, and C1QBP) demonstrated high accuracy (area under the curve (AUC) > 0.9) in both training and validation datasets. Immune infiltration analysis revealed distinct patterns of activated B cells, CD8 T cells, and macrophages between high- and low-risk groups. Regulatory networks highlighted interactions with 52 transcription factors (TFs), 42 miRNAs, and 27 therapeutic compounds. Experimental validation in OVX mice confirmed upregulated expression of C1QBP, CYB5R4, RAB1B, and UFSP2 at protein/mRNA levels, aligning with bioinformatic predictions. This study establishes ERSRDEGs as critical players in osteoporosis pathogenesis and provides a clinically translatable seven-gene diagnostic model for early osteoporosis detection. The integration of multiomics analyses uncovered key pathways, immune dynamics, and regulatory networks, while experimental validation reinforced the role of specific ERSRGs. These findings provide novel insights into ERS-mediated mechanisms and therapeutic targets for osteoporosis management. - Source: PubMed
Publication date: 2025/08/30
Zhu YirenYang XiuLu YunanHe JiayuLiu BoZhang YongfaZhang Zhengchao - Ovarian cancer (OC) is a significant health problem often diagnosed at an advanced stage due to the lack of early symptoms and effective screening methods. This study aimed to explore the role of gene methylation as a potential biomarker for ovarian cancer. - Source: PubMed
Publication date: 2025/06/20
Gonc AysegulSukruoglu Erdogan OzgeKilic Erciyas SedaCelik Demirbas BetulDinc AhmetPasin OzgeSaip PınarYazici HulyaTuncer Seref Bugra - Serine/Threonine phosphoprotein phosphatases (PPPs, PP1-PP7) are conserved metalloenzymes and central to intracellular signaling in eukaryotes, but the details of their regulation is poorly understood. To address this, we performed genome-wide CRISPR knockout and focused base editor screens in PPP perturbed conditions to establish a high-resolution functional map of PPP regulation that pinpoints novel regulatory mechanisms. Through this, we identify the orphan reductase CYB5R4 as an evolutionarily conserved activator of PP4 and PP6, but not the closely related PP2A. Heme binding is essential for CYB5R4 function and mechanistically involves the reduction of the metal ions in the active site. Importantly, CYB5R4-mediated activation of PP4 is critical for cell viability when cells are treated with DNA damage-inducing agents known to cause oxidative stress. The discovery of a dedicated PPP reductase points to shared regulatory principles with protein tyrosine phosphatases, where specific enzymes dictate activity by regulating the active site redox state. In sum, our work provides a resource for understanding PPP function and the regulation of intracellular signaling. - Source: PubMed
Publication date: 2025/02/16
Meeusen BobAmbjørn Sara MVeis JiriRiley Rachel CVit GianmatteoBrauer Brooke LMøller Mads HGreiner Elora CChan Camilla BWeisser Melanie BGarvanska Dimitriya HZhu HaoDavey Norman EKettenbach Arminja NOgris EgonNilsson Jakob