Affinage

JAG1

Protein jagged-1 · UniProt P78504

Length
1218 aa
Mass
133.8 kDa
Annotated
2026-06-10
100 papers in source corpus 25 papers cited in narrative 25 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

JAG1 is a transmembrane Notch pathway ligand that activates Notch receptors on adjacent cells to control cell-fate decisions across diverse tissues including pancreas, ovary, testis, heart, vasculature, and epidermis (PMID:32059775, PMID:31609444, PMID:28051360, PMID:31789590, PMID:33891780). Productive trans-activation depends on events in the signal-sending cell: ubiquitylation by Mind bomb is required for Jag1 to activate Notch (PMID:20573700), and SNX17/retromer-dependent endocytic recycling maintains surface Jag1 levels to sustain signaling (PMID:25408867); multivalent Jag1 presentation is sufficient to activate Notch even in the absence of mechanical pulling force (PMID:38238313). Through this axis JAG1 engages NOTCH1, NOTCH2, and NOTCH4 receptors and drives canonical HES1/HEY1 target induction that governs context-specific outcomes—repressing GDNF in a Sertoli-cell feedback loop limiting spermatogonial self-renewal (PMID:28051360), restraining and then specifying pancreatic progenitor fate via modulation of oscillating Hes1, with parallel cell-autonomous cis-inhibition driving exit from multipotency (PMID:32059775, PMID:36681690), and acting as a pro-atherogenic mechanosensor at sites of disturbed flow in antagonism with Dll4 during coronary morphogenesis (PMID:36044575, PMID:31789590). Independently of trans-Notch signaling, the JAG1 intracellular domain is liberated by ADAM17/γ-secretase processing and translocates to the nucleus, where as JICD1 it partners with DDX17, SMAD3, and TGIF2 to induce SOX2 and drive oncogenic transformation, EMT, and therapy resistance (PMID:31506332, PMID:36417870). Disease-causing missense mutations disrupt JAG1 glycosylation and cell-surface trafficking, causing ER retention and loss of signaling, establishing haploinsufficiency and defective intracellular transport as the basis of Alagille syndrome and associated cardiac defects (PMID:11157803, PMID:12649809, PMID:9585603). JAG1 expression is itself tightly controlled, being directly repressed by HOXA5 and induced by ATF4 (PMID:38521405, PMID:35401837).

Mechanistic history

Synthesis pass · year-by-year structured walk · 19 steps
  1. 1998 Medium

    Established the genetic basis of Alagille syndrome by showing that whole-gene deletion phenocopies intragenic truncations, defining JAG1 haploinsufficiency as the disease mechanism.

    Evidence SSCP mutation screening and FISH deletion analysis with genotype-phenotype correlation across 54 AGS families

    PMID:9585603

    Open questions at the time
    • Mechanism inferred from deletion=truncation equivalence rather than biochemical reconstitution
    • Does not explain the basis of organ-specific phenotypic variability
  2. 2001 High

    Resolved how missense mutations cause disease by demonstrating that pathogenic variants abolish glycosylation and surface delivery, retaining JAG1 intracellularly and ablating Notch signaling, distinguishing true mutations from polymorphisms.

    Evidence Cell-surface localization, glycosylation analysis, and Notch reporter assays with site-directed mutagenesis

    PMID:11157803

    Open questions at the time
    • Did not identify the trafficking machinery responsible for ER retention
    • Does not address dosage thresholds across tissues
  3. 2003 High

    Explained organ-specific sensitivity by showing a temperature-sensitive missense allele yields mixed functional/non-functional protein populations and that the heart tolerates reduced JAG1 dosage less than the liver.

    Evidence Cell fractionation, glycosylation, temperature-shift, and signaling assays in a cardiac-phenotype family

    PMID:12649809

    Open questions at the time
    • Molecular basis of tissue-specific dosage sensitivity not defined
    • Modifier genes not identified
  4. 2010 High

    Identified Mind bomb ubiquitylation of Jag1 in signal-sending cells as a required step for ligand-dependent Notch activation, linking ligand endocytosis to signaling competence and to notochord cell-fate decisions.

    Evidence Zebrafish loss/gain-of-function genetics, ubiquitylation assay, and in vivo imaging

    PMID:20573700

    Open questions at the time
    • Ubiquitylation site mapping not defined
    • Did not address how ubiquitylation couples to endocytic pulling force
  5. 2012 Medium

    Defined the trafficking pathway that sustains ligand signaling, showing SNX17 binds Jag1 and drives retromer-dependent recycling to the surface to maintain Notch-activating ligand levels.

    Evidence Co-IP, zebrafish knockdown, cell-surface protein assays, and genetic epistasis

    PMID:25408867

    Open questions at the time
    • Single-lab Co-IP without reciprocal structural validation
    • Recycling kinetics and human relevance not established
  6. 2012 Medium

    Showed JAG1 acts in a juxtacrine manner to drive proliferation through canonical Notch signaling in adrenocortical carcinoma, an early demonstration of its oncogenic trans-activating role.

    Evidence shRNA knockdown, co-culture proliferation assay, Notch reporter, immunoblot

    PMID:22427350

    Open questions at the time
    • Receptor identity not specified
    • Downstream target genes not mapped
  7. 2014 Medium

    Extended JAG1's pro-tumor role across cancer types, linking it to NOTCH2/HES1 survival signaling in medulloblastoma and to a NOTCH1/osteopontin metastatic cascade dependent on membrane localization in HCC.

    Evidence shRNA/RNAi knockdown, Notch reporter and HES1 readout in MB lines; tissue microarray localization and OPN measurement in HCC

    PMID:24708907 PMID:25176314

    Open questions at the time
    • Causality between membrane localization and metastasis correlative
    • Receptor selectivity mechanism unclear
  8. 2017 High

    Revealed a tissue feedback circuit in which spermatogonial JAG1 activates Sertoli-cell Notch, whose targets HES1/HEY1 directly repress Gdnf to limit stem-cell self-renewal.

    Evidence Double-mutant mice, dual luciferase, ChIP-qPCR, and co-culture

    PMID:28051360

    Open questions at the time
    • Quantitative contribution to germline homeostasis in vivo not measured
  9. 2019 High

    Uncovered a non-canonical reverse-signaling mechanism: KRAS/ERK/ADAM17 cleaves Jagged1 to release a nuclear Jag1-ICD that drives tumor growth, EMT, and chemoresistance independent of trans-Notch activation.

    Evidence In vitro cleavage assays, nuclear fractionation, gain/loss-of-function, xenografts, and ADAM17 inhibition

    PMID:31506332

    Open questions at the time
    • Nuclear partners of Jag1-ICD not identified in this study
    • Direct transcriptional targets not mapped
  10. 2019 High

    Defined antagonistic ligand functions in vascular morphogenesis, with endocardial Jag1 required for capillary sprouting opposing Dll4, converging on EphrinB2 as a downstream effector.

    Evidence Conditional Jag1/Dll4 KO mice, Mfng forced expression, explant rescue, and human EC experiments

    PMID:31789590

    Open questions at the time
    • Mechanism of Fringe-dependent ligand discrimination not fully resolved
  11. 2019 High

    Established an oocyte-to-somatic signaling role for JAG1 in the ovary, where germ-cell-expressed JAG1 activates Notch in granulosa cells.

    Evidence Notch reporter mice, germ cell ablation, KitWv/Wv mice, oocyte-specific Jag1 KO, and recombinant JAG1 rescue

    PMID:31609444

    Open questions at the time
    • Receptor and downstream granulosa targets not detailed
  12. 2020 High

    Dissected dual roles in pancreatic development, showing Jag1 restrains progenitor growth and, upon segregation to pro-acinar cells, is required for bipotent progenitor specification by modulating oscillating Hes1.

    Evidence Conditional Jag1 KO, Jag1;Dll1 double mutants, Hes1 oscillation imaging, and lineage tracing

    PMID:32059775

    Open questions at the time
    • How Jag1 expression segregation is controlled not defined
  13. 2022 High

    Identified the nuclear cofactor complex through which the JAG1 intracellular domain drives transformation, showing JICD1 binds DDX17/SMAD3/TGIF2 to induce SOX2 and confer cancer-stem-cell properties.

    Evidence ChIP-seq, proteomics, transcriptomics, gain-of-function, and SOX2 rescue

    PMID:36417870

    Open questions at the time
    • Stoichiometry and structure of the JICD1 complex unresolved
    • Generality beyond astrocyte transformation untested
  14. 2022 High

    Established JAG1 as a pro-atherogenic endothelial mechanosensor, with disturbed flow activating JAG1-NOTCH4 and suppressing proliferative/migratory EC subsets.

    Evidence EC-specific Jag1 KO mice, multi-species artery models, human EC culture, light-sheet imaging, scRNA-seq

    PMID:36044575

    Open questions at the time
    • Direct mechanotransduction step linking flow to JAG1 not defined
  15. 2022 Medium

    Showed γ-secretase processing generates distinct JAG1/JAG2 molecular assemblies that tune Notch signal strength and goblet versus ciliated cell fate in airway epithelium.

    Evidence GSC inhibition, neutralizing peptides/antibodies, fractionation, RNA-Seq in air-liquid-interface cultures

    PMID:35819850

    Open questions at the time
    • Identity and function of the C-terminal peptide product unclear
    • Single-lab pharmacologic perturbations
  16. 2022 High

    Mapped upstream regulation of JAG1 expression in distinct contexts: ATF4 directly transactivates JAG1 to remodel the leukemic vascular niche, and FAS-ERK signaling controls JAG1 in a linear FAS-ERK-JAG1-NOTCH1 oncogenic cascade.

    Evidence ChIP (ATF4 on JAG1), EC-specific PERK KO mice, SEV studies in T-ALL; FAS KO, phosphoprotein arrays, NOTCH1-ICD rescue in OSCC

    PMID:35249111 PMID:35401837

    Open questions at the time
    • Cross-talk between transcriptional regulators of JAG1 not integrated
  17. 2023 Medium

    Distinguished cis from trans Jag1 functions in pancreatic fate, with cis-inhibition of Notch driving multipotency exit and trans-interaction required for bipotent fate.

    Evidence Mathematical modeling validated against Jag1/Dll1 KO mice and small-molecule Notch inhibitors

    PMID:36681690

    Open questions at the time
    • Model-based inference limits mechanistic confidence
    • Molecular basis of cis versus trans engagement not biochemically resolved
  18. 2024 High

    Demonstrated that prolonged multivalent ligand binding is sufficient for Notch activation, decoupling JAG1-driven signaling from mechanical pulling force.

    Evidence DNA origami nanopattern display of soluble Jag1 with chimeric ligand controls and Notch reporters

    PMID:38238313

    Open questions at the time
    • Relationship between force-independent and endocytosis-dependent activation in vivo unresolved
  19. 2024 High

    Defined post-transcriptional and transcriptional control of JAG1 in fibrosis: HOXA5 directly represses JAG1 (lost via DNA methylation in kidney fibrosis), and the m6A reader IGF2BP3 stabilizes Jag1 mRNA to sustain Hes1/GPX4 and suppress hepatic stellate cell ferroptosis.

    Evidence ChIP and conditional KO/knockin mice with 5-Aza (HOXA5 axis); IGF2BP3 KO mice with m6A multi-omics and ferroptosis assays (HSC axis)

    PMID:38521405 PMID:39113232

    Open questions at the time
    • Integration of methylation, m6A, and transcription factor inputs on JAG1 unresolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the distinct JAG1 modes—force-dependent trans-activation, force-independent multivalent activation, cis-inhibition, and nuclear JICD1 reverse signaling—are coordinately selected within a single cell remains unresolved.
  • No unified model integrating trafficking, cleavage, and receptor engagement modes
  • Structural basis of JICD1 cofactor complex unknown
  • Determinants of receptor (NOTCH1/2/4) selectivity undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0048018 receptor ligand activity 4 GO:0140110 transcription regulator activity 2 GO:0140299 molecular sensor activity 1
Localization
GO:0005886 plasma membrane 4 GO:0005634 nucleus 2 GO:0005783 endoplasmic reticulum 2
Pathway
R-HSA-162582 Signal Transduction 4 R-HSA-1643685 Disease 4 R-HSA-1266738 Developmental Biology 3 R-HSA-74160 Gene expression (Transcription) 3
Partners
DDX17MIB1NOTCH1NOTCH2NOTCH4SMAD3SNX17TGIF2
Complex memberships
JICD1-DDX17-SMAD3-TGIF2 transcriptional complex

Evidence

Reading pass · 25 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2001 JAG1 missense mutations R184H and L37S cause loss of Notch signaling activity, abnormal glycosylation, failure to reach the cell surface, and intracellular accumulation (likely in the ER), establishing defective intracellular transport as a disease mechanism in Alagille syndrome. Missense mutations P163L and P871R showed normal cell-surface localization and normal Notch signaling, consistent with polymorphisms rather than pathogenic mutations. Cell-surface localization assays, glycosylation analysis, Notch signaling reporter assays, site-directed mutagenesis Human molecular genetics High 11157803
2003 The JAG1-G274D missense mutation produces two protein populations: one abnormally glycosylated and retained intracellularly (non-functional), and one normally glycosylated and surface-localized (functional). The mutation is temperature-sensitive, producing more non-functional protein at higher temperatures. Carriers have >50% but <100% normal JAG1 surface levels. The cardiac-specific phenotype of this family indicates that the developing heart is more sensitive than the developing liver to reduced JAG1 dosage. Cell fractionation, glycosylation analysis, cell-surface localization, temperature-shift experiments, Notch signaling assay American journal of human genetics High 12649809
1998 JAG1 mutations (deletions, truncations, and missense) cause Alagille syndrome primarily through haploinsufficiency, as deletion of the entire gene produces the same phenotype as intragenic truncating mutations. Two missense mutations at the same amino acid residue suggest that mechanisms beyond haploinsufficiency may also exist. SSCP mutation screening, FISH gene deletion analysis, phenotype-genotype correlation in 54 AGS patients/families American journal of human genetics Medium 9585603
2010 Mind bomb (Mib) ubiquitylates Jagged1 (Jag1) and is required in signal-sending cells for Jag1 to activate Notch signaling. In zebrafish, Mib-Jag1-Notch signaling governs cell-fate decisions between vacuolated and non-vacuolated notochord cells, affecting peri-notochordal basement membrane formation. Zebrafish loss-of-function and gain-of-function genetics, ubiquitylation assay, in vivo imaging Development (Cambridge, England) High 20573700
2010 JAG1 missense mutations associated with right-sided cardiac defects (TOF, PS) display heterogeneous effects on protein localization, post-translational modification, and Notch signaling activation, with some behaving as complete haploinsufficiency alleles, indicating that additional tissue-specific modifiers influence organ-specific phenotypes. Protein localization assays, post-translational modification analysis, Notch signaling reporter assay in patient-derived missense mutants Human mutation Medium 20437614
2012 JAG1 is upregulated in adrenocortical carcinoma (ACC) and enhances cell proliferation through activation of canonical Notch signaling in a non-cell-autonomous (juxtacrine) manner; JAG1 knockdown and inhibition of post-receptor Notch signaling (DNMaml) both reduce proliferation equivalently. Jag1 shRNA knockdown, co-culture FACS proliferation assay, luciferase Notch reporter, immunoblot, QPCR Clinical cancer research Medium 22427350
2017 In Sertoli cells, JAG1 expressed on the surface of spermatogonial stem/progenitor cells activates canonical NOTCH signaling in Sertoli cells; NOTCH targets HES1 and HEY1 directly bind the Gdnf promoter and repress GDNF expression, establishing a negative feedback loop that limits stem cell 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, KRAS/ERK/ADAM17 signaling drives constitutive cleavage of Jagged1, releasing the intracellular domain (Jag1-ICD), which translocates to the nucleus and drives tumor growth, EMT, and chemoresistance via a non-canonical reverse signaling mechanism independent of trans-Notch activation. In vitro cleavage assays, nuclear fractionation, gain/loss-of-function experiments in vitro and xenograft models, pharmacologic ADAM17 inhibition Cancer research High 31506332
2022 The JAG1 intracellular domain (JICD1), generated by proteolytic processing analogous to NOTCH1, acts as a transcriptional cofactor by forming a complex with DDX17, SMAD3, and TGIF2, increasing SOX2 expression and driving astrocyte transformation toward cancer stem cell properties (tumor formation, invasiveness, stemness, therapy resistance). Transcriptome analysis, ChIP-seq, proteomics, gain-of-function, SOX2 rescue experiments 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. Single-cell RNA sequencing shows Jag1 suppresses proliferating/migrating EC subsets, establishing JAG1 as a pro-atherogenic mechanosensor. EC-specific Jag1 knockout mice, porcine/murine artery models, human coronary artery EC culture, light-sheet imaging, scRNA-seq Science advances High 36044575
2019 Jag1 and Dll4 exert antagonistic roles in coronary arterial development: endocardial Jag1 removal blocks sinus venosus capillary sprouting (primary plexus formation), while Dll4 inactivation stimulates excessive capillary growth. EphrinB2 is a critical downstream effector of the antagonistic Dll4-Jag1 functions in arterial morphogenesis, epistatic rescue experiments confirming this cascade. Conditional endocardial Jag1 and Dll4 knockout mice, Mfng forced expression, ventricular explant angiogenic rescue, primary human EC experiments eLife High 31789590
2020 Jag1, uniformly expressed in multipotent pancreatic progenitors (MPCs), restrains MPC growth. When Jag1 expression later segregates to pro-acinar cells, it becomes critical for bipotent progenitor specification; Jag1;Dll1 double mutants lose all bipotent progenitors. Jag1 modulates oscillating Hes1 activity to coordinate MPC growth and fate. Conditional Jag1 knockout mice, Jag1;Dll1 double mutants, Hes1 oscillation imaging, lineage tracing Developmental cell High 32059775
2012 SNX17 binds Jag1a and promotes retromer-dependent recycling of Jag1a to the plasma membrane in ligand-expressing cells, thereby maintaining Jag1a protein levels at the cell surface and enabling Notch signaling activation; inhibition of this pathway impairs neurogenesis and pancreas development in zebrafish. Co-IP, zebrafish knockdown, cell-surface protein assays, genetic epistasis in zebrafish Cell regeneration Medium 25408867
2014 JAG1 mediates pro-proliferative and pro-survival signaling in medulloblastoma via activation of NOTCH2 receptor and induction of HES1 expression; JAG1 knockdown reduces MB cell survival. shRNA knockdown, Notch signaling reporter, HES1 expression analysis in MB cell lines and primary tumor cohorts Acta neuropathologica communications Medium 24708907
2022 In the tracheobronchial epithelium, JAG1 undergoes posttranslational processing by the γ-secretase complex (GSC) generating a C-terminal peptide, and GSC also regulates abundance of full-length JAG2 at the cell surface. These PTMs create distinct JAG1/JAG2 assemblies that regulate Notch signal strength and determine goblet vs. ciliated cell fate via a WNT-independent mechanism. GSC inhibitor treatment, neutralizing peptides/antibodies, biochemical fractionation, RNA-Seq, WNT agonist/antagonist studies in human air-liquid-interface cultures JCI insight Medium 35819850
2024 HOXA5 directly binds the JAG1 gene promoter and represses its transcription; loss of HOXA5 via DNA methylation in kidney fibrosis de-represses JAG1, activating JAG1-NOTCH signaling and promoting fibrogenesis. Conditional Hoxa5 KO aggravates fibrosis; conditional Hoxa5 knockin suppresses it. ChIP (HOXA5 on Jag1 promoter), conditional KO and knockin mice, 5-Aza treatment, genome-wide methylation analysis Kidney international High 38521405
2022 In T-ALL, leukemia-derived small extracellular vesicles activate PERK-eIF2a-ATF4 signaling in bone marrow endothelial cells; ATF4 directly upregulates JAG1 transcription (confirmed by ChIP), remodeling the vascular niche. EC-specific PERK deletion abolishes aberrant JAG1 upregulation, improves HSC maintenance, and improves leukemia survival. ChIP (ATF4 on JAG1), EC-specific PERK knockout mice, small extracellular vesicle characterization, transcriptomic analysis, xenograft models Theranostics High 35401837
2024 Soluble, multivalent Jag1 presented on DNA origami nanostructures activates Notch signaling in neuroepithelial stem-like cells without requiring a pulling force, demonstrating that prolonged multivalent Jag1 binding is sufficient for Notch activation in the absence of mechanical force. DNA origami nanopattern display of Jag1, Notch signaling reporter assays, chimeric ligand controls ruling out confounders Nature communications High 38238313
2019 Oocyte-expressed JAG1 activates Notch signaling in ovarian granulosa cells: germ cell ablation or oocyte-specific Jag1 deletion suppresses Notch activation in granulosa cells, and recombinant JAG1 enhances Notch target gene expression in granulosa cells in vitro. Transgenic Notch reporter mice, busulfan germ cell ablation, KitWv/Wv mice, oocyte-specific Jag1 conditional KO, recombinant JAG1 treatment of granulosa cells Endocrinology High 31609444
2018 In ATL cells, JAG1 overexpression is driven by the HTLV-1 viral protein Tax and cellular factors miR-124a, STAT3, and NFATc1. Blockade of JAG1 signaling by shRNA knockdown or neutralizing antibodies dampens Notch1 downstream signaling and limits cell migration of ATL cells. RT-PCR, FACS, IHC, shRNA knockdown, neutralizing antibodies, Notch signaling analysis Journal of hematology & oncology Medium 30231940
2014 JAG1 membrane localization (but not cytoplasmic localization) in HCC is associated with extrahepatic metastasis and correlates with Notch1 membrane localization; JAG1 or Notch1 knockdown reduces osteopontin (OPN) expression in HCC cells, placing JAG1/Notch1/OPN in a functional cascade regulating metastasis. Tissue microarray localization (112 tumors), RNA interference of JAG1 and Notch1, OPN expression measurement International journal of oncology Medium 25176314
2021 JAG1 in normal epidermal cells activates Notch1 in senescent cells and is required for their removal from the basal layer; JAG1 knockdown in normal cells or Notch signaling inhibition suppresses preferential removal of senescent cells from the basal layer in 3D reconstructed epidermis. 3D reconstructed epidermis with mixed normal and UVB-senescent cells, JAG1 siRNA knockdown, Notch inhibitor treatment, FACS and microscopy Experimental dermatology Medium 33891780
2022 FAS receptor controls JAG1 expression and NOTCH pathway activity through ERK phosphorylation in OSCC cells; FAS ligand or recombinant JAG1 protein treatment increases NOTCH activity, and this is abolished by FAS receptor knockout. NOTCH1 intracellular domain rescues spheroid formation in FAS KO cells, placing FAS-ERK-JAG1-NOTCH1 in a linear cascade. FAS receptor knockout, cDNA microarray, phosphoprotein arrays, NOTCH1-ICD rescue, pharmacologic ERK inhibition, in vivo xenograft Cell death discovery Medium 35249111
2023 Jag1-mediated cis-inhibition of Notch receptors in multipotent pancreatic progenitors is a cell-autonomous mechanism that drives exit from the multipotent state; a mathematical model validated against Jag1 and Dll1 KO mice and small molecule Notch inhibitors shows cis-interaction is required for MPC differentiation while trans-interaction is required for bipotent fate adoption. Mathematical modeling validated against conditional KO mice (Jag1, Dll1), small molecule Notch pathway inhibitors, comparison with published mutant phenotypes Nature communications Medium 36681690
2024 IGF2BP3 (an m6A reader) binds and stabilizes Jag1 mRNA; IGF2BP3 knockout reduces m6A content and expression of Jag1 and downstream Hes1 in hepatic stellate cells, decreasing GPX4 and promoting HSC ferroptosis to reduce liver fibrosis. IGF2BP3 KO mice (HSC-specific), m6A multi-omics, Hes1/GPX4 measurement, ferroptosis assays Clinical and translational medicine Medium 39113232

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
2006 Jagged1 (JAG1) mutations in Alagille syndrome: increasing the mutation detection rate. Human mutation 142 16575836
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 113 31343788
1990 Characterization and strain distribution pattern of the murine Ah receptor specified by the Ahd and Ahb-3 alleles. Molecular pharmacology 105 2169579
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) 95 27678529
2010 Jagged1 (JAG1) mutations in patients with tetralogy of Fallot or pulmonic stenosis. Human mutation 93 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
2021 The effect of paclitaxel on apoptosis, autophagy and mitotic catastrophe in AGS cells. Scientific reports 74 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
2017 The NOTCH Ligand JAG1 Regulates GDNF Expression in Sertoli Cells. Stem cells and development 58 28051360
2017 Long non-coding RNA MALAT1 interacts with miR-124 and modulates tongue cancer growth by targeting JAG1. Oncology reports 58 28260102
2020 Jag1 Modulates an Oscillatory Dll1-Notch-Hes1 Signaling Module to Coordinate Growth and Fate of Pancreatic Progenitors. Developmental cell 57 32059775
2001 Mutation analysis of Jagged1 (JAG1) in Alagille syndrome patients. Human mutation 50 11180599
2021 Exosomes derived from microRNA-512-5p-transfected bone mesenchymal stem cells inhibit glioblastoma progression by targeting JAG1. Aging 43 33795521
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
1981 Genetics of aldehyde dehydrogenase isozymes in the mouse: evidence for multiple loci and localization of Ahd-2 on chromosome 19. Genetics 40 7274657
2022 Current and Future Strategies for the Diagnosis and Treatment of the Alpha-Gal Syndrome (AGS). Journal of asthma and allergy 38 35879928
2020 Assessing the impact of AGS-004, a dendritic cell-based immunotherapy, and vorinostat on persistent HIV-1 Infection. Scientific reports 38 32198428
2020 Depletion of circ_0007841 inhibits multiple myeloma development and BTZ resistance via miR-129-5p/JAG1 axis. Cell cycle (Georgetown, Tex.) 37 33131409
2017 miR-181a modulates proliferation, migration and autophagy in AGS gastric cancer cells and downregulates MTMR3. Molecular medicine reports 37 28447759
1988 Genetics of ocular NAD+-dependent alcohol dehydrogenase and aldehyde dehydrogenase in the mouse: evidence for genetic identity with stomach isozymes and localization of Ahd-4 on chromosome 11 near trembler. Biochemical genetics 35 3408474
2022 HOXA-AS2 contributes to regulatory T cell proliferation and immune tolerance in glioma through the miR-302a/KDM2A/JAG1 axis. Cell death & disease 34 35181676
2002 EBV-expressing AGS gastric carcinoma cell sublines present increased motility and invasiveness. International journal of cancer 34 12115496
2016 Claudin-6 enhances cell invasiveness through claudin-1 in AGS human adenocarcinoma gastric cancer cells. Experimental cell research 33 27914788
2013 Berberine counteracts enhanced IL-8 expression of AGS cells induced by evodiamine. Life sciences 33 24063987
2004 AGS proteins, GPR motifs and the signals processed by heterotrimeric G proteins. Biology of the cell 32 15207906
2024 Hypermethylation leads to the loss of HOXA5, resulting in JAG1 expression and NOTCH signaling contributing to kidney fibrosis. Kidney international 31 38521405
2014 NOTCH ligands JAG1 and JAG2 as critical pro-survival factors in childhood medulloblastoma. Acta neuropathologica communications 31 24708907
2019 Kras/ADAM17-Dependent Jag1-ICD Reverse Signaling Sustains Colorectal Cancer Progression and Chemoresistance. Cancer research 30 31506332
2017 E-cadherin expression increases cell proliferation by regulating energy metabolism through nuclear factor-κB in AGS cells. Cancer science 30 28699254
2012 Upregulated JAG1 enhances cell proliferation in adrenocortical carcinoma. Clinical cancer research : an official journal of the American Association for Cancer Research 30 22427350
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 29 38318818
2022 JAG1-NOTCH4 mechanosensing drives atherosclerosis. Science advances 29 36044575
2019 Coronary arterial development is regulated by a Dll4-Jag1-EphrinB2 signaling cascade. eLife 29 31789590
2024 Soluble and multivalent Jag1 DNA origami nanopatterns activate Notch without pulling force. Nature communications 28 38238313
2020 GATA1-regulated JAG1 promotes ovarian cancer progression by activating Notch signal pathway. Protoplasma 28 31897811
2022 An AGS-associated mutation in ADAR1 catalytic domain results in early-onset and MDA5-dependent encephalopathy with IFN pathway activation in the brain. Journal of neuroinflammation 27 36457126
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
2022 JAG1 enhances angiogenesis in triple-negative breast cancer through promoting the secretion of exosomal lncRNA MALAT1. Genes & diseases 26 37492742
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
2020 Naringin Induces Lysosomal Permeabilization and Autophagy Cell Death in AGS Gastric Cancer Cells. The American journal of Chinese medicine 25 32329644
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
2022 Kaempferol Inhibits Hepatic Stellate Cell Activation by Regulating miR-26b-5p/Jag1 Axis and Notch Pathway. Frontiers in pharmacology 22 35721153
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
2022 FAS receptor regulates NOTCH activity through ERK-JAG1 axis activation and controls oral cancer stemness ability and pulmonary metastasis. Cell death discovery 19 35249111
2022 Engineered patterns of Notch ligands Jag1 and Dll4 elicit differential spatial control of endothelial sprouting. iScience 19 35602952
2018 Cell Cycle Arrest and Apoptosis Induction of Phloroacetophenone Glycosides and Caffeoylquinic Acid Derivatives in Gastric Adenocarcinoma (AGS) Cells. Anti-cancer agents in medicinal chemistry 19 29256356
2006 Non-receptor activators of heterotrimeric G-protein signaling (AGS proteins). Seminars in cell & developmental biology 19 16621626
2023 Efficacy and safety of baricitinib in Japanese patients with autoinflammatory type I interferonopathies (NNS/CANDLE, SAVI, And AGS). Pediatric rheumatology online journal 18 37087470
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
2023 Jag1-Notch cis-interaction determines cell fate segregation in pancreatic development. Nature communications 17 36681690
2022 The oncogenic JAG1 intracellular domain is a transcriptional cofactor that acts in concert with DDX17/SMAD3/TGIF2. Cell reports 17 36417870
2020 Functional and transcriptomic characterization of cisplatin-resistant AGS and MKN-28 gastric cancer cell lines. PloS one 17 31990955
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
2017 Osteosarcoma cell-intrinsic colony stimulating factor-1 receptor functions to promote tumor cell metastasis through JAG1 signaling. American journal of cancer research 16 28469954
2016 Expression of α-fetoprotein in gastric cancer AGS cells contributes to invasion and metastasis by influencing anoikis sensitivity. Oncology reports 16 26986949
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 15 35441583
2022 DNA repair proteins as the targets for paroxetine to induce cytotoxicity in gastric cancer cell AGS. American journal of cancer research 15 35530295
2022 Assemblies of JAG1 and JAG2 determine tracheobronchial cell fate in mucosecretory lung disease. JCI insight 15 35819850
2020 MicroRNA-489-3p Represses Hepatic Stellate Cells Activation by Negatively Regulating the JAG1/Notch3 Signaling Pathway. Digestive diseases and sciences 15 32144602
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
2019 Downregulation of AKT and MDM2, Melatonin Induces Apoptosis in AGS and MGC803 Cells. Anatomical record (Hoboken, N.J. : 2007) 14 30809951
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
2021 A novel mechanism of the lncRNA PTTG3P/miR-142-5p/JAG1 axis modulating tongue cancer cell phenotypes through the Notch1 signaling. Cells & development 13 34952204
2020 JAG1, Regulated by microRNA-424-3p, Involved in Tumorigenesis and Epithelial-Mesenchymal Transition of High Proliferative Potential-Pituitary Adenomas. Frontiers in oncology 13 33425722
2019 Alagille Syndrome: A Novel Mutation in JAG1 Gene. Frontiers in pediatrics 13 31157196
2019 miR-34a-5p Inhibits Cell Proliferation, Migration and Invasion Through Targeting JAG1/Notch1 Pathway in HPV-Infected Human Epidermal Keratinocytes. Pathology oncology research : POR 13 31781973
2022 Melatonin Induces AGS Gastric Cancer Cell Apoptosis via Regulating PERK/eIF2α and HSF1/NF-κB Signaling Pathway. Annals of clinical and laboratory science 12 35181617
2021 Senescent cell removal via JAG1-NOTCH1 signalling in the epidermis. Experimental dermatology 12 33891780
2014 Spatial localization of the JAG1/Notch1/osteopontin cascade modulates extrahepatic metastasis in hepatocellular carcinoma. International journal of oncology 12 25176314
2022 Endothelial PERK-ATF4-JAG1 axis activated by T-ALL remodels bone marrow vascular niche. Theranostics 11 35401837
2022 Volatilomic Signatures of AGS and SNU-1 Gastric Cancer Cell Lines. Molecules (Basel, Switzerland) 11 35807254
2021 Anti-Cancer Potential of Afzelin towards AGS Gastric Cancer Cells. Pharmaceuticals (Basel, Switzerland) 11 34681197

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