Ask about this productRelated genes to: SAMHD1 Blocking Peptide
- Gene:
- SAMHD1 NIH gene
- Name:
- SAM and HD domain containing deoxynucleoside triphosphate triphosphohydrolase 1
- Previous symbol:
- -
- Synonyms:
- SBBI88, Mg11, HDDC1, MOP-5, AGS5
- Chromosome:
- 20q11.23
- Locus Type:
- gene with protein product
- Date approved:
- 2001-07-31
- Date modifiied:
- 2019-04-23
Related products to: SAMHD1 Blocking Peptide
Related articles to: SAMHD1 Blocking Peptide
- SAMHD1 is a mitochondria-associated cellular protein that restricts HIV-1 replication by depleting intracellular dNTP pools in non-dividing immune cells, such as macrophages, dendritic cells, and resting CD4 T cells; however, its role in host metabolism remains unclear. Building on our previous finding that SAMHD1 promotes mitochondrial membrane damage in HIV-1-infected monocytic cells, here we identify a new function for SAMHD1 in enhancing HIV-1-induced glycolysis through upregulation of hexokinase 2 (HK2). In monocytic THP-1 cells, but not differentiated macrophage-like cells, SAMHD1 amplifies HIV-1-triggered glucose uptake and basal glycolysis. Mechanistically, SAMHD1 increases HK2 expression and promotes its cytosolic accumulation, leading to elevated reactive oxygen species (ROS) production. This SAMHD1-dependent metabolic rewiring links antiviral restriction to glycolytic control and cellular stress responses. Our findings reveal a cell state-specific role for SAMHD1 in regulating glycolysis during HIV-1 infection, identify HK2 as a key effector, and uncover an unanticipated layer of host-virus interaction in monocytic cells. - Source: PubMed
Publication date: 2026/08/04
Yang HuaCheung Pak-Hin HinsonWu Li - Type I interferonopathies are a heterogeneous group of monogenic autoinflammatory disorders characterized by dysregulated type I interferon (IFN-I) signaling due to pathogenic variants that affect nucleic acid sensing, processing, or downstream signaling pathways. Mutations in genes including TREX1, RNASEH2A/B/C, SAMHD1, ADAR1, STING1 (TMEM173), PSMB8, COPA, and DNASE1L3 lead to persistent activation of innate immune pathways, particularly the cGAS-STING, MDA5, and Toll-like receptor pathways, with subsequent JAK-STAT signaling and sustained overexpression of interferon-stimulated genes. Chronic IFN-I activation promotes endothelial dysfunction, vascular inflammation, and tissue injury, providing a mechanistic link between interferonopathies and vasculitic disorders. Clinically, these conditions present with diverse manifestations, including chilblains, livedo reticularis, necrotizing cutaneous vasculopathy, panniculitis, interstitial lung disease, cerebral vasculopathy, and glomerulonephritis, often resembling autoimmune diseases such as primary central nervous system vasculitis, systemic lupus erythematosus (SLE), poliarteritis nodosa (PAN), immune complex vasculitis, and ANCA-associated vasculitis (AAV). A persistently elevated interferon gene signature represents a valuable diagnostic biomarker that distinguishes these disorders from most classical autoimmune vasculitides and facilitates early recognition. Timely genetic testing is essential to establish an accurate diagnosis, guide patient management, and avoid treatment delays. The present review summarizes the molecular mechanisms linking IFN-I dysregulation to endothelial injury and vasculitis, discusses the clinical spectrum and diagnostic challenges of monogenic interferonopathies, and highlights emerging targeted therapies, particularly Janus kinase inhibitors, that support precision medicine approaches for interferon-driven inflammatory diseases. - Source: PubMed
Publication date: 2026/08/07
Gürbüz NidaIsmayilova ShamsAhmadova GulnarÇiftçi RenaAksu GüzideBerdeli Afig - This study utilized 'Qinmi No.9' passion fruit to explore pre-harvest methyl jasmonate (MeJA) treatment effects on fruit quality and regulatory mechanisms via physiological assays, transcriptomics, and metabolomics. MeJA delayed peel yellowing, elevated total soluble solids, total flavonoid, soluble protein contents, and polygalacturonase, polyphenol oxidase, and lipoxygenase activities, but decreased titratable acidity, pectin content, and electrical conductivity, with MeJA_10 (1.0 mM MeJA) presenting optimal comprehensive performance. Transcriptomic analysis revealed that MeJA_5 (0.5 mM MeJA) mainly enriched plant hormone signal transduction and glycolysis/gluconeogenesis pathways, while MeJA_10 activated tryptophan metabolism and phenylpropanoid biosynthesis significantly; five hub genes (At2g46620, OGT, ENDOV, SAMHD1, and γ-TMT) were identified by WGCNA. Metabolomic data showed MeJA_10 induced more differentially accumulated metabolites (226) than MeJA_5 (146): MeJA_5 vs CK mainly altered organoheterocyclic compounds and phenylpropanoids/polyketides, while MeJA_10 vs CK predominantly regulated lipids/lipid-like molecules and organic acids/derivatives. Integrated analysis demonstrated that MeJA_5 enriched glycolysis/gluconeogenesis and α-linolenic acid metabolism, and MeJA_10 highly enriched starch/sucrose metabolism, tryptophan metabolism, and phenylpropanoid biosynthesis. MeJA_10 triggered more differentially expressed genes and metabolites than MeJA_5, confirming its stronger activation of metabolic and genetic expression for better fruit quality promotion. - Source: PubMed
Publication date: 2026/07/30
Lian ManjingLuo KaizhenLuo QingYan GuoyingHe FengmeiJiang ChunyaYang Xuelian - Valvular heart disease (VHD) affects over 209 million people worldwide, with calcific aortic valve disease (CAVD) playing an increasingly dominant role. However, no effective pharmacotherapies are currently available. Existing animal or cellular models are limited by insufficient physiological relevance or lack of scalability. Here, we report for the first time engineered valvular tissues (EVTs) constructed from human induced pluripotent stem cell (hiPSC)-derived valvular interstitial cells (VICs). This model was fabricated using a three-dimension (3D) hydrogel system (fibrinogen/Matrigel/collagen I), enabling anisotropic alignment of VICs with high tissue integrity that closely mimics native valve architecture and supports tissue-level biomechanical testing. Uniquely, we engineered hiPSC-derived cardiomyocytes into myocardial tissues and assembled them with EVTs to create a biomechanically active composite tissue. This design cleverly leverages the spontaneous contraction of cardiomyocytes to provide cyclic mechanical stimulation to the engineered valve, thereby validating that mechanical stress significantly exacerbates calcification. Under calcification-inducing conditions, EVTs robustly mimic key features of CAVD, including matrix remodeling, fibrosis, RUNX2 upregulation, and hydroxyapatite deposition. Biomechanical testing confirmed increased stiffness and reduced extensibility in calcified tissues, consistent with clinical observations. Furthermore, we performed time-series transcriptomic analysis throughout the in vitro culture and calcification induction process. This analysis not only confirmed a high degree of similarity between EVTs and native valves (R > 0.8) but also revealed that EVT calcification follows an osteogenic differentiation trajectory comparable to native valve calcification. Weighted gene co-expression network analysis (WGCNA) identified six potential central regulators of calcification; through subsequent small-molecule inhibition and pharmacological intervention, we definitively validated SAMHD1 as the core regulator through inflammatory signal pathway. Recombinant SAMHD1 protein significantly reduced calcification, improved tissue elasticity, and attenuated dysfunction in both static and mechanically loaded models. Our work establishes an innovative EVTs model with quantifiable tissue mechanical properties; pioneers the integration of myocardium-valve engineered tissues to construct a self-driven, cyclically stressed myocardium-valve composite model; and identifies SAMHD1 as a highly promising therapeutic target for CAVD. - Source: PubMed
Publication date: 2026/07/11
Meng XiangfuZhou QianZhu ZijinQiao WeihuaGeng BingchuanFan ZhengfengWang RuxiangGao ShanqingZhou YanyanYang PengchengDong NianguoQi YanZhang Donghui - SAMHD1 is the lone human dNTP triphosphohydrolase and is linked to antiviral defense, nucleotide pool homeostasis, chemotherapy resistance, and the autoinflammatory Aicardi-Goutières syndrome. Although its substrate specificity and nucleotide-dependent oligomerization have been extensively studied, the identity and mechanistic roles of its metal cofactors remain poorly understood. Here, we integrate selective metal enrichment, spectroscopy, biochemical reconstitution, and enzyme kinetics to define the metal requirements underlying SAMHD1 activation and catalysis. We show that robust SAMHD1 activity is preferentially supported by transition metals and that the enzyme readily assembles multiple iron-containing dinuclear active sites in solution. Iron preferentially binds to one position of the bimetallic core and promotes recruitment of a second divalent metal required for catalysis. Although manganese can substitute for iron, it alters metal-binding equilibria and less efficiently supports dinuclear cofactor assembly, highlighting a specialized organizational role for iron. In contrast, the second site remains comparatively permissive and accommodates various divalent metal ions with distinct functional consequences. Mixed-metal active sites further retain catalytic activity across redox conditions that otherwise suppress activity in homodinuclear diiron configurations, suggesting that metal plasticity buffers SAMHD1 against oxidative inhibition. Transition metals additionally act as higher-affinity allosteric activators than Mg2+, revealing that metal identity contributes to both catalytic and regulatory layers of SAMHD1 function. Cumulatively, these findings redefine the metal requirements of SAMHD1 and establish a framework in which iron-dependent active site organization and mixed-metal flexibility cooperate to sustain dNTP hydrolysis under changing cellular environments and metal flux conditions. - Source: PubMed
Calderone Logan AGizzi AnthonyPinninti SoumikaStivers James TPandelia Maria-Eirini