Affinage

MAGED1

Melanoma-associated antigen D1 · UniProt Q9Y5V3

Length
778 aa
Mass
86.2 kDa
Annotated
2026-06-10
64 papers in source corpus 36 papers cited in narrative 36 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

MAGED1 (NRAGE/Dlxin-1) is a multifunctional scaffold/adaptor protein that integrates neurotrophin, BMP, transcription-factor and ubiquitin signaling to control developmental apoptosis, differentiation and neural function (PMID:10985348, PMID:16107717, PMID:18772898). In the neurotrophin axis it binds the p75NTR intracellular domain in a manner mutually exclusive with TrkA and drives NGF-dependent apoptosis through a JNK–mitochondrial–caspase cascade, a function genetically required in vivo where NRAGE-null mice phenocopy p75NTR knockouts in sympathetic neuron and hair-follicle apoptosis (PMID:10985348, PMID:12376548, PMID:18772898). The same membrane-proximal signaling also generates a p75NTR ICD that, with the NRAGE partner NEDD9, activates Rac1, while NRAGE conversely restrains TrkA-ERK signaling and neurite outgrowth (PMID:25472715, PMID:20127820). In non-canonical BMP signaling NRAGE is an obligatory component that engages the TAK1–TAB1–XIAP complex via its hexapeptide repeat domain to activate p38 MAPK and IKK/NF-κB (PMID:16107717, PMID:20100315, PMID:21789165). Through that hexapeptide repeat and a necdin-homology domain it binds Dlx/Msx homeodomain factors and necdin to form ternary complexes that relieve Msx repression and promote myogenic and osteogenic differentiation (PMID:11084035, PMID:15272023, PMID:28528976). NRAGE further acts as an adaptor coupling substrates to the ubiquitin system: it is itself degraded by the RING E3 ligase Praja1 and receives K63 ubiquitination from FBXO7, and it controls the stability or modification of SERT, PCNA, Che-1/AATF, PPARγ, RNF8/BARD1 and H2A (PMID:11959851, PMID:24947323, PMID:22457503, PMID:24710624, PMID:17488777, PMID:30121577, PMID:27035619, PMID:38123574). It binds RORα to sustain robustness of the circadian clock and partners with USP7 in paraventricular thalamus neurons to regulate H2A monoubiquitination and cocaine-adaptive behavior (PMID:20300063, PMID:38123574, PMID:30002119). A frameshift variant (Leu137PhefsTer4) that abolishes Praja1-dependent degradation and the protein's anti-migratory function links MAGED1 dysfunction to disease (PMID:42162770).

Mechanistic history

Synthesis pass · year-by-year structured walk · 25 steps
  1. 2000 High

    Established MAGED1's founding role as a death-promoting adaptor by showing it binds the p75NTR intracellular domain in competition with TrkA, linking a receptor to an apoptotic outcome.

    Evidence Yeast two-hybrid, in vitro binding and Co-IP with overexpression in sympathetic neuron precursors

    PMID:10985348

    Open questions at the time
    • Did not define the downstream death machinery
    • Did not resolve which domain mediates p75NTR binding
  2. 2000 High

    Defined a parallel transcriptional function by showing MAGED1 binds Dlx/Msx homeodomain factors through its hexapeptide repeat and modulates their activity.

    Evidence Yeast two-hybrid, Co-IP, reporter gene assays

    PMID:11084035

    Open questions at the time
    • Did not connect transcriptional and apoptotic roles
    • In vivo developmental relevance untested
  3. 2002 High

    Resolved the apoptotic cascade downstream of NRAGE as a JNK-dependent mitochondrial-caspase pathway, converting the binding observation into a defined mechanism.

    Evidence Inducible NRAGE adenovirus, JNK inhibition, dominant-negative c-Jun, cytochrome c fractionation, caspase assays

    PMID:12376548

    Open questions at the time
    • How NRAGE activates JNK was not identified
    • Did not test requirement in vivo
  4. 2002 High

    Identified the first regulator of NRAGE stability, showing Praja1 ubiquitinates and degrades it to down-regulate Dlx5-dependent transcription.

    Evidence GST pulldown, Co-IP, in vivo ubiquitination, RING mutant, proteasome rescue, reporter assay

    PMID:11959851

    Open questions at the time
    • Physiological context of degradation not defined
    • Other E3 ligases not excluded
  5. 2003 High

    Broadened NRAGE's death-receptor partners beyond p75NTR and defined a Ror2-dependent sequestration mechanism controlling its subcellular distribution and transcriptional output.

    Evidence Co-IP, domain mapping with chimeric UNC5H receptors, knockdown in PC12 cells, knockout fibroblast fractionation, reporter assays

    PMID:12598531 PMID:12754255

    Open questions at the time
    • Did not unify nuclear vs membrane localization control
    • Crosstalk between receptor partners untested
  6. 2004 High

    Showed MAGED1 nucleates a necdin–Msx ternary complex that relieves transcriptional repression and promotes myogenic differentiation, defining a domain-resolved adaptor logic.

    Evidence In vitro binding, endogenous complex detection, reporter and differentiation assays in C2C12 cells

    PMID:15272023

    Open questions at the time
    • In vivo myogenic requirement not shown here
    • Did not address other homeodomain partners
  7. 2005 High

    Established NRAGE as a mandatory, Smad-independent component of non-canonical BMP signaling by linking it to the TAK1-TAB1-XIAP module driving p38 activation.

    Evidence Co-IP, dominant-negative and siRNA loss-of-function, p38 phosphorylation and apoptosis assays in neural progenitors

    PMID:16107717

    Open questions at the time
    • Direct XIAP-binding domain not yet mapped
    • Receptor-level recruitment unresolved
  8. 2005 Medium

    Extended NRAGE's interactome to growth-suppression (BRCA2) and to a cytosolic prion-protein/mitochondrial axis, hinting at broader regulatory roles.

    Evidence Co-IP, RNAi epistasis, proliferation assays; yeast two-hybrid, in vitro binding and mitochondrial membrane potential assays

    PMID:15911347 PMID:15930293

    Open questions at the time
    • Single-lab observations
    • Mechanism linking these partners to apoptosis unclear
  9. 2007 Medium

    Showed NRAGE drives death partly by cytoplasmic sequestration and proteasomal degradation of the anti-apoptotic factor Che-1/AATF.

    Evidence Co-IP, EGFP localization, proteasome inhibitor and overexpression rescue

    PMID:17488777

    Open questions at the time
    • E3 ligase for Che-1 not identified
    • In vivo relevance untested
  10. 2008 High

    Provided genetic proof that NRAGE is required in vivo for developmental apoptosis, phenocopying and extending p75NTR knockout phenotypes.

    Evidence NRAGE knockout mice, apoptosis quantification, primary neuron culture, JNK assays, hair follicle analysis

    PMID:18772898

    Open questions at the time
    • Motoneuron-specific p75NTR-independent mechanism unresolved
    • Did not address non-apoptotic roles
  11. 2010 High

    Diversified MAGED1's physiology into circadian, neurotrophic-outgrowth, NF-κB and myogenic regulation, showing it tunes diverse transcriptional and signaling outputs.

    Evidence Maged1 knockout behavioral analysis with RORα binding/reporter assays; RNAi/overexpression of TrkA signaling; XIAP-TAK1-TAB1/IKK NF-κB assays; knockout myoblast differentiation with p21 readout

    PMID:20100315 PMID:20127820 PMID:20300063 PMID:20646279

    Open questions at the time
    • Tissue-specific contributions of each role not separated
    • Direct vs indirect transcriptional effects mixed
  12. 2011 Medium

    Mapped the unique hexapeptide repeat domain as the direct XIAP-binding and NF-κB-activating module, enabling a peptide inhibitor of the pathway.

    Evidence FRET, deletion mutagenesis, p38/caspase/NF-κB assays, peptide inhibitor in P19 cells

    PMID:21789165

    Open questions at the time
    • Structural basis of the interaction unresolved
    • Single-lab functional readouts
  13. 2012 Medium

    Defined MAGED1 as a substrate-targeting adaptor for ubiquitylation of SERT and as required for oxytocin maturation, linking it to monoaminergic and neuropeptide systems and behavior.

    Evidence Knockout mice with ubiquitylation/serotonin uptake assays; oxytocin RIA/ELISA and OT rescue with behavior

    PMID:22457503 PMID:22865874

    Open questions at the time
    • E3 ligase partnering MAGED1 on SERT not defined
    • Mechanism of oxytocin processing role unknown
  14. 2012 Medium

    Showed NRAGE restrains Ror2-Src-FAK signaling to inhibit cell migration, adding a cytoskeletal/motility arm to its functions.

    Evidence Co-IP of ternary complex, kinase activity and migration assays in B16 cells

    PMID:23142633

    Open questions at the time
    • In vivo metastasis relevance untested
    • Direct vs scaffold-mediated Src inhibition unclear
  15. 2013 Medium

    Connected Praja1-mediated NRAGE degradation to a cellular output, showing it controls NGF-induced neurite formation.

    Evidence Co-localization, proteasome rescue, stable overexpression and neurite assays in PC12 cells

    PMID:23717400

    Open questions at the time
    • Signal regulating Praja1 activity unknown
    • In vivo relevance untested
  16. 2014 Medium

    Expanded MAGED1's ubiquitin-adaptor and transcriptional repertoire, linking it to PCNA stabilization, CREB-dependent transcription/synaptic plasticity, and FBXO7-mediated K63 ubiquitination that builds the BMP signaling complex.

    Evidence Co-IP/ubiquitination/USP10 and rescue assays for PCNA; Co-IP/ChIP/reporter with KO LTP for CREB; yeast two-hybrid, K63-linked ubiquitination and NF-κB reporter for FBXO7

    PMID:24700102 PMID:24710624 PMID:24947323

    Open questions at the time
    • How a single scaffold coordinates so many ubiquitin events unresolved
    • Single-lab mechanistic studies
  17. 2015 Medium

    Defined the p75NTR ICD–NRAGE–NEDD9 axis as a Rac1-activating, cell-spreading module distinct from the apoptotic pathway.

    Evidence COS7 bioassay, cleavage inhibitors, yeast two-hybrid for NEDD9, Co-IP, Rac1 activation and dominant-negative constructs

    PMID:25472715

    Open questions at the time
    • In vivo relevance untested
    • Reciprocal NEDD9 validation limited
  18. 2016 Medium

    Added a DNA-repair function, showing NRAGE stabilizes RNF8/BARD1 and is required for efficient homologous recombination.

    Evidence Ternary complex Co-IP, ubiquitination and HRR reporter assays, knockdown sensitivity and xenograft

    PMID:27035619

    Open questions at the time
    • Nuclear localization control during DDR unclear
    • Single-lab study
  19. 2016 Medium

    Showed selective positive regulation of a subset of bHLH-PAS transcription factors via cytoplasmic interaction with nascent proteins, refining MAGED1's transcriptional-chaperone role.

    Evidence Co-IP, reporter assays, subcellular localization

    PMID:27472814

    Open questions at the time
    • Basis of partner selectivity unresolved
    • In vivo significance untested
  20. 2017 Medium

    Linked MAGED1 to osteoblast differentiation and to Wnt suppression via β-catenin O-GlcNAcylation, extending its developmental and signaling reach.

    Evidence Co-IP, Runx2 reporter and differentiation assays; Xenopus axis duplication, O-GlcNAc detection and Co-IP

    PMID:28427939 PMID:28528976

    Open questions at the time
    • Enzyme mediating β-catenin O-GlcNAcylation not identified
    • Single-lab studies
  21. 2018 High

    Established metabolic and addiction-related roles: MAGED1 destabilizes PPARγ to limit adiposity, inhibits NF-κB via IKKβ in odontogenesis, and is required in cortico-accumbal circuits for cocaine sensitization.

    Evidence Knockout mice with PPARγ stability/adipocyte assays; Co-IP/IKK-inhibitor differentiation assays; conditional cell-type-specific KO with electrophysiology and in vivo microdialysis

    PMID:29448842 PMID:30002119 PMID:30121577

    Open questions at the time
    • Molecular link between MAGED1 and dopamine release not resolved
    • Cell-type specificity of metabolic roles unclear
  22. 2020 Low

    Placed MAGED1 downstream of CDK4/6-E2F1 to promote FBP1 degradation and glycolysis in pancreatic cancer.

    Evidence CDK4/6 inhibitor, E2F1 reporter, FBP1 stability and glycolysis assays

    PMID:32987196

    Open questions at the time
    • No direct MAGED1-FBP1 interaction confirmed
    • Mechanism inferred from pharmacology and expression
  23. 2021 Medium

    Showed MAGED1 expression is itself controlled post-transcriptionally by m6A/YTHDF1-driven translation, with downstream PCNA-dependent proliferation in pulmonary hypertension.

    Evidence m6A-RIP-seq, RNA-IP, YTHDF1 and METTL3 knockout, genetic ablation, PCNA Western and proliferation assays

    PMID:33465322

    Open questions at the time
    • Whether this regulation operates in other tissues unknown
    • Single-lab study
  24. 2023 High

    Defined MAGED1 as a USP7-partnering scaffold controlling H2A monoubiquitination in thalamic neurons to drive cocaine-adaptive behavior, providing an epigenetic mechanism for its addiction phenotype.

    Evidence Vglut2-Cre conditional knockout, USP7 inhibition, H2A monoUb ChIP, transcriptome and locomotor sensitization assays

    PMID:38123574

    Open questions at the time
    • Genome-wide targets of the MAGED1-USP7 epigenetic activity not fully mapped
    • Reciprocal USP7 binding domain not defined
  25. 2026 Medium

    Connected MAGED1 dysfunction to disease, showing a frameshift variant disrupts Praja1 binding, stabilizes truncated protein, and abolishes anti-migratory function.

    Evidence Co-IP, immunofluorescence, Western blot, wound healing and cell cycle/apoptosis assays

    PMID:42162770

    Open questions at the time
    • Specific disease and patient-level consequences not detailed here
    • Single-lab variant follow-up

Open questions

Synthesis pass · forward-looking unresolved questions
  • How a single scaffold selectively coordinates its many ubiquitin-, transcription-, and signaling partners in a context-specific manner, and the structural basis of its domain interactions, remains unresolved.
  • No structural model of domain-partner interactions
  • Mechanism determining which substrate/pathway is engaged in a given cell type is unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 5 GO:0140096 catalytic activity, acting on a protein 4 GO:0060090 molecular adaptor activity 3 GO:0098772 molecular function regulator activity 3
Localization
GO:0005634 nucleus 3 GO:0005829 cytosol 2 GO:0005886 plasma membrane 2
Pathway
R-HSA-392499 Metabolism of proteins 5 R-HSA-5357801 Programmed Cell Death 4 R-HSA-74160 Gene expression (Transcription) 4 R-HSA-162582 Signal Transduction 3 R-HSA-73894 DNA Repair 1 R-HSA-9909396 Circadian clock 1
Partners
FBXO7NEDD9P75NTRPRAJA1RORATAK1USP7XIAP
Complex memberships
RNF8-BARD1-NRAGE complexTAK1-TAB1-XIAP complexnecdin-MAGED1-Msx ternary complex

Evidence

Reading pass · 36 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2000 NRAGE (MAGED1) directly binds the p75 neurotrophin receptor (p75NTR) intracellular domain in vitro and in vivo; this interaction is functionally exclusive with TrkA binding to p75NTR. NRAGE association with the plasma membrane occurs when NGF is bound to p75NTR, and NRAGE overexpression facilitates cell cycle arrest and NGF-dependent apoptosis in sympathetic neuron precursors. Yeast two-hybrid, in vitro binding, co-immunoprecipitation, overexpression in sympathetic neuron precursor cells Neuron High 10985348
2002 NRAGE-induced apoptosis proceeds through a JNK-dependent mitochondrial pathway: induced NRAGE expression activates JNK, causes cytosolic accumulation of cytochrome c, and activates caspases-3, -7, and -9; blocking JNK or dominant-negative c-Jun ablates NRAGE-mediated caspase activation and cell death. Inducible recombinant NRAGE adenovirus, pharmacological JNK inhibition, dominant-negative overexpression, cytochrome c fractionation, caspase activity assays The Journal of biological chemistry High 12376548
2000 MAGED1 (Dlxin-1) binds Dlx5, Dlx7, and Msx2 homeodomain proteins through its hexapeptide repeat domain, forms homomultimers in vivo, and activates Dlx5-dependent transcriptional function in reporter gene assays. Yeast two-hybrid, co-immunoprecipitation, transfection/reporter gene assay The Journal of biological chemistry High 11084035
2002 The RING finger E3 ubiquitin ligase Praja1 binds the C-terminal necdin homology domain of MAGED1 (Dlxin-1) and promotes its ubiquitination and proteasome-dependent degradation, thereby down-regulating Dlx5-dependent transcriptional activity. Yeast two-hybrid, GST pulldown, co-immunoprecipitation, proteasome inhibitor rescue, RING-finger mutant, in vivo ubiquitination assay, reporter gene assay The Journal of biological chemistry High 11959851
2003 UNC5H1 induces apoptosis through a direct interaction between its ZU-5 domain (plus adjacent PEST sequence) and NRAGE; chimeric UNC5H2/3 receptors engineered with this region gain NRAGE binding and increased apoptosis, and UNC5H1 fails to induce apoptosis in PC12 cells lacking endogenous NRAGE. Co-immunoprecipitation, domain mapping with chimeric receptors, NRAGE knockdown/overexpression in PC12 cells, apoptosis assays The Journal of biological chemistry High 12598531
2003 Ror2 (but not Ror1) associates with MAGED1 (Dlxin-1) via its cytoplasmic C-terminal proline/serine-threonine-rich region interacting with the necdin homology domain of Dlxin-1. This interaction sequesters Dlxin-1 in membranous compartments, preventing its nuclear localization, and thereby modulates Msx2 transcriptional activity. Co-immunoprecipitation, transient expression, immunohistochemistry, subcellular fractionation of Ror2−/− fibroblasts, reporter assay The Journal of biological chemistry High 12754255
2004 MAGED1 directly interacts with necdin via its MAGE homology domain and with Msx1/Msx2 via its hexapeptide repeat domain, forming a ternary complex that releases Msx-dependent transcriptional repression and promotes myogenic differentiation of C2C12 cells. In vitro binding assay, co-immunoprecipitation, endogenous complex detection in differentiating cells, transcriptional reporter assay, stable transfection + differentiation assay The Journal of biological chemistry High 15272023
2005 NRAGE is a mandatory component of the non-canonical BMP signaling cascade: NRAGE binds and functions with the TAK1-TAB1-XIAP complex to activate p38 MAPK and induce apoptosis in neural progenitors; disruption of NRAGE blocks p38 activation independently of Smad signaling. Co-immunoprecipitation, dominant-negative constructs, siRNA knockdown, p38 phosphorylation assays, apoptosis assays in neural progenitors Molecular and cellular biology High 16107717
2005 BRCA2 binds and stabilizes MAGED1 protein; expression of BRCA2 and MAGED1 synergistically suppresses cell proliferation independently of the p53 pathway, and MAGED1 expression is required for BRCA2-mediated growth suppression. Co-immunoprecipitation, RNAi knockdown of MAGED1, cell proliferation assays in multiple cell lines Cancer research Medium 15930293
2005 Cytosolic PrP(C) constructs interact directly with NRAGE (identified by yeast two-hybrid, confirmed by in vitro binding and co-immunoprecipitation); co-expression of NRAGE and cytosolic PrP affects mitochondrial membrane potential, and NRAGE accumulates in perinuclear aggresomes upon proteasome inhibition. Yeast two-hybrid, in vitro binding, co-immunoprecipitation, subcellular localization (co-localization in aggresomes), mitochondrial membrane potential assay Molecular and cellular neurosciences Medium 15911347
2007 NRAGE interacts with the anti-apoptotic factor Che-1/AATF and sequesters it in the cytoplasm, preventing nuclear localization; NRAGE overexpression promotes proteasome-dependent degradation of Che-1, and Che-1 overexpression completely reverts NRAGE-induced cell death. Co-immunoprecipitation, EGFP-NRAGE subcellular localization, proteasome inhibitor assay, overexpression rescue experiments Journal of cell science Medium 17488777
2008 NRAGE is required in vivo for developmental apoptosis: NRAGE knockout mice have defects in sympathetic neuron apoptosis similar to p75NTR knockouts, show attenuated BDNF-dependent JNK activation, exhibit identical hair follicle catagen defects as p75NTR knockouts, and display additional motoneuron apoptosis defects not seen in p75NTR knockouts. NRAGE knockout mouse generation, histological apoptosis quantification, primary sympathetic neuron culture, JNK activation assay, hair follicle analysis Cell death and differentiation High 18772898
2010 MAGED1 binds RORα and regulates circadian clock gene expression (Bmal1, Rev-erbα, E4bp4) through RORE elements; Maged1 knockout mice show shortened circadian period and altered rest-activity bouts, demonstrating MAGED1 is required for robustness of the molecular clock. Genetic screen, Maged1 knockout mice behavioral analysis, in vitro and in vivo binding assays, reporter gene assays with RORE elements The EMBO journal High 20300063
2010 NRAGE is a negative regulator of NGF-induced neurite outgrowth: NRAGE knockdown accelerates NGF-mediated neurite outgrowth and increases TrkA-ERK activation; NRAGE downregulates TrkA expression post-transcriptionally and blocks NGF-induced TrkA phosphorylation at tyrosine-490. RNAi knockdown, overexpression, MEK inhibitor treatment, TrkA phosphorylation assays, neurite outgrowth quantification in PC12 cells Journal of neuroscience research Medium 20127820
2010 NRAGE acts via the XIAP-TAK1-TAB1 complex to activate IKK-α/β phosphorylation and NF-κB transcriptional activation in the non-canonical BMP pathway; siRNA ablation of NRAGE inhibits NF-κB activation, and ablation of TAK1/TAB1 blocks NRAGE-induced NF-κB activation. siRNA knockdown, morpholino knockdown, IKK phosphorylation assay, NF-κB luciferase reporter assay, cytokine profiling BMC biology Medium 20100315
2011 NRAGE's unique hexapeptide repeat domain directly interacts with XIAP (demonstrated by FRET), and this domain is responsible for downstream NF-κB activation and IKK subunit phosphorylation in BMP signaling; a peptide modeled after this repeat domain inhibits NF-κB activation and apoptosis in P19 cells. FRET, deletion mutagenesis, p38 phosphorylation assay, caspase-3 cleavage assay, NF-κB reporter assay, peptide inhibitor PloS one Medium 21789165
2012 MAGED1 binds SERT (serotonin transporter) via its necdin homology domain and promotes SERT ubiquitylation; MAGED1 knockout mice show hypoactive serotonergic function with hyperexpression of SERT due to decreased ubiquitylation, and MAGED1 overexpression decreases SERT protein level and serotonin uptake activity. Co-immunoprecipitation, MAGED1 knockout mice, siRNA knockdown, ubiquitylation assays, serotonin uptake assays, Western blot The Journal of neuroscience High 22457503
2012 Loss of Maged1 severely reduces mature oxytocin levels in the hypothalamus without reducing precursor levels, indicating MAGED1 is required for OT processing or stability; oxytocin administration rescues social memory deficits in Maged1 knockout mice. Maged1 knockout mice, RIA/ELISA for oxytocin and precursors, OT rescue experiment, behavioral assays Human molecular genetics Medium 22865874
2012 NRAGE blocks the Ror2-Src interaction and inhibits Ror2-mediated cell migration by decreasing Src and focal adhesion kinase (FAK) activity; NRAGE sharply blocks the interaction between Src SH1 domain and the C-terminus of Ror2. Co-immunoprecipitation, kinase activity assays, overexpression/knockdown, migration assay in B16/B16-BL6 cells Cancer genetics Medium 23142633
2013 The ubiquitin ligase Praja1 co-localizes with NRAGE and reduces NRAGE levels via proteasome-dependent degradation; Praja1 overexpression suppresses NGF-induced neurite formation in PC12 cells through NRAGE degradation. Co-localization (immunofluorescence), Western blot, proteasome inhibitor rescue, stable overexpression in PC12 cells, neurite assay PloS one Medium 23717400
2014 MAGED1 co-interacts with CREB through its hexapeptide repeat domain; Maged1 knockout reduces CREB-dependent transcription and BDNF levels, and is associated with impaired long-term potentiation and spatial learning. Co-immunoprecipitation, chromatin immunoprecipitation, luciferase reporter assay, LTP electrophysiology, Maged1 knockout mice, Western blot Molecular neurobiology Medium 24700102
2014 NRAGE physically interacts with PCNA via DNA polymerase III subunit and stabilizes PCNA by reducing K48-linked polyubiquitination; knockdown of NRAGE promotes PCNA proteasomal degradation via USP10 regulation, and PCNA overexpression rescues growth inhibition in NRAGE-deficient esophageal cancer cells. Co-immunoprecipitation, ubiquitination assay, USP10 identification, cell growth/cycle assays, rescue by PCNA overexpression, in vivo xenograft Carcinogenesis Medium 24710624
2014 FBXO7 interacts with NRAGE and mediates Lys-63-linked (non-degradative) polyubiquitination of NRAGE; this promotes formation of the NRAGE-TAK1-TAB1 and BMP receptor-NRAGE-TAK1-TAB1 complexes and upregulates NF-κB activity. Yeast two-hybrid, co-immunoprecipitation, K63-linked ubiquitination assay, FBXO7 knockdown/overexpression, NF-κB reporter assay Cellular and molecular life sciences Medium 24947323
2015 p75NTR-dependent Rac1 activation requires proteolytic cleavage of p75NTR (by ADAM17 and γ-secretase) to generate the intracellular domain (ICD), and the ICD signals through NRAGE and a newly identified NRAGE-binding partner NEDD9 to activate Rac1 and promote cell spreading. Bioassay in COS7 cells, pharmacological cleavage inhibitors, yeast two-hybrid for NEDD9, co-immunoprecipitation, Rac1 activation assay, dominant-negative constructs Journal of cell science Medium 25472715
2016 NRAGE is required for efficient homologous recombination repair of double-strand breaks; NRAGE regulates stability of RNF8 and BARD1 via ubiquitin-proteolytic pathway and forms a ternary complex with RNF8 and BARD1 (via their RING domains), facilitating their interaction and DDR. Co-immunoprecipitation (ternary complex), ubiquitination assay, HRR reporter assay, knockdown with DNA damage sensitivity assays in vitro and in vivo xenograft Cell death and differentiation Medium 27035619
2016 MAGED1 binds and positively regulates a select subset of bHLH PAS transcription factors (SIM1, SIM2, NPAS4, ARNT2) but not others (AhR, HIF1α, ARNT); interaction is mediated by PAS repeat regions and MAGED1 appears to interact with nascent bHLH PAS proteins in the cytoplasm to enhance their function prior to nuclear import, without affecting their protein levels. Co-immunoprecipitation, transcriptional reporter assay, subcellular localization analysis The FEBS journal Medium 27472814
2017 Necdin promotes osteoblast differentiation through formation of a complex with MAGED1 and Dlx5, and activation of Runx2 promoter; co-expression of necdin and MAGED1 is required to achieve osteoblast-specific marker induction. Co-immunoprecipitation, stable transfection, osteoblast differentiation assay, Runx2 reporter assay Biochemical and biophysical research communications Medium 28528976
2017 NRAGE induces O-GlcNAcylation of β-catenin/Arm, which causes failure of the association between β-catenin and pygopus (required for Wnt target gene transcription), thereby suppressing Wnt pathway output despite promoting β-catenin nuclear localization. Reporter assay, RNAi, Xenopus axis duplication assay, O-GlcNAc modification detection, co-immunoprecipitation Biochemical and biophysical research communications Medium 28427939
2018 MAGED1 binds PPARγ and suppresses its stability and transcriptional activity; MAGED1-deficient mice show increased PPARγ protein levels, more adipocyte precursors, and hyperplasia of white adipose tissue, with improved insulin sensitivity. Co-immunoprecipitation, MAGED1 knockout mice, PPARγ stability assay, target gene expression, adipocyte differentiation assay The Journal of endocrinology Medium 30121577
2018 Maged1 is critical for cortico-accumbal neurotransmission and cocaine-induced dopamine release in the nucleus accumbens; expression of Maged1 in the prefrontal cortex and amygdala (but not in dopaminergic or striatal GABAergic neurons) is required for cocaine-mediated behavioral sensitization. Maged1 knockout mice, conditional knockout (cell-type specific), electrophysiology in brain slices, in vivo microdialysis, conditioned place preference, drug self-administration EMBO reports High 30002119
2010 Maged1 deficiency results in reduced p21CIP1/WAF1 levels, defective cell cycle exit, and impaired myotube maturation during myoblast differentiation; in vivo this causes delayed muscle regeneration after injury. Maged1 knockout mice, in vitro myoblast differentiation, p21 Western blot, cell cycle analysis, in vivo muscle injury model BMC cell biology Medium 20646279
2018 NRAGE binds IKKβ (co-immunoprecipitation) and inhibits the NF-κB signaling pathway; NRAGE knockdown promotes odontogenic differentiation through increased NF-κB1 nuclear translocation and p65 phosphorylation, effects reversed by an IKK inhibitor. Co-immunoprecipitation, confocal microscopy, lentivirus-mediated shRNA knockdown, IKK inhibitor, differentiation assays Connective tissue research Medium 29448842
2020 The CDK4/6-E2F1 signaling axis increases MAGED1 expression, which in turn promotes FBP1 degradation and aerobic glycolysis (Warburg effect) in pancreatic cancer; CDK4/6 inhibitor PD0332991 stabilizes FBP1 by repressing MAGED1 expression. CDK4/6 inhibitor treatment, E2F1 reporter assay, FBP1 stability assay, glycolysis measurements The international journal of biochemistry & cell biology Low 32987196
2021 YTHDF1 recognizes m6A-modified MAGED1 mRNA and promotes its translation in an m6A-dependent manner (absent in METTL3-deficient cells); increased MAGED1 protein promotes PASMC proliferation through PCNA upregulation and contributes to pulmonary hypertension. m6A-RIP sequencing, RNA immunoprecipitation, YTHDF1 knockout mice, MAGED1 genetic ablation, METTL3 knockout, PCNA Western blot, proliferation assays American journal of respiratory and critical care medicine Medium 33465322
2023 Maged1 acts as a scaffold that partners with USP7 to regulate H2A monoubiquitination in paraventricular thalamus (PVT) neurons; chronic cocaine use increases H2A monoubiquitination in PVT, and Maged1-specific inactivation in thalamic Vglut2 neurons or USP7 inhibition blocks cocaine-evoked H2A monoubiquitination and cocaine locomotor sensitization. Conditional Maged1 knockout (Vglut2-Cre), USP7 pharmacological inhibition, H2A monoubiquitination ChIP, locomotor sensitization behavioral assay, transcriptome analysis Nature communications High 38123574
2026 A frameshift variant in MAGED1 (Leu137PhefsTer4) disrupts the interaction between MAGED1 and the E3 ubiquitin ligase Praja-1 (co-immunoprecipitation), impairs degradation of the truncated protein leading to its abnormal stabilization, and abolishes MAGED1's inhibitory effect on cell migration. Co-immunoprecipitation, immunofluorescence, Western blot, wound healing assay, cell cycle/apoptosis assay Neurobiology of disease Medium 42162770

Source papers

Stage 0 corpus · 64 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2000 NRAGE, a novel MAGE protein, interacts with the p75 neurotrophin receptor and facilitates nerve growth factor-dependent apoptosis. Neuron 243 10985348
2002 NRAGE, a p75 neurotrophin receptor-interacting protein, induces caspase activation and cell death through a JNK-dependent mitochondrial pathway. The Journal of biological chemistry 116 12376548
2021 YTHDF1 Regulates Pulmonary Hypertension through Translational Control of MAGED1. American journal of respiratory and critical care medicine 111 33465322
2003 UNC5H1 induces apoptosis via its juxtamembrane region through an interaction with NRAGE. The Journal of biological chemistry 97 12598531
2002 A RING finger protein Praja1 regulates Dlx5-dependent transcription through its ubiquitin ligase activity for the Dlx/Msx-interacting MAGE/Necdin family protein, Dlxin-1. The Journal of biological chemistry 93 11959851
2000 Dlxin-1, a novel protein that binds Dlx5 and regulates its transcriptional function. The Journal of biological chemistry 92 11084035
2012 MAGE-D1 regulates expression of depression-like behavior through serotonin transporter ubiquitylation. The Journal of neuroscience : the official journal of the Society for Neuroscience 75 22457503
2004 Necdin interacts with the Msx2 homeodomain protein via MAGE-D1 to promote myogenic differentiation of C2C12 cells. The Journal of biological chemistry 67 15272023
2005 NRAGE mediates p38 activation and neural progenitor apoptosis via the bone morphogenetic protein signaling cascade. Molecular and cellular biology 63 16107717
2008 NRAGE, a p75NTR adaptor protein, is required for developmental apoptosis in vivo. Cell death and differentiation 59 18772898
2003 The receptor tyrosine kinase Ror2 associates with the melanoma-associated antigen (MAGE) family protein Dlxin-1 and regulates its intracellular distribution. The Journal of biological chemistry 58 12754255
2012 Loss of Maged1 results in obesity, deficits of social interactions, impaired sexual behavior and severe alteration of mature oxytocin production in the hypothalamus. Human molecular genetics 56 22865874
2007 NRAGE associates with the anti-apoptotic factor Che-1 and regulates its degradation to induce cell death. Journal of cell science 53 17488777
2009 MAGE-D1 inhibits proliferation, migration and invasion of human breast cancer cells. Oncology reports 49 19639218
2005 BRCA2 suppresses cell proliferation via stabilizing MAGE-D1. Cancer research 47 15930293
2014 NRAGE promotes cell proliferation by stabilizing PCNA in a ubiquitin-proteasome pathway in esophageal carcinomas. Carcinogenesis 44 24710624
2010 Interaction of MAGED1 with nuclear receptors affects circadian clock function. The EMBO journal 36 20300063
2005 Interaction of PrP with NRAGE, a protein involved in neuronal apoptosis. Molecular and cellular neurosciences 32 15911347
2006 NRAGE suppresses metastasis of melanoma and pancreatic cancer in vitro and in vivo. Cancer letters 30 17140727
2014 The F-box protein FBXO7 positively regulates bone morphogenetic protein-mediated signaling through Lys-63-specific ubiquitination of neurotrophin receptor-interacting MAGE (NRAGE). Cellular and molecular life sciences : CMLS 26 24947323
2012 Ror2-Src signaling in metastasis of mouse melanoma cells is inhibited by NRAGE. Cancer genetics 26 23142633
2005 Human NRAGE disrupts E-cadherin/beta-catenin regulated homotypic cell-cell adhesion. Biochemical and biophysical research communications 26 16125672
2010 A role for NRAGE in NF-kappaB activation through the non-canonical BMP pathway. BMC biology 25 20100315
2016 NRAGE promotes the malignant phenotype of hepatocellular carcinoma. Oncology letters 24 26998088
2018 Inhibition of PPARγ, adipogenesis and insulin sensitivity by MAGED1. The Journal of endocrinology 20 30121577
2016 NRAGE is involved in homologous recombination repair to resist the DNA-damaging chemotherapy and composes a ternary complex with RNF8-BARD1 to promote cell survival in squamous esophageal tumorigenesis. Cell death and differentiation 20 27035619
2014 Maged1 co-interacting with CREB through a hexapeptide repeat domain regulates learning and memory in mice. Molecular neurobiology 19 24700102
2010 Dlxin-1, a member of MAGE family, inhibits cell proliferation, invasion and tumorigenicity of glioma stem cells. Cancer gene therapy 17 21109781
2015 MAGED1 is a negative regulator of bone remodeling in mice. The American journal of pathology 16 26272363
2011 A small peptide modeled after the NRAGE repeat domain inhibits XIAP-TAB1-TAK1 signaling for NF-κB activation and apoptosis in P19 cells. PloS one 16 21789165
2010 NRAGE is a negative regulator of nerve growth factor-stimulated neurite outgrowth in PC12 cells mediated through TrkA-ERK signaling. Journal of neuroscience research 16 20127820
2010 Maged1, a new regulator of skeletal myogenic differentiation and muscle regeneration. BMC cell biology 16 20646279
2016 Complex roles of NRAGE on tumor. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 15 27209410
2013 The ubiquitin ligase Praja1 reduces NRAGE expression and inhibits neuronal differentiation of PC12 cells. PloS one 15 23717400
2020 The CDK4/6 inhibitor PD0332991 stabilizes FBP1 by repressing MAGED1 expression in pancreatic ductal adenocarcinoma. The international journal of biochemistry & cell biology 13 32987196
2017 Necdin modulates osteogenic cell differentiation by regulating Dlx5 and MAGE-D1. Biochemical and biophysical research communications 13 28528976
2015 p75NTR-dependent Rac1 activation requires receptor cleavage and activation of an NRAGE and NEDD9 signaling cascade. Journal of cell science 13 25472715
2013 The roles of MAGE-D1 in the neuronal functions and pathology of the central nervous system. Reviews in the neurosciences 13 23314527
2006 Inhibition of adenovirus-mediated human MAGE-D1 on angiogenesis in vitro and in vivo. Molecular and cellular biochemistry 13 17149546
2018 The role of NRAGE subcellular location and epithelial-mesenchymal transition on radiation resistance of esophageal carcinoma cell. Journal of cancer research and therapeutics 12 29516958
2018 Deletion of Maged1 in mice abolishes locomotor and reinforcing effects of cocaine. EMBO reports 12 30002119
2016 Identification of novel NRAGE involved in the radioresistance of esophageal cancer cells. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 12 26738870
2011 MAGED1: molecular insights and clinical implications. Annals of medicine 12 21612333
2023 USP7/Maged1-mediated H2A monoubiquitination in the paraventricular thalamus: an epigenetic mechanism involved in cocaine use disorder. Nature communications 11 38123574
2017 Xp11.22 deletions encompassing CENPVL1, CENPVL2, MAGED1 and GSPT2 as a cause of syndromic X-linked intellectual disability. PloS one 10 28414775
2016 MAGED1 is a novel regulator of a select subset of bHLH PAS transcription factors. The FEBS journal 10 27472814
2010 Dlxin-1, a MAGE family protein, induces accelerated neurite outgrowth and cell survival by enhanced and early activation of MEK and Akt signalling pathways in PC12 cells. Experimental cell research 10 20595047
2010 Relationship between NRAGE and the radioresistance of esophageal carcinoma cell line TE13R120. Chinese journal of cancer 10 20868560
2009 NRAGE: a potential rheostat during branching morphogenesis. Mechanisms of development 10 19268530
2010 Mapping of NRAGE domains reveals clues to cell viability in BMP signaling. Apoptosis : an international journal on programmed cell death 7 19937275
2022 NRAGE Confers Radiation Resistance in 2D and 3D Cell Culture and Poor Outcome in Patients With Esophageal Squamous Cell Carcinoma. Frontiers in oncology 6 35433476
2018 Knockdown of NRAGE induces odontogenic differentiation by activating NF-κB signaling in mouse odontoblast-like cells. Connective tissue research 6 29448842
2017 Silencing of NRAGE induces autophagy via AMPK/Ulk1/Atg13 signaling pathway in NSCLC cells. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 6 28639909
2015 The Effect of NRAGE on cell cycle and apoptosis of human dental pulp cells and MDPC-23. International journal of clinical and experimental medicine 6 26379857
2020 Knockdown of NRAGE Impairs Homologous Recombination Repair and Sensitizes Hepatoblastoma Cells to Ionizing Radiation. Cancer biotherapy & radiopharmaceuticals 4 31916845
2017 NRAGE induces β-catenin/Arm O-GlcNAcylation and negatively regulates Wnt signaling. Biochemical and biophysical research communications 4 28427939
2022 Dynamic expression of Mage-D1 in rat dental germs and potential role in mineralization of ectomesenchymal stem cells. Scientific reports 3 36585447
2018 NRAGE is a potential diagnostic biomarker of hepatocellular carcinoma. Medicine 3 30508943
2023 The deficiency of Maged1 attenuates Parkinson's disease progression in mice. Molecular brain 2 36774489
2022 Knockdown of Maged1 inhibits cell cycle progression and causes cell death in mouse embryonic stem cells. Differentiation; research in biological diversity 2 35349880
2024 Study of role of melanoma-associated antigen D1 (MAGE-D1) in hepatocellular carcinoma. Journal of investigative medicine : the official publication of the American Federation for Clinical Research 1 39370811
2026 De novo variants in MAGED1 suggest a role in intellectual disability pathogenesis. Neurobiology of disease 0 42162770
2025 miR-2400 promotes proliferation of bovine skeletal muscle-derived satellite cells by regulating MAGED1 genes expression. Journal of muscle research and cell motility 0 40338441
2021 [Mage-D1 binding to activated p75NTR positively regulates mineralization of rat ectomesenchymal stem cells in vitro]. Nan fang yi ke da xue xue bao = Journal of Southern Medical University 0 34755671

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