Affinage

JAG1

Protein jagged-1 · UniProt P78504

Length
1218 aa
Mass
133.8 kDa
Annotated
2026-04-28
100 papers in source corpus 26 papers cited in narrative 26 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

JAG1 is a transmembrane ligand of the Notch signaling pathway that controls cell-fate decisions across diverse developmental and homeostatic contexts by activating Notch receptors on neighboring cells (trans-activation) and inhibiting Notch receptors within the same cell (cis-inhibition). Surface presentation of JAG1 is essential for signaling and is regulated by glycosylation-dependent ER quality control, Mind bomb (Mib)-mediated ubiquitylation, SNX17/retromer-dependent endosomal recycling, and gamma-secretase/GSK3-dependent proteolytic processing (PMID:11157803, PMID:20573700, PMID:25408867, PMID:35819850). Beyond canonical Notch activation, proteolytic cleavage of JAG1 generates a nuclear-targeted intracellular domain (JICD1) that forms a transcriptional cofactor complex with DDX17, SMAD3, and TGIF2 to drive SOX2 expression and oncogenic transformation (PMID:36417870, PMID:31506332). Haploinsufficiency of JAG1 causes Alagille syndrome, and the developing heart is especially sensitive to reduced JAG1 dosage (PMID:9585603, PMID:12649809).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 1997 High

    Identification of JAG1 as a Notch ligand mapping to the Alagille syndrome critical region established the gene as a candidate for a major developmental disorder and anchored it within the Notch signaling framework.

    Evidence CpG island cloning and full-length cDNA characterization with chromosomal mapping to 20p12

    PMID:9268641

    Open questions at the time
    • No functional signaling data at this stage
    • Causative role in Alagille syndrome not yet proven
  2. 1998 High

    Demonstration that diverse loss-of-function mutations — including whole-gene deletions — cause Alagille syndrome established haploinsufficiency as the disease mechanism, ruling out dominant-negative effects.

    Evidence SSCP screening and FISH on 54 AGS probands identifying deletions, frameshifts, nonsense, splice-site, and missense mutations

    PMID:9585603

    Open questions at the time
    • Tissue-specific sensitivity to dosage not yet explored
    • Molecular basis of variable expressivity unknown
  3. 2001 High

    Functional dissection of disease-associated missense mutations revealed that defective glycosylation and ER retention prevent surface delivery of JAG1, directly linking protein trafficking to loss of Notch signaling activity.

    Evidence Cell-surface expression, glycosylation analysis, Notch reporter assays, and immunofluorescence on R184H and L37S mutants

    PMID:11157803

    Open questions at the time
    • Chaperone/ERAD machinery handling misfolded JAG1 not identified
    • In vivo trafficking dynamics unresolved
  4. 2003 High

    Characterization of the leaky G274D allele showed that partial surface delivery produces an intermediate signaling output, and the cardiac-specific phenotype demonstrated the heart's heightened sensitivity to JAG1 dosage — establishing a tissue-specific threshold model.

    Evidence Glycosylation and surface expression assays combined with genotype–phenotype analysis in a 13-member family

    PMID:12649809

    Open questions at the time
    • Molecular basis of tissue-specific dosage sensitivity unknown
    • Whether other organs have distinct thresholds untested
  5. 2010 High

    Identification of Mib-dependent ubiquitylation of Jag1 as a prerequisite for trans-activation of Notch resolved how the ligand's endocytic trafficking enables receptor activation in signal-receiving cells.

    Evidence Ubiquitylation assays and genetic epistasis in zebrafish notochord and muscle patterning

    PMID:20573700

    Open questions at the time
    • Specific ubiquitin chain type and lysine sites on JAG1 not mapped
    • Whether other E3 ligases contribute to JAG1 regulation unresolved
  6. 2012 Medium

    Discovery that SNX17 binds Jag1 and promotes retromer-dependent recycling to the plasma membrane revealed a post-endocytic mechanism controlling the pool of signaling-competent JAG1 at the cell surface.

    Evidence Biochemical binding assays and vesicular trafficking assays in zebrafish neurogenesis and pancreas models

    PMID:25408867

    Open questions at the time
    • Mammalian validation of SNX17-JAG1 recycling pathway not reported
    • Whether recycling modulates cis- vs. trans-signaling untested
  7. 2012 High

    Conditional Jag1 deletion in surface ectoderm demonstrated an essential role for JAG1-Notch signaling in lens vesicle separation, extending JAG1's known developmental functions to eye morphogenesis.

    Evidence AP2α-Cre conditional knockout mouse with histological analysis

    PMID:22275127

    Open questions at the time
    • Downstream targets mediating lens separation not identified
    • Which Notch receptor is the relevant partner in this context unknown
  8. 2017 High

    ChIP-qPCR showing HES1/HEY1 binding to the Gdnf promoter downstream of JAG1-Notch signaling in Sertoli cells established a direct transcriptional mechanism by which spermatogonial stem cells create negative feedback on their own niche.

    Evidence Double-mutant mouse model, ChIP-qPCR, dual luciferase assay, and co-culture

    PMID:28051360

    Open questions at the time
    • Whether additional JAG1-dependent targets regulate the niche untested
    • Quantitative relationship between JAG1 levels and GDNF output not determined
  9. 2019 High

    Genetic epistasis in coronary vasculature revealed that JAG1 and DLL4 act as antagonistic Notch ligands controlling arterial vs. capillary fate, with EphrinB2 identified as a critical downstream effector — establishing a ligand-competition model for vascular patterning.

    Evidence Multiple conditional endocardial KO mice, ventricular explant rescue, and primary human EC assays

    PMID:31789590

    Open questions at the time
    • How differential receptor glycosylation (Fringe) tunes Jag1 vs. Dll4 preference in coronary ECs not fully defined
  10. 2019 High

    Discovery that KRAS-driven ADAM17 cleavage of JAG1 generates a nuclear-targeted intracellular domain (Jag1-ICD) that promotes EMT and chemoresistance independently of canonical Notch activation revealed a ligand-intrinsic signaling mode.

    Evidence In vitro and in vivo CRC models with KRAS/ADAM17 inhibition and Jag1-ICD nuclear translocation assays

    PMID:31506332

    Open questions at the time
    • Direct transcriptional targets of Jag1-ICD in CRC not genome-wide mapped
    • Structural basis of nuclear import undefined
  11. 2022 High

    ChIP-seq and proteomics defined the JICD1–DDX17–SMAD3–TGIF2 complex as a transcriptional unit driving SOX2 expression and oncogenic transformation, providing the first genome-wide map of JICD1 chromatin occupancy.

    Evidence ChIP-seq, transcriptomics, proteomics, co-IP, and in vitro/in vivo tumor assays in astrocytes

    PMID:36417870

    Open questions at the time
    • Whether JICD1 complex composition varies across cell types unknown
    • Structural basis of DDX17–JICD1 interaction unresolved
  12. 2022 High

    Demonstration that JAG1-NOTCH4 signaling is activated by disturbed blood flow and promotes atherosclerosis established JAG1 as a mechanosensing effector in endothelial cells.

    Evidence EC-specific Jag1 conditional KO mice, porcine/murine artery models, light-sheet imaging, and single-cell RNA-seq

    PMID:36044575

    Open questions at the time
    • Mechanosensor upstream of JAG1 induction by disturbed flow not identified
    • Whether NOTCH4 is the sole receptor in this context not genetically tested
  13. 2023 High

    Mathematical modeling validated against multiple knockout phenotypes formally distinguished JAG1-mediated cis-inhibition from DLL1-mediated trans-activation in pancreatic progenitors, showing that cis-inhibition drives exit from multipotency.

    Evidence Quantitative model benchmarked against Notch pathway conditional KO mice, inhibitor studies, and Hes1 oscillation measurements

    PMID:36681690

    Open questions at the time
    • Biochemical parameters of cis vs. trans binding affinities in pancreatic cells not directly measured
    • Whether cis-inhibition operates similarly in non-pancreatic tissues not tested
  14. 2024 High

    Reconstitution of Notch activation by soluble multivalent JAG1 on DNA origami without pulling force challenged the obligate mechanical-force model, suggesting that ligand clustering alone can suffice for receptor activation.

    Evidence DNA origami nanopattern display with Notch reporter assays in neuroepithelial stem-like cells and chimeric ligand controls

    PMID:38238313

    Open questions at the time
    • Whether force-independent activation occurs in vivo or is an in vitro phenomenon
    • Threshold valency and spacing requirements not fully defined
  15. 2024 High

    HOXA5 was shown to directly repress JAG1 transcription, and epigenetic silencing of HOXA5 derepresses JAG1 to promote kidney fibrosis, revealing an upstream transcriptional checkpoint on JAG1 expression.

    Evidence ChIP of HOXA5 at the JAG1 promoter, conditional Hoxa5 KO/knockin mice, and 5-Aza treatment with genome-wide methylation analysis

    PMID:38521405

    Open questions at the time
    • Whether HOXA5 regulates JAG1 in non-renal tissues unknown
    • Other transcription factors cooperating at the JAG1 promoter not mapped genome-wide

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the structural basis of cis- vs. trans-engagement of Notch receptors by JAG1, the full spectrum of JICD1 nuclear targets and complex partners across cell types, the identity of the mechanosensor upstream of flow-induced JAG1, and whether force-independent Notch activation by multivalent JAG1 occurs in physiological settings.
  • No crystal structure of JAG1–Notch cis-complex
  • JICD1 target genes mapped only in astrocytes and CRC
  • In vivo relevance of force-independent activation untested

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0048018 receptor ligand activity 6 GO:0098772 molecular function regulator activity 2 GO:0140110 transcription regulator activity 2
Localization
GO:0005886 plasma membrane 4 GO:0005634 nucleus 2 GO:0005783 endoplasmic reticulum 2 GO:0005768 endosome 1
Pathway
R-HSA-162582 Signal Transduction 9 R-HSA-1266738 Developmental Biology 4 R-HSA-1643685 Disease 4 R-HSA-74160 Gene expression (Transcription) 2
Partners
DDX17MIB1NOTCH1NOTCH2NOTCH4SMAD3SNX17TGIF2
Complex memberships
JICD1-DDX17-SMAD3-TGIF2

Evidence

Reading pass · 26 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1997 JAG1 was identified and cloned as the human homolog of rat Jagged1, localized to chromosome 20p12 within the Alagille syndrome critical region, and shown to encode a Notch ligand expressed during development. CpG island cloning, full-length cDNA cloning, expression analysis, physical mapping Genomics High 9268641
1998 Loss-of-function mutations (deletions, frameshifts, nonsense, splice-site, and missense) distributed across JAG1 cause Alagille syndrome, with haploinsufficiency established as the primary disease mechanism since total gene deletions phenocopy intragenic mutations. SSCP mutation screening, FISH for whole-gene deletions, genotype-phenotype correlation in 54 AGS probands American journal of human genetics High 9585603
2001 Missense mutations R184H and L37S in JAG1 cause defective intracellular transport: the mutant proteins are abnormally glycosylated, retained intracellularly (likely in the ER), fail to reach the cell surface, and lose Notch signaling activity; two other missense changes (P163L, P871R) retain normal glycosylation, surface localization, and signaling, indicating they are polymorphisms. Cell-surface expression assays, glycosylation analysis, Notch signaling reporter assays, immunofluorescence localization Human molecular genetics High 11157803
2003 The JAG1-G274D missense mutation produces two protein populations: one abnormally glycosylated and retained intracellularly, and one normally glycosylated that reaches the cell surface and signals to Notch; this leaky allele yields >50% but <100% surface JAG1, and the cardiac-specific phenotype demonstrates the developing heart is more sensitive than liver to reduced JAG1 dosage. Glycosylation analysis, cell-surface expression assays, Notch reporter assays, temperature-sensitivity experiments, genotype-phenotype analysis in 13-member family American journal of human genetics High 12649809
2010 Mind bomb (Mib) ubiquitylates Jagged1 (Jag1) in signal-emitting cells and is essential for Jag1 to activate Notch signaling; in zebrafish, Mib-Jag1-Notch signaling controls cell-fate decisions between vacuolated and non-vacuolated notochord cells, affecting basement membrane formation and muscle pioneer patterning. Zebrafish loss- and gain-of-function genetics, ubiquitylation assays, live imaging Development (Cambridge, England) High 20573700
2010 JAG1 missense mutations identified in tetralogy of Fallot and pulmonic stenosis patients display heterogeneous effects on protein localization, post-translational modification (glycosylation), and Notch signaling activation, with some acting through complete haploinsufficiency and others retaining partial function. Protein localization assays, glycosylation analysis, Notch signaling reporter assays in cell lines Human mutation High 20437614
2011 JAG1-induced Notch signaling directly transcriptionally activates urokinase plasminogen activator (uPA) in breast cancer cells via a CBF-1 binding site in the uPA promoter, linking JAG1-Notch to the plasminogen activator system and cancer progression. siRNA knockdown, microarray profiling, luciferase promoter mutational analysis, CBF-1 binding site identification Cancer research High 21199807
2012 JAG1-mediated Notch signaling is required for lens vesicle separation from the surface ectoderm during mouse lens development, demonstrated by AP2α-Cre-driven conditional deletion of Jag1 or Rbpj. Conditional knockout mouse, Cre-lox genetics, histological analysis Developmental dynamics High 22275127
2012 JAG1 is the primary upregulated Notch ligand in adrenocortical carcinoma (ACC) and enhances cell proliferation in a non-cell-autonomous manner through activation of canonical Notch signaling in adjacent cells, as demonstrated by JAG1 knockdown and dominant-negative MAML (DNMaml) inhibition. JAG1 knockdown (shRNA), co-culture FACS proliferation assay, Notch reporter (luciferase), DNMaml inhibition Clinical cancer research High 22427350
2012 SNX17, a sorting nexin, binds to Jag1 and promotes retromer-dependent recycling of Jag1 to the plasma membrane, thereby regulating Notch pathway activity and cell fate in zebrafish neurogenesis and pancreas development. Biochemical binding assays, zebrafish genetics, vesicular trafficking assays Cell regeneration (London, England) Medium 25408867
2014 JAG1 mediates pro-proliferative signals in medulloblastoma via activation of NOTCH2 receptor and induction of HES1 expression. JAG1 knockdown, Notch reporter assays, expression profiling of MB tumor cohorts Acta neuropathologica communications Medium 24708907
2015 HCMV infection downregulates Jag1 protein levels and alters its intracellular localization in neural progenitor cells through enhanced proteasomal degradation; viral tegument proteins pp71 and UL26 reduce both NICD1 and Jag1 protein levels, disrupting Notch signaling. Viral infection experiments, immunofluorescence localization, proteasome inhibitor rescue, transient expression of viral proteins Journal of virology Medium 25903338
2016 JAG1-mediated Notch signaling regulates differentiation of basal stem/progenitor cells into secretory cells in the human airway epithelium; JAG1 overexpression increases secretory cell differentiation while JAG1 knockdown decreases secretory cell gene expression without affecting ciliated cell differentiation. JAG1 overexpression and siRNA knockdown in human airway basal cells, air-liquid-interface culture, gene expression analysis Stem cell reviews and reports Medium 27216293
2017 In Sertoli cells, JAG1 expressed on spermatogonial stem/progenitor cells activates Notch signaling, leading to HES1 and HEY1 transcriptional repressors binding the Gdnf promoter and directly downregulating GDNF expression, thereby creating a negative feedback on SSC self-renewal. Double-mutant mouse model, dual luciferase assay, ChIP-qPCR, in vitro co-culture Stem cells and development High 28051360
2019 In colorectal cancer with mutant KRAS, ADAM17 downstream of KRAS/ERK signaling cleaves JAG1 to generate a nuclear-targeted intracellular domain (Jag1-ICD) that acts as a transcriptional co-factor to promote EMT, tumor growth, and chemoresistance independent of canonical Notch activation. In vitro and in vivo tumor models, KRAS/ADAM17 inhibition, Jag1-ICD nuclear translocation assays, EMT/chemoresistance phenotypic assays Cancer research High 31506332
2019 In the developing coronary vasculature, JAG1 and DLL4 act as antagonistic Notch ligands: endocardial JAG1 removal blocks sinus venosus capillary sprouting, while forced DLL4 or Mfng expression blocks arterial differentiation; EphrinB2 is identified as a critical downstream effector of the Dll4-Jag1 antagonism in arterial morphogenesis. Conditional endocardial knockout mice, forced expression, ventricular explant angiogenic rescue, primary human endothelial cell assays eLife High 31789590
2019 In the ovary, oocyte-expressed JAG1 is necessary for activation of Notch signaling in granulosa cells; oocyte ablation or oocyte-specific Jag1 deletion suppresses Notch reporter activity in granulosa cells, and recombinant JAG1 enhances Notch target gene expression in granulosa cells. Transgenic Notch reporter mice, germ cell ablation (busulfan), KitWv/Wv mice, oocyte-specific Jag1 conditional KO, recombinant JAG1 treatment Endocrinology High 31609444
2020 In developing pancreas, JAG1 expressed in pro-acinar cells (PACs) is critical for specification of bipotent progenitors (BPs); Jag1 restrains MPC growth, and Jag1;Dll1 double mutants completely lose BPs, demonstrating that JAG1 modulates oscillating Dll1-Notch-Hes1 signaling to coordinate progenitor fate. Conditional knockout mice (Jag1, Dll1, double mutants), live imaging of Hes1 oscillations, lineage tracing Developmental cell High 32059775
2022 The JAG1 intracellular domain (JICD1), generated by proteolytic processing analogous to NICD formation, acts as a transcriptional cofactor by forming a complex with DDX17, SMAD3, and TGIF2, increasing SOX2 expression and inducing oncogenic transformation including tumor formation, invasiveness, stemness, and therapy resistance in astrocytes. ChIP-seq, transcriptome analysis, proteomics, co-IP, functional in vitro/in vivo tumor assays Cell reports High 36417870
2022 Disturbed blood flow activates the JAG1-NOTCH4 signaling pathway in endothelial cells; EC-specific genetic deletion of Jag1 reduces atherosclerosis at sites of disturbed flow, and single-cell RNA sequencing shows Jag1 suppresses EC subsets that proliferate and migrate, establishing JAG1-NOTCH4 as a mechanosensing pathway promoting atherosclerosis. EC-specific Jag1 conditional KO mice, porcine/murine artery models, light-sheet imaging, single-cell RNA sequencing Science advances High 36044575
2022 JAG1 and JAG2 undergo gamma-secretase complex (GSC)-dependent and glycogen synthase kinase 3-dependent post-translational modifications that generate a JAG1 C-terminal peptide and regulate full-length JAG2 abundance on the cell surface, creating distinct assemblies that regulate Notch signal strength and determine tracheobronchial stem/progenitor cell fate. GSC inhibitors, neutralizing peptides/antibodies, RNA-Seq, biochemical surface expression assays, air-liquid-interface cultures JCI insight Medium 35819850
2023 Jag1-mediated cis-inhibition of Notch receptors in multipotent pancreatic progenitors is essential for exiting the multipotent state, while Dll1-mediated trans-activation is required for adopting bipotent fate; a mathematical model incorporating cis- and trans-interactions recapitulates in vivo knockout phenotypes. Mathematical modeling validated against Notch pathway knockout mice, small molecule inhibitor studies, Hes1 oscillation measurements Nature communications High 36681690
2024 Soluble, multivalent JAG1 displayed on DNA origami nanopatterns activates Notch signaling in neuroepithelial stem-like cells without requiring a pulling force, challenging the prevailing model that mechanical force is obligatory for Notch receptor activation. DNA origami nanopattern display, Notch signaling reporter assays in neuroepithelial cells, chimeric ligand controls ruling out confounds Nature communications High 38238313
2024 HOXA5 directly binds the JAG1 gene promoter and represses JAG1 transcription; loss of HOXA5 via DNA hypermethylation leads to JAG1 upregulation, consequent NOTCH pathway activation, and kidney fibrosis in mice and humans. ChIP (HOXA5 binding to JAG1 promoter), conditional Hoxa5 KO and knockin mice, DNA methyltransferase inhibitor 5-Aza, genome-wide methylation analysis Kidney international High 38521405
2009 KSHV vFLIP induces JAG1 expression through an NF-κB-dependent mechanism in lymphatic endothelial cells, and JAG1-stimulated signaling through NOTCH4 suppresses cell-cycle genes in adjacent cells, promoting cellular quiescence. KSHV vFLIP/vGPCR expression, NF-κB inhibition, gene expression profiling, Notch signaling assays PLoS pathogens Medium 19816565
2017 In HTLV-1-transformed ATL cells, JAG1 overexpression is driven by the viral Tax protein and cellular factors miR-124a, STAT3, and NFATc1; blockade of JAG1 signaling dampens NOTCH1 downstream activity and limits ATL cell migration. shRNA knockdown, neutralizing antibodies, RT-PCR, FACS, immunohistochemistry, migration assays Journal of hematology & oncology Medium 30231940

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2007 High-level JAG1 mRNA and protein predict poor outcome in breast cancer. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 180 17507991
1998 Spectrum and frequency of jagged1 (JAG1) mutations in Alagille syndrome patients and their families. American journal of human genetics 168 9585603
2007 JAG1 expression is associated with a basal phenotype and recurrence in lymph node-negative breast cancer. Breast cancer research and treatment 126 17990101
2003 Consequences of JAG1 mutations. Journal of medical genetics 116 14684686
2015 Jagged1 (JAG1): Structure, expression, and disease associations. Gene 114 26548814
2019 Alagille syndrome mutation update: Comprehensive overview of JAG1 and NOTCH2 mutation frequencies and insight into missense variant classification. Human mutation 112 31343788
2017 IL-1β-induced NF-κB activation down-regulates miR-506 expression to promotes osteosarcoma cell growth through JAG1. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 99 28926924
2016 Insights from Mendelian Interferonopathies: Comparison of CANDLE, SAVI with AGS, Monogenic Lupus. Journal of molecular medicine (Berlin, Germany) 93 27678529
2010 Jagged1 (JAG1) mutations in patients with tetralogy of Fallot or pulmonic stenosis. Human mutation 92 20437614
2019 NSD2 circular RNA promotes metastasis of colorectal cancer by targeting miR-199b-5p-mediated DDR1 and JAG1 signalling. The Journal of pathology 82 30666650
2005 AGS proteins: receptor-independent activators of G-protein signaling. Trends in pharmacological sciences 82 16084602
2010 Mib-Jag1-Notch signalling regulates patterning and structural roles of the notochord by controlling cell-fate decisions. Development (Cambridge, England) 77 20573700
2006 Porphyran induces apoptosis related signal pathway in AGS gastric cancer cell lines. Life sciences 73 16876203
2021 The effect of paclitaxel on apoptosis, autophagy and mitotic catastrophe in AGS cells. Scientific reports 71 34873207
2001 Defective intracellular transport and processing of JAG1 missense mutations in Alagille syndrome. Human molecular genetics 69 11157803
2017 miR-598 inhibits metastasis in colorectal cancer by suppressing JAG1/Notch2 pathway stimulating EMT. Experimental cell research 67 28161537
2019 Long noncoding RNA DANCR contributes to docetaxel resistance in prostate cancer through targeting the miR-34a-5p/JAG1 pathway. OncoTargets and therapy 58 31371987
2017 Long non-coding RNA MALAT1 interacts with miR-124 and modulates tongue cancer growth by targeting JAG1. Oncology reports 58 28260102
2016 Anticancer Effect of Thymol on AGS Human Gastric Carcinoma Cells. Journal of microbiology and biotechnology 58 26437948
2017 The NOTCH Ligand JAG1 Regulates GDNF Expression in Sertoli Cells. Stem cells and development 57 28051360
2011 Plasminogen activator uPA is a direct transcriptional target of the JAG1-Notch receptor signaling pathway in breast cancer. Cancer research 56 21199807
2020 Jag1 Modulates an Oscillatory Dll1-Notch-Hes1 Signaling Module to Coordinate Growth and Fate of Pancreatic Progenitors. Developmental cell 54 32059775
2009 KSHV manipulates Notch signaling by DLL4 and JAG1 to alter cell cycle genes in lymphatic endothelia. PLoS pathogens 51 19816565
2001 Mutation analysis of Jagged1 (JAG1) in Alagille syndrome patients. Human mutation 50 11180599
1997 Identification and cloning of the human homolog (JAG1) of the rat Jagged1 gene from the Alagille syndrome critical region at 20p12. Genomics 50 9268641
2008 Aicardi-Goutières syndrome (AGS). European journal of paediatric neurology : EJPN : official journal of the European Paediatric Neurology Society 43 18343173
2014 Quercetin induces apoptosis by inhibiting MAPKs and TRPM7 channels in AGS cells. International journal of molecular medicine 42 24647664
2003 Conditional JAG1 mutation shows the developing heart is more sensitive than developing liver to JAG1 dosage. American journal of human genetics 41 12649809
1978 Genetics and ontogeny of aldehyde dehydrogenase isozymes in the mouse: localization of Ahd-1 encoding the mitochondrial isozyme on chromosome 4. Biochemical genetics 41 751648
2015 Human Cytomegalovirus Infection Dysregulates the Localization and Stability of NICD1 and Jag1 in Neural Progenitor Cells. Journal of virology 40 25903338
1981 Genetics of aldehyde dehydrogenase isozymes in the mouse: evidence for multiple loci and localization of Ahd-2 on chromosome 19. Genetics 40 7274657
2020 Assessing the impact of AGS-004, a dendritic cell-based immunotherapy, and vorinostat on persistent HIV-1 Infection. Scientific reports 38 32198428
2017 miR-181a modulates proliferation, migration and autophagy in AGS gastric cancer cells and downregulates MTMR3. Molecular medicine reports 37 28447759
2022 Current and Future Strategies for the Diagnosis and Treatment of the Alpha-Gal Syndrome (AGS). Journal of asthma and allergy 36 35879928
2020 Depletion of circ_0007841 inhibits multiple myeloma development and BTZ resistance via miR-129-5p/JAG1 axis. Cell cycle (Georgetown, Tex.) 36 33131409
2002 EBV-expressing AGS gastric carcinoma cell sublines present increased motility and invasiveness. International journal of cancer 34 12115496
1981 Genetics of the Akp-2 locus for alkaline phosphatase of liver, kidney, bone, and placenta in the mouse. Linkage with the Ahd-1 locus on chromosome 4. The Journal of heredity 34 7334202
2022 HOXA-AS2 contributes to regulatory T cell proliferation and immune tolerance in glioma through the miR-302a/KDM2A/JAG1 axis. Cell death & disease 33 35181676
2016 MiR-199b-5p inhibits osteogenic differentiation in ligamentum flavum cells by targeting JAG1 and modulating the Notch signalling pathway. Journal of cellular and molecular medicine 33 27957826
2013 Berberine counteracts enhanced IL-8 expression of AGS cells induced by evodiamine. Life sciences 33 24063987
2016 Claudin-6 enhances cell invasiveness through claudin-1 in AGS human adenocarcinoma gastric cancer cells. Experimental cell research 32 27914788
2004 AGS proteins, GPR motifs and the signals processed by heterotrimeric G proteins. Biology of the cell 32 15207906
2014 NOTCH ligands JAG1 and JAG2 as critical pro-survival factors in childhood medulloblastoma. Acta neuropathologica communications 31 24708907
2012 Upregulated JAG1 enhances cell proliferation in adrenocortical carcinoma. Clinical cancer research : an official journal of the American Association for Cancer Research 30 22427350
2019 Kras/ADAM17-Dependent Jag1-ICD Reverse Signaling Sustains Colorectal Cancer Progression and Chemoresistance. Cancer research 29 31506332
2019 Coronary arterial development is regulated by a Dll4-Jag1-EphrinB2 signaling cascade. eLife 29 31789590
2017 E-cadherin expression increases cell proliferation by regulating energy metabolism through nuclear factor-κB in AGS cells. Cancer science 29 28699254
2012 Requirements for Jag1-Rbpj mediated Notch signaling during early mouse lens development. Developmental dynamics : an official publication of the American Association of Anatomists 29 22275127
2024 Hypermethylation leads to the loss of HOXA5, resulting in JAG1 expression and NOTCH signaling contributing to kidney fibrosis. Kidney international 28 38521405
2022 JAG1-NOTCH4 mechanosensing drives atherosclerosis. Science advances 28 36044575
2020 GATA1-regulated JAG1 promotes ovarian cancer progression by activating Notch signal pathway. Protoplasma 28 31897811
2024 Soluble and multivalent Jag1 DNA origami nanopatterns activate Notch without pulling force. Nature communications 27 38238313
2024 Jaceosidin induces apoptosis and inhibits migration in AGS gastric cancer cells by regulating ROS-mediated signaling pathways. Redox report : communications in free radical research 27 38318818
2022 p-Coumaric acid, Kaempferol, Astragalin and Tiliroside Influence the Expression of Glycoforms in AGS Gastric Cancer Cells. International journal of molecular sciences 26 35955735
2020 Highly Expressed DLL4 and JAG1: Their Role in Incidence of Breast Cancer Metastasis. Archives of medical research 26 32111499
2020 Vortioxetine induces apoptosis and autophagy of gastric cancer AGS cells via the PI3K/AKT pathway. FEBS open bio 26 32750222
2019 AGS-30, an andrographolide derivative, suppresses tumor angiogenesis and growth in vitro and in vivo. Biochemical pharmacology 26 31706845
2015 Dihydromyricetin induces cell apoptosis via a p53-related pathway in AGS human gastric cancer cells. Genetics and molecular research : GMR 26 26634523
2000 Jagged1 (JAG1) mutation detection in an Australian Alagille syndrome population. Human mutation 26 11058898
2020 Naringin Induces Lysosomal Permeabilization and Autophagy Cell Death in AGS Gastric Cancer Cells. The American journal of Chinese medicine 25 32329644
2016 JAG1-Mediated Notch Signaling Regulates Secretory Cell Differentiation of the Human Airway Epithelium. Stem cell reviews and reports 25 27216293
2015 JAG1 Mutation Spectrum and Origin in Chinese Children with Clinical Features of Alagille Syndrome. PloS one 25 26076142
2019 Evolutionary modification of AGS protein contributes to formation of micromeres in sea urchins. Nature communications 24 31439829
2010 Isolation, identification and characterization of a new lipolytic pseudomonas sp., strain AHD-1, from Tunisian soil. Environmental technology 24 20232682
2017 In vivo and in vitro effects of microRNA-124 on human gastric cancer by targeting JAG1 through the Notch signaling pathway. Journal of cellular biochemistry 23 28941308
2021 Nestin+/CD31+ cells in the hypoxic perivascular niche regulate glioblastoma chemoresistance by upregulating JAG1 and DLL4. Neuro-oncology 22 33249476
2017 Soluble OX40L and JAG1 Induce Selective Proliferation of Functional Regulatory T-Cells Independent of canonical TCR signaling. Scientific reports 22 28045060
2015 Minor histocompatibility Ags: identification strategies, clinical results and translational perspectives. Bone marrow transplantation 22 26501766
2014 Spectrum of JAG1 gene mutations in Polish patients with Alagille syndrome. Journal of applied genetics 22 24748328
2024 The IGF2BP3/Notch/Jag1 pathway: A key regulator of hepatic stellate cell ferroptosis in liver fibrosis. Clinical and translational medicine 21 39113232
2019 MicroRNA-539 inhibits the progression of Wilms' Tumor through downregulation of JAG1 and Notch1/3. Cancer biomarkers : section A of Disease markers 21 30530967
2018 MicroRNA-30d/JAG1 axis modulates pulmonary fibrosis through Notch signaling pathway. Pathology, research and practice 21 30029934
2017 Efficiency and cytotoxicity analysis of cationic lipids-mediated gene transfection into AGS gastric cancer cells. Artificial cells, nanomedicine, and biotechnology 21 28728449
2017 Overexpression of FOXA1 inhibits cell proliferation and EMT of human gastric cancer AGS cells. Gene 21 29129808
2018 JAG1 overexpression contributes to Notch1 signaling and the migration of HTLV-1-transformed ATL cells. Journal of hematology & oncology 20 30231940
2006 Non-receptor activators of heterotrimeric G-protein signaling (AGS proteins). Seminars in cell & developmental biology 19 16621626
2022 Engineered patterns of Notch ligands Jag1 and Dll4 elicit differential spatial control of endothelial sprouting. iScience 18 35602952
2019 Activation of Notch Signaling by Oocytes and Jag1 in Mouse Ovarian Granulosa Cells. Endocrinology 18 31609444
2018 MiR-199b represses porcine muscle satellite cells proliferation by targeting JAG1. Gene 18 30599234
2022 The oncogenic JAG1 intracellular domain is a transcriptional cofactor that acts in concert with DDX17/SMAD3/TGIF2. Cell reports 17 36417870
2020 miR-199b-5p promoted chondrogenic differentiation of C3H10T1/2 cells by regulating JAG1. Journal of tissue engineering and regenerative medicine 17 32870569
2011 JAG1 and COL1A1 polymorphisms and haplotypes in relation to bone mineral density variations in postmenopausal Mexican-Mestizo Women. Age (Dordrecht, Netherlands) 17 22174012
2023 Exosomes from hypoxia-conditioned apical papilla stem cells accelerate angiogenesis in vitro through Notch/JAG1/VEGF signaling. Tissue & cell 16 37595532
2021 Circulating PTGS2, JAG1, GUCY2C and PGF mRNA in Peripheral Blood and Serum as Potential Biomarkers for Patients with Metastatic Colon Cancer. Journal of clinical medicine 16 34067294
2016 Expression of α-fetoprotein in gastric cancer AGS cells contributes to invasion and metastasis by influencing anoikis sensitivity. Oncology reports 16 26986949
2023 Jag1-Notch cis-interaction determines cell fate segregation in pancreatic development. Nature communications 15 36681690
2022 Assemblies of JAG1 and JAG2 determine tracheobronchial cell fate in mucosecretory lung disease. JCI insight 15 35819850
2015 Alagille syndrome and a JAG1 mutation: 41 cases of experience at a single center. Korean journal of pediatrics 15 26576184
2012 Cytotoxicity of methylsulfonylmethane on gastrointestinal (AGS, HepG2, and KEYSE-30) cancer cell lines. Journal of gastrointestinal cancer 15 21626237
2005 Twelve novel JAG1 gene mutations in Polish Alagille syndrome patients. Human mutation 15 15712272
2022 LINC00173 regulates polycystic ovarian syndrome progression by promoting apoptosis and repressing proliferation in ovarian granulosa cells via the microRNA-124-3p (miR-124-3p)/jagged canonical Notch ligand 1 (JAG1) pathway. Bioengineered 14 35441583
2020 MicroRNA-489-3p Represses Hepatic Stellate Cells Activation by Negatively Regulating the JAG1/Notch3 Signaling Pathway. Digestive diseases and sciences 14 32144602
2020 Ag@S-nitrosothiol core-shell nanoparticles for chemo and photothermal synergistic tumor targeted therapy. Journal of materials chemistry. B 14 32475994
2019 Downregulation of AKT and MDM2, Melatonin Induces Apoptosis in AGS and MGC803 Cells. Anatomical record (Hoboken, N.J. : 2007) 14 30809951
2019 miR-449a regulates insulin signalling by targeting the Notch ligand, Jag1 in skeletal muscle cells. Cell communication and signaling : CCS 14 31345231
2018 Lentivirus-mediated overexpression of miR-124 suppresses growth and invasion by targeting JAG1 and EZH2 in gastric cancer. Oncology letters 14 29731896
2017 miR‑140‑5p inhibits human glioma cell growth and invasion by targeting JAG1. Molecular medicine reports 14 28713992
2012 SNX17 regulates Notch pathway and pancreas development through the retromer-dependent recycling of Jag1. Cell regeneration (London, England) 14 25408867
2023 Efficacy and safety of baricitinib in Japanese patients with autoinflammatory type I interferonopathies (NNS/CANDLE, SAVI, And AGS). Pediatric rheumatology online journal 13 37087470
2022 DNA repair proteins as the targets for paroxetine to induce cytotoxicity in gastric cancer cell AGS. American journal of cancer research 13 35530295