Affinage

MEOX2

Homeobox protein MOX-2 · UniProt P50222

Length
304 aa
Mass
33.6 kDa
Annotated
2026-04-28
95 papers in source corpus 36 papers cited in narrative 36 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

MEOX2 (also known as GAX) is a homeodomain transcription factor that functions as a context-dependent regulator of cell proliferation, vascular homeostasis, and tissue-specific differentiation during development and in adult tissues. MEOX2 directly binds ATTA-containing promoter elements to transcriptionally activate the cyclin-dependent kinase inhibitors p21CIP1/WAF1 (via distal upstream sites) and p16INK4a, inducing cell cycle arrest and senescence in vascular smooth muscle cells and endothelial cells through mechanistically distinct DNA binding-dependent (p16) and DNA binding-independent (p21) modes (PMID:9224717, PMID:22206000, PMID:17074759, PMID:19340300). In development, MEOX2 is essential for limb myogenesis—acting upstream of Pax3 and Myf5—palatal shelf maintenance, and nociceptor function through regulation of Nav1.7/Nav1.9 sodium channels, while in cardiac endothelium it heterodimerizes with Tcf15 to drive fatty acid transporter expression and cardiac metabolic support (PMID:10403250, PMID:16284941, PMID:35029322, PMID:25561514). MEOX2 is itself regulated post-transcriptionally by miR-130a targeting its 3′-UTR, transcriptionally by ZEB2 repression relieved via miR-221, and post-translationally by ERK-mediated Ser155 phosphorylation affecting its stability and subnuclear distribution; it physically interacts with NF-κB p65/IκBβ to modulate inflammatory signaling, with Smads to mediate TGF-β cytostatic responses, and with PARP1 to support DNA repair in glioblastoma stem cells (PMID:17957028, PMID:20516212, PMID:35468210, PMID:20421348, PMID:19383287, PMID:41620199).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 1992 Medium

    Identifying MEOX2 as a novel homeobox gene expressed in paraxial mesoderm and somites established it as a transcription factor with potential roles in mesodermal patterning, prior to any knowledge of its targets or function.

    Evidence In situ hybridization expression profiling in mouse embryos

    PMID:1363541

    Open questions at the time
    • No functional data; expression pattern alone
    • No downstream targets identified
    • No loss-of-function data
  2. 1995 Medium

    Demonstrating that MEOX2/GAX is highly expressed in quiescent VSMCs and rapidly downregulated upon vascular injury linked it to growth-arrest maintenance, while promoter analysis identified Sp1, MEF2, and HRF-1 as upstream regulators of MEOX2 transcription.

    Evidence Northern blot of injured rat carotid arteries; deletion/mutagenesis analysis of the Gax promoter with transient transfection and protein-DNA binding assays

    PMID:7623821 PMID:7890661

    Open questions at the time
    • No direct demonstration that MEOX2 loss causes VSMC proliferation
    • Mechanism of growth arrest unknown
  3. 1997 High

    Establishing that MEOX2 inhibits proliferation via p21-dependent CDK2 inactivation and induces G0/G1 arrest—confirmed by resistance of p21-null cells—provided the first mechanistic link between MEOX2 and cell cycle control, while parallel work showed it also inhibits cardiomyocyte proliferation in vivo.

    Evidence Adenoviral overexpression, microinjection, p21-knockout fibroblasts, cdk2 activity assays; forced expression in chick hearts with PCNA staining

    PMID:9224717 PMID:9334288

    Open questions at the time
    • Whether MEOX2 directly binds p21 promoter unknown
    • Mechanism in cardiomyocytes could differ from VSMCs
  4. 1998 High

    Showing that MEOX2 induces apoptosis in mitogen-activated cells through Bax upregulation and Bcl-2 downregulation—independent of p21 and p53—revealed a second, distinct anti-proliferative output beyond cell cycle arrest.

    Evidence Adenoviral overexpression in Bax-knockout MEFs with Bcl-2/Bax Western blots and viability assays

    PMID:9649428

    Open questions at the time
    • Whether MEOX2 directly regulates Bax transcription or acts indirectly unknown
    • Apoptotic pathway not confirmed in vascular cells in vivo
  5. 1999 High

    Genetic ablation of Meox2 in mice revealed its essential role in limb myogenesis—acting upstream of Pax3 and Myf5—establishing MEOX2 as a master regulator of appendicular muscle development, while complementary work showed MEOX2 inhibits VSMC migration through p21-dependent integrin downregulation.

    Evidence Meox2-null mouse analysis with epistasis; adenoviral Gax transduction with migration assays, flow cytometry, and p21-KO fibroblasts

    PMID:10403250 PMID:10562309

    Open questions at the time
    • Direct transcriptional regulation of Pax3 by MEOX2 not demonstrated
    • Whether integrin regulation is transcriptionally direct unknown
  6. 2001 Medium

    Identifying physical interaction between the MEOX2 homeodomain and Pax3 provided a molecular basis for the genetic epistasis observed in limb myogenesis.

    Evidence Yeast two-hybrid and in vitro pulldown assays with domain mapping

    PMID:11423130

    Open questions at the time
    • Functional consequence of MEOX2-Pax3 interaction on target gene regulation not tested
    • No in vivo confirmation of the complex
  7. 2005 High

    Two key advances expanded MEOX2's role: (1) demonstration that MEOX2 loss in Alzheimer's brain endothelium reduces LRP1 and cerebrovascular function, and (2) identification of RNF10 as a physical interactor that enhances MEOX2-dependent p21 promoter activation.

    Evidence Gene transfer/silencing in human brain ECs and Meox2-KO mouse cerebrovascular analysis; yeast two-hybrid confirmed by co-IP with p21 reporter assay

    PMID:16116430 PMID:16335786

    Open questions at the time
    • Whether MEOX2 directly regulates LRP1 transcription not resolved
    • RNF10-MEOX2 interaction not tested for ubiquitination function
  8. 2006 High

    ChIP demonstrated that MEOX2 directly binds multiple ATTA-containing sites ~15 kb upstream of p21, requiring both the homeodomain and N-terminal domain, while knockout analysis revealed an unexpected role in palatal shelf maintenance after fusion.

    Evidence ChIP, domain deletion mutagenesis, reporter assays in endothelial cells; Meox2-null mouse histological analysis of palate

    PMID:16284941 PMID:17074759

    Open questions at the time
    • Whether the same distal elements are used in all cell types unknown
    • Palatal phenotype mechanism not molecularly defined
  9. 2007 High

    miR-130a was identified as a direct negative regulator of MEOX2 via its 3′-UTR, establishing the first post-transcriptional control mechanism and explaining serum-induced MEOX2 downregulation during angiogenesis; simultaneously, MEOX2 was placed as a TGF-β/Smad transcriptional target that cooperates with Smads to activate p21.

    Evidence 3′-UTR reporter assays with miR-130a target site deletion; RNAi, co-IP for Smad-MEOX2 complex, and p21 promoter dissection

    PMID:17957028 PMID:19383287

    Open questions at the time
    • Whether Smad-MEOX2 complex binds DNA cooperatively at specific sites not shown by ChIP
    • Other miRNAs targeting MEOX2 3′-UTR not systematically explored at this point
  10. 2010 High

    Two studies clarified MEOX2's interactions with inflammation and upstream transcriptional control: MEOX2 physically associates with NF-κB p65 and IκBβ in the nucleus to modulate NF-κB activity, and ZEB2 directly represses MEOX2 transcription through defined promoter sites, with miR-221 relieving this repression.

    Evidence Co-IP, immunofluorescence, domain deletion, NF-κB reporter assays; ChIP for ZEB2 binding, mutant miR-221 controls

    PMID:20421348 PMID:20516212

    Open questions at the time
    • In vivo relevance of NF-κB modulation by MEOX2 not tested
    • Whether ZEB2 repression operates in non-endothelial contexts unknown
  11. 2011 High

    Demonstrating that MEOX2 activates p16INK4a in a DNA binding-dependent manner but p21 in a DNA binding-independent manner resolved how a single transcription factor uses mechanistically distinct modes to engage two CDK inhibitor targets; suppression of MEOX2 by miR-130/301 family was shown to facilitate iPSC reprogramming.

    Evidence DNA-binding mutant overexpression with promoter reporters and senescence assays; miRNA-resistant MEOX2 construct and siRNA epistasis in iPSC assays

    PMID:21941297 PMID:22206000

    Open questions at the time
    • Cofactors mediating DNA binding-independent p21 activation unidentified
    • Mechanism by which MEOX2 blocks reprogramming beyond proliferation arrest not defined
  12. 2015 High

    Identification of Meox2/Tcf15 heterodimers as transcriptional determinants of heart capillary endothelial identity—driving CD36 and lipoprotein lipase for fatty acid uptake—revealed a metabolic function distinct from MEOX2's anti-proliferative roles.

    Evidence Microarray of freshly isolated ECs, genetic gain/loss-of-function, combined haplodeficiency mouse with cardiac contractility measurements

    PMID:25561514

    Open questions at the time
    • Direct DNA-binding sites for Meox2/Tcf15 heterodimer not mapped
    • Whether this metabolic program operates in non-cardiac endothelium unknown
  13. 2022 High

    Multiple studies revealed MEOX2 as an oncogenic transcription factor in glioblastoma—enhancing ERK signaling via Ser155 phosphorylation, directly activating Cathepsin S transcription, and regulating glycolytic/hypoxic gene programs—while also establishing its role in nociceptor function through control of Nav1.7/Nav1.9 expression.

    Evidence S155A mutagenesis and cerebral organoid models; ChIP-qPCR for CTSS; shRNA with RNA-seq in GSCs; Meox2-heterozygous mice with electrophysiology and transcriptomics

    PMID:35029322 PMID:35436995 PMID:35468210 PMID:35565433

    Open questions at the time
    • Whether Ser155 phosphorylation is the sole post-translational modification governing MEOX2 stability
    • Direct vs indirect regulation of sodium channel genes not resolved
    • Context-dependent switch between tumor-suppressive and oncogenic roles not mechanistically explained
  14. 2025 High

    MEOX2 mRNA was shown to be stabilized by NAT10-mediated ac4C modification, adding an epitranscriptomic layer of regulation, while identification of PARP1 as a MEOX2 interactor linked MEOX2 to DNA repair and PARP inhibitor sensitivity in glioblastoma.

    Evidence MeRIP-qPCR and RIP for ac4C modification in HUVECs; co-IP with mass spectrometry, PARylation assays, and PARP inhibitor sensitivity in GLICO organoid models

    PMID:41082000 PMID:41620199

    Open questions at the time
    • Whether ac4C modification is regulated in vivo during angiogenesis not tested
    • Structural basis of MEOX2-PARP1 interaction unknown
    • Whether MEOX2 stimulates PARP1 catalytic activity or serves as scaffold not distinguished

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the structural basis for MEOX2's DNA binding-independent activation of p21, the molecular determinants that switch MEOX2 between tumor-suppressive and oncogenic roles across tissue contexts, and whether MEOX2's metabolic functions in cardiac endothelium extend to other vascular beds.
  • No structural model of MEOX2 or its complexes available
  • Context-dependent transcriptional programs not systematically compared across tissues
  • In vivo relevance of many protein-protein interactions (Smads, PARP1, ABI2) not confirmed by genetic epistasis

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 9 GO:0003677 DNA binding 5
Localization
GO:0005634 nucleus 3
Pathway
R-HSA-74160 Gene expression (Transcription) 6 R-HSA-1640170 Cell Cycle 5 R-HSA-1266738 Developmental Biology 4 R-HSA-162582 Signal Transduction 4 R-HSA-5357801 Programmed Cell Death 2 R-HSA-73894 DNA Repair 1
Partners
ABI2NFKBIBPARP1PAX3RELARNF10TCF15
Complex memberships
MEOX2/NF-κB p65/IκBβ complexMEOX2/Smad complexMeox2/Tcf15 heterodimer

Evidence

Reading pass · 36 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1992 Mox-2 (MEOX2) is a homeobox transcription factor expressed in paraxial mesoderm and its derivatives (somites, sclerotome), defining a novel homeobox gene family involved in mesodermal regionalization and somitic differentiation in mouse embryos. In situ hybridization, expression profiling in mouse embryos Development Medium 1363541
1995 The Gax (MEOX2) homeobox gene is expressed in quiescent vascular smooth muscle cells (VSMCs) and is rapidly down-regulated in vivo following balloon angioplasty injury, mirroring the upregulation of early response genes such as c-myc and c-fos, suggesting a role in maintaining the non-proliferative VSMC phenotype. Northern blot analysis of rat carotid artery tissue after balloon injury Journal of Biological Chemistry Medium 7890661
1995 The Gax (MEOX2) promoter is regulated by at least three positive transcription factors: Sp1 (binding a G/C-rich element), MEF2/RSRF (MADS box factor binding the MEF2 site, with greatest transcriptional impact in cells with highest MEF2 activity), and a third factor (HRF-1) binding an inverted palindromic motif within the 138-bp minimal promoter. Deletion analysis, transient transfection, mutagenesis, protein-DNA binding assays, MEF2A overexpression Molecular and Cellular Biology High 7623821
1996 Protein localization of Mox-1 and Mox-2 during mouse development revealed distinct temporal onset: Mox-1 protein appears in newly formed mesoderm at 7.5 dpc, whereas Mox-2 protein is first detected at 9.0 dpc in already-formed somites, indicating distinct developmental roles despite overlapping mRNA expression patterns. Immunostaining/immunohistochemistry on mouse embryos at multiple timepoints International Journal of Developmental Biology Medium 9032023
1997 Gax (MEOX2) overexpression inhibits VSMC and fibroblast proliferation through a p53-independent, p21-dependent mechanism: Gax induces p21 expression, promotes p21 association with cdk2 complexes, decreases cdk2 activity, and causes G0/G1 arrest. Fibroblasts deficient in p21 are not susceptible to Gax-mediated growth inhibition. Recombinant protein microinjection, adenoviral overexpression, p21-knockout fibroblasts, cdk2 activity assay, cell cycle analysis Genes & Development High 9224717
1997 Gax (MEOX2) protein is expressed in the nuclei of cardiomyocytes late in chicken heart development when myocyte proliferation is declining; forced precocious nuclear Gax expression inhibits cardiomyocyte proliferation and perturbs heart morphogenesis (small ventricles, thinned compact zone), demonstrating a role as a negative regulator of cardiomyocyte proliferation. Adenoviral overexpression in chick hearts, immunohistochemistry, PCNA staining, clonal analysis Development Medium 9334288
1997 Angiotensin II suppresses Gax (MEOX2) mRNA expression in VSMCs via AT1 receptor signaling, while C-type natriuretic peptide (CNP) augments Gax expression through a cGMP cascade, identifying Gax as a downstream transcriptional effector of opposing vascular growth signaling pathways. RT-PCR/Northern blot in quiescent rat aortic VSMCs with pharmacological inhibitors and agonists Hypertension Medium 9039131
1998 Gax (MEOX2)-induced apoptosis requires mitogen activation and depends on Bax: forced Gax expression leads to Bcl-2 down-regulation and Bax up-regulation in mitogen-activated but not quiescent cultures, and Bax-null mouse embryonic fibroblasts are refractory to Gax-induced apoptosis. This cell death is independent of p21 and p53. Adenoviral overexpression, Bax-knockout MEFs, Western blot for Bcl-2/Bax, cell viability assays EMBO Journal High 9649428
1999 Mox2 (MEOX2) is essential for limb muscle development: Mox2 null mice show reduced limb muscle mass and loss of specific muscles, with downregulation of Pax3 and Myf5 but not MyoD in limb buds, placing MEOX2 upstream of Pax3/Myf5 in the genetic hierarchy of appendicular myogenesis. Mox2 null mouse genetic analysis, gene expression profiling, epistasis Nature High 10403250
1999 Gax (MEOX2) inhibits VSMC migration toward PDGF-BB, bFGF, and HGF through a p21-dependent mechanism, and specifically downregulates αvβ3 and αvβ5 integrin expression (β3 and β5 subunits) in VSMCs both in culture and after vascular injury in vivo. This effect is absent in p21-null fibroblasts but can be restored by exogenous p21 or p16. Adenoviral Gax transduction, migration assays, flow cytometry for integrin expression, p21/p53 knockout fibroblasts, in vivo vascular injury model Journal of Clinical Investigation High 10562309
2001 Mox1 and Mox2 (MEOX2) homeoproteins physically interact with Pax1 and Pax3 transcription factors; Mox2 shows preferential association with Pax3 over Pax1, and this interaction is mediated through the homeodomain of Mox. Yeast two-hybrid assay, in vitro biochemical pulldown assays FEBS Letters Medium 11423130
2005 MEOX2 expression is reduced in brain endothelial cells (BECs) in Alzheimer disease; restoring MEOX2/GAX expression in AD BECs stimulates angiogenesis, transcriptionally suppresses AFX1 forkhead transcription factor-mediated apoptosis, and increases LRP1 levels at the blood-brain barrier. In mice, Meox2 deletion reduces brain capillary density, resting cerebral blood flow, angiogenic response to hypoxia, and Aβ efflux due to reduced LRP levels. Viral-mediated gene silencing and transfer in human BECs, Meox2 knockout mouse analysis, transcriptional profiling, LRP expression assays Nature Medicine High 16116430
2005 MEOX2 binds to RING finger protein 10 (RNF10); the minimal RNF10 binding region of MEOX2 is a central region between the HQ-rich domain and the homeodomain (amino acids 101–185), and RNF10 co-expression enhances MEOX2 activation of the p21WAF1 promoter. Yeast two-hybrid screen of human heart cDNA library, in vitro pulldown, co-immunoprecipitation in mammalian cells, promoter reporter assay Molecular and Cellular Biochemistry Medium 16335786
2006 Meox-2 marks early palatal mesenchymal cells and is required for maintaining adherence of palatal shelves after fusion; Meox-2 null and heterozygous mice show cleft palate resulting from post-fusion breakdown rather than failure of elevation/fusion, revealing a novel role in maintaining palatal shelf adhesion. Meox-2 knockout mouse analysis, in situ hybridization, histological analysis Developmental Dynamics High 16284941
2006 GAX (MEOX2) directly activates p21WAF1/CIP1 expression in vascular endothelial cells through multiple upstream ATTA-containing AT-rich sequences (~15 kb upstream of ATG); GAX binds these sites in a homeodomain-dependent manner, requires both the homeodomain and N-terminal domain for full transactivation, and the ability to transactivate p21 correlates with G0/G1 arrest induction. Chromatin immunoprecipitation (ChIP), domain deletion mutagenesis, luciferase reporter assays, cell cycle analysis Journal of Biological Chemistry High 17074759
2007 miR-130a directly targets two sites in the GAX (MEOX2) 3'-UTR to down-regulate GAX expression in vascular endothelial cells in response to serum and proangiogenic factors, thereby promoting the angiogenic phenotype. A 280-bp fragment from the GAX 3'-UTR is required and sufficient to mediate serum-induced down-regulation when placed in a reporter construct. 3'-UTR luciferase reporter assay, forced miR-130a expression, miR-130a target site deletion analysis Blood High 17957028
2007 Meox2 is a TGF-β/Smad pathway transcriptional target; Meox2 knockdown prevents TGF-β1-induced cytostatic response in epithelial cells, ectopic Meox2 suppresses proliferation by inducing p21 requiring a distal p53-binding site region, and Meox2 forms protein complexes with Smads to cooperatively regulate p21 gene expression. Meox2 also inhibits TGF-β-induced epithelial-mesenchymal transition. RNA interference knockdown, ectopic overexpression, co-immunoprecipitation for Smad-Meox2 complex, promoter reporter assay, cell cycle analysis Molecular Oncology High 19383287
2009 MEOX2 (GAX) directly activates INK4a (p16) transcription by binding to the INK4a promoter as demonstrated by chromatin immunoprecipitation; MEOX2 expression increases during replicative senescence, forced MEOX2 expression induces premature senescence, and MEOX2-induced senescence is dependent on INK4a activity. Genome-scale cDNA overexpression screen, ChIP, senescence assays, INK4a-dependent epistasis PLoS One High 19340300
2010 ZEB2 represses GAX/MEOX2 transcription by binding to two identified ZEB2 binding sites in the GAX promoter; miR-221 upregulates GAX by downregulating ZEB2, and a mutant miR-221 fails to downregulate ZEB2 or upregulate GAX. This establishes a miR-221→ZEB2→GAX regulatory axis in vascular endothelial cells. miR-221 overexpression and inhibitor, ZEB2 identification by expression profiling, chromatin immunoprecipitation for ZEB2 binding sites, mutant miR-221 controls, promoter reporter assay Molecular and Cellular Biology High 20516212
2010 MEOX2 protein localizes to the nuclear fraction in vascular endothelial cells; MEOX2 physically interacts with both NF-κB p65 and IκBβ by co-immunoprecipitation; MEOX2 colocalizes with p65 and IκBβ in the nucleus; this colocalization requires the MEOX2 homeodomain and N-terminal domain; MEOX2 has a biphasic effect on NF-κB-dependent promoters (stimulatory at low levels, repressive at high levels). Subcellular fractionation, co-immunoprecipitation, immunofluorescence colocalization, promoter reporter assays with domain deletion mutants Cardiovascular Research High 20421348
2011 MEOX2 directly activates both p21CIP1/WAF1 and p16INK4a expression to induce endothelial cell cycle arrest and senescence; MEOX1 and MEOX2 activate p16INK4a in a DNA binding-dependent manner, whereas they induce p21CIP1/WAF1 in a DNA binding-independent manner, revealing mechanistically distinct modes of transcriptional activation for these two CDK inhibitor targets. Overexpression of MEOX1/MEOX2 and DNA-binding mutants, promoter reporter assays, cell cycle and senescence assays PLoS One High 22206000
2011 The miR-130/301/721 miRNA family enhances iPSC generation by targeting and repressing Meox2 (GAX); miRNA-resistant Meox2 overexpression abrogates the reprogramming effect of these miRNAs, and Meox2-specific silencing mimics their effects, demonstrating that Meox2 suppression is a key mechanism through which these miRNAs facilitate reprogramming. miRNA library screen in murine fibroblasts, miRNA-resistant Meox2 overexpression, Meox2-specific siRNA knockdown, iPSC formation assays EMBO Reports High 21941297
2013 MEOX2 overexpression shifts cardiac myofibroblasts back toward the fibroblast phenotype, but a MEOX2 DNA-binding mutant has no effect on myofibroblast phenotype, demonstrating a DNA-binding-dependent mechanism. Ski modulates myofibroblast phenotype through suppression of Zeb2, thereby upregulating Meox2 expression (Ski→↓Zeb2→↑Meox2→fibroblast phenotype). Meox2 overexpression and DNA-binding mutant, Ski overexpression, Western blot for Zeb2, phenotypic assays, cardiac scar tissue analysis Journal of Cell Science High 24155330
2015 Meox2/Tcf15 form heterodimers that function as transcriptional determinants of heart capillary endothelial cell identity; Meox2/Tcf15 drive endothelial CD36 and lipoprotein lipase expression to mediate fatty acid uptake in heart ECs and facilitate FA transport to cardiomyocytes. Combined Meox2/Tcf15 haplodeficiency impairs cardiac FA uptake and contractility. Microarray profiling of freshly isolated ECs, gain- and loss-of-function genetic approaches, combined haplodeficiency mouse model, cardiac contractility measurement Circulation High 25561514
2016 Meox2 haploinsufficiency in a mouse model of Alzheimer's disease increases neuronal cell loss in regions containing plaques and decreases plaque-associated microvessel density, supporting a synergistic effect of vascular compromise and amyloid deposition on neuronal dysfunction. Meox2 haploinsufficiency combined with APP/PS1 transgenic mouse model, histological analysis, microvessel quantification Neurobiology of Aging Medium 27143421
2022 MEOX2 enhances ERK signaling in glioblastoma through a feed-forward mechanism; Ser155 is a putative ERK-dependent phosphorylation site upstream of the homeodomain, and S155A substitution affects MEOX2 protein levels and alters its subnuclear localization. MEOX2 overexpression cooperates with p53 and PTEN loss to induce cell proliferation in cerebral organoid models. Constitutive knockdown/overexpression in patient-derived GBM tumorspheres, ERK phosphorylation assays by Western blot, S155A mutagenesis, cerebral organoid models, RNA-seq, ACT-seq, CUT&Tag for target gene identification Neuro-oncology High 35468210
2022 MEOX2 directly activates Cathepsin S (CTSS) transcription in glioma cells as demonstrated by ChIP-qPCR and luciferase reporter assay; MEOX2 promotes glioma cell proliferation, motility, EMT, focal adhesion formation, and F-actin assembly, partly through CTSS regulation. RNA-sequencing, ChIP-qPCR, luciferase reporter assay, MEOX2 knockdown/overexpression, in vivo mouse intracranial implantation model Cell Death & Disease High 35436995
2022 ABI2 directly interacts with MEOX2 by co-immunoprecipitation; MEOX2 binds to KLF4 and NANOG promoter regions to activate their transcription, maintaining cancer stem cell populations in HCC; MEOX2 overexpression restores ABI2 knockdown effects on malignant behavior. Co-immunoprecipitation, ChIP for MEOX2 binding to KLF4/NANOG promoters, functional rescue experiments, xenograft models Liver International High 36017822
2022 MEOX2 is involved in cell viability, proliferation, and adhesion of glioma stem-like cells through ERK/MAPK and PI3K/AKT pathways; MEOX2 loss of function correlates with GSC differentiation toward neuronal lineage characteristics and decreased pFAK with increased CDH10 expression. siRNA loss-of-function in GSCs, cell viability assays, Western blot for pathway components, differentiation assays Cancers Medium 34885053
2022 MEOX2 regulates genes of the glycolytic pathway and hypoxic response in glioblastoma stem-like cells; shRNA-mediated MEOX2 knockdown inhibits cell growth, sphere-forming ability, and increases apoptosis; in silico analysis identifies GC-rich Sp1 and Klf4 binding motifs in regulatory regions of MEOX2-regulated genes. shRNA knockdown in GSC lines, transcriptome analysis (RNA-seq), sphere-forming assay, apoptosis assay Cancers Medium 35565433
2022 MEOX2 and GLI1 epigenetically regulate EGFR gene expression in lung cancer by reducing repressive histone marks (EZH2/H3K27me3) and increasing activating marks (H3K27Ac/H3K4me3) at the EGFR gene enhancer-promoter sequences, contributing to EGFR-TKI resistance. shRNA silencing, ChIP-qPCR for histone modifications at EGFR locus, Western blot, in vivo tumor progression models European Journal of Cancer Medium 34844838
2022 MEOX2 modulates nociceptor function: MEOX2 is expressed in mouse dorsal root ganglia sensory neuron nuclei, and Meox2 heterozygosity impairs action potential initiation, correlating with decreased expression of Scn9a (Nav1.7) and Scn11a (Nav1.9) voltage-gated sodium channels. Transcriptomic analysis reveals downregulation of pain perception genes (PENK, NPY) in Meox2+/- DRG. Meox2 heterozygous mouse model, behavioral analysis, electrophysiology, immunofluorescence, transcriptomic analysis, qPCR FEBS Journal High 35029322
2023 RNF10 interacts with Meox2 and MEOX2 overexpression promotes Meox2 expression while inhibiting AP-1 in cardiomyocytes; overexpression of RNF10 in H9C2 cells significantly promotes Meox2, inhibits AP-1, alleviates apoptosis, and antagonizes pirarubicin-induced cardiotoxicity, demonstrating the AP-1/Meox2 signaling axis downstream of RNF10. siRNA and lentiviral overexpression of RNF10 in H9C2 cells, Western blot for Meox2 and AP-1, apoptosis assays, in vivo rat cardiotoxicity model Oxidative Medicine and Cellular Longevity Medium 36713029
2024 MEOX2 binds to the PHLPP promoter to upregulate its transcription (demonstrated by dual luciferase reporter assay), leading to inhibition of p-AKT expression and reduced HSC proliferation; MEOX2 overexpression inhibits hepatic stellate cell vitality and proliferation through the PHLPP/PI3K/AKT axis. Lentiviral OE and shRNA KD of MEOX2, dual luciferase reporter assay for MEOX2 binding to PHLPP promoter, Western blot for p-AKT, CCK-8 and EdU proliferation assays Discovery Medicine Medium 38926106
2025 NAT10-mediated ac4C RNA modification at nucleotides 409–423 of MEOX2 mRNA regulates MEOX2 mRNA stability and expression; NAT10 directly binds MEOX2 mRNA (demonstrated by RIP), and NAT10 silencing reduces ac4C modification and MEOX2 expression, promoting HUVEC migration, invasion, and angiogenesis. MEOX2 overexpression reverses the effects of NAT10 inhibition. MeRIP-qPCR, RNA immunoprecipitation, dual-luciferase reporter assay, RNA stability assay, functional cellular assays in HUVECs Applied Biochemistry and Biotechnology Medium 41082000
2025 MEOX2 interacts with PARP1 (identified by co-immunoprecipitation and mass spectrometry) in glioblastoma stem-like cells; MEOX2 depletion reduces PARylation levels, impairs DNA repair, and increases sensitivity to the PARP1 inhibitor Talazoparib. MEOX2 knockdown impairs tumor growth and increases temozolomide sensitivity in a GLICO (cerebral organoid) model. Co-immunoprecipitation, mass spectrometry, PARylation assays, PARP inhibitor sensitivity, GLICO tumor organoid model, DNA damage assays Cancer Letters High 41620199

Source papers

Stage 0 corpus · 95 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2007 Regulation of angiogenesis through a microRNA (miR-130a) that down-regulates antiangiogenic homeobox genes GAX and HOXA5. Blood 386 17957028
1992 Mox-1 and Mox-2 define a novel homeobox gene subfamily and are differentially expressed during early mesodermal patterning in mouse embryos. Development (Cambridge, England) 263 1363541
2005 Role of the MEOX2 homeobox gene in neurovascular dysfunction in Alzheimer disease. Nature medicine 243 16116430
1997 p21CIP1-mediated inhibition of cell proliferation by overexpression of the gax homeodomain gene. Genes & development 155 9224717
1999 Mox2 is a component of the genetic hierarchy controlling limb muscle development. Nature 150 10403250
1995 Expression of gax, a growth arrest homeobox gene, is rapidly down-regulated in the rat carotid artery during the proliferative response to balloon injury. The Journal of biological chemistry 85 7890661
2015 Meox2/Tcf15 heterodimers program the heart capillary endothelium for cardiac fatty acid uptake. Circulation 84 25561514
2010 Intronic miR-301 feedback regulates its host gene, ska2, in A549 cells by targeting MEOX2 to affect ERK/CREB pathways. Biochemical and biophysical research communications 80 20470754
2011 miRNA screening reveals a new miRNA family stimulating iPS cell generation via regulation of Meox2. EMBO reports 75 21941297
2010 Regulation of the expression and activity of the antiangiogenic homeobox gene GAX/MEOX2 by ZEB2 and microRNA-221. Molecular and cellular biology 74 20516212
1999 Regulation of smooth muscle cell migration and integrin expression by the Gax transcription factor. The Journal of clinical investigation 69 10562309
2012 miR-301a is a candidate oncogene that targets the homeobox gene Gax in human hepatocellular carcinoma. Digestive diseases and sciences 64 22373864
2003 Inhibition of endothelial cell activation by the homeobox gene Gax. The Journal of surgical research 62 12842453
2011 Mechanisms of MEOX1 and MEOX2 regulation of the cyclin dependent kinase inhibitors p21 and p16 in vascular endothelial cells. PloS one 58 22206000
1997 Percutaneous delivery of the gax gene inhibits vessel stenosis in a rabbit model of balloon angioplasty. Cardiovascular research 57 9415299
2021 Tumor-derived exosomal miRNA-141 promote angiogenesis and malignant progression of lung cancer by targeting growth arrest-specific homeobox gene (GAX). Bioengineered 48 33627047
1998 Bax-mediated cell death by the Gax homeoprotein requires mitogen activation but is independent of cell cycle activity. The EMBO journal 46 9649428
2020 MiR-148a-3p Regulates Skeletal Muscle Satellite Cell Differentiation and Apoptosis via the PI3K/AKT Signaling Pathway by Targeting Meox2. Frontiers in genetics 45 32582277
2013 The Ski-Zeb2-Meox2 pathway provides a novel mechanism for regulation of the cardiac myofibroblast phenotype. Journal of cell science 40 24155330
2006 Analysis of Meox-2 mutant mice reveals a novel postfusion-based cleft palate. Developmental dynamics : an official publication of the American Association of Anatomists 40 16284941
1996 Differential localization of Mox-1 and Mox-2 proteins indicates distinct roles during development. The International journal of developmental biology 40 9032023
1999 Adenovirus-mediated delivery of the Gax transcription factor to rat carotid arteries inhibits smooth muscle proliferation and induces apoptosis. Gene therapy 39 10505098
2000 Effect of percutaneous adenovirus-mediated Gax gene delivery to the arterial wall in double-injured atheromatous stented rabbit iliac arteries. Gene therapy 38 10981661
1995 Regulation of Gax homeobox gene transcription by a combination of positive factors including myocyte-specific enhancer factor 2. Molecular and cellular biology 36 7623821
2007 A comparative analysis of Meox1 and Meox2 in the developing somites and limbs of the chick embryo. The International journal of developmental biology 34 17939123
2001 Homeodomain proteins Mox1 and Mox2 associate with Pax1 and Pax3 transcription factors. FEBS letters 34 11423130
2000 The homeobox genes MSX2 and MOX2 are candidates for regulating epithelial-mesenchymal cell interactions in the human placenta. Placenta 34 10831122
2006 The homeobox gene GAX activates p21WAF1/CIP1 expression in vascular endothelial cells through direct interaction with upstream AT-rich sequences. The Journal of biological chemistry 33 17074759
2022 ABI2-mediated MEOX2/KLF4-NANOG axis promotes liver cancer stem cell and drives tumour recurrence. Liver international : official journal of the International Association for the Study of the Liver 32 36017822
2008 Cross talk among Smad, MAPK, and integrin signaling pathways enhances adventitial fibroblast functions activated by transforming growth factor-beta1 and inhibited by Gax. Arteriosclerosis, thrombosis, and vascular biology 32 18187669
1997 Embryonic expression of the Gax homeodomain protein in cardiac, smooth, and skeletal muscle. Circulation research 32 9118475
1997 Opposite regulation of Gax homeobox expression by angiotensin II and C-type natriuretic peptide. Hypertension (Dallas, Tex. : 1979) 31 9039131
2009 Two candidate tumor suppressor genes, MEOX2 and SOSTDC1, identified in a 7p21 homozygous deletion region in a Wilms tumor. Genes, chromosomes & cancer 30 19760604
2007 Functional role of Meox2 during the epithelial cytostatic response to TGF-beta. Molecular oncology 28 19383287
2010 Involvement of Gax gene in hypoxia-induced pulmonary hypertension, proliferation, and apoptosis of arterial smooth muscle cells. American journal of respiratory cell and molecular biology 27 20160044
2022 MEOX2 homeobox gene promotes growth of malignant gliomas. Neuro-oncology 26 35468210
2021 Exosomal circular RNA circ_0074673 regulates the proliferation, migration, and angiogenesis of human umbilical vein endothelial cells via the microRNA-1200/MEOX2 axis. Bioengineered 26 34516311
2017 Gax suppresses chemerin/CMKLR1-induced preadipocyte biofunctions through the inhibition of Akt/mTOR and ERK signaling pathways. Journal of cellular physiology 26 28326537
2016 Meox2 haploinsufficiency increases neuronal cell loss in a mouse model of Alzheimer's disease. Neurobiology of aging 26 27143421
2014 Involvement of IGF-1 and MEOX2 in PI3K/Akt1/2 and ERK1/2 pathways mediated proliferation and differentiation of perivascular adipocytes. Experimental cell research 26 25239227
2010 MEOX2 regulates nuclear factor-kappaB activity in vascular endothelial cells through interactions with p65 and IkappaBbeta. Cardiovascular research 26 20421348
2009 A functional screen for regulators of CKDN2A reveals MEOX2 as a transcriptional activator of INK4a. PloS one 25 19340300
1997 Forced expression of the homeodomain protein Gax inhibits cardiomyocyte proliferation and perturbs heart morphogenesis. Development (Cambridge, England) 25 9334288
1995 The expression pattern of Xenopus Mox-2 implies a role in initial mesodermal differentiation. Mechanisms of development 24 7577672
2018 Over-expression of MEOX2 promotes apoptosis through inhibiting the PI3K/Akt pathway in laryngeal cancer cells. Neoplasma 22 29940775
2005 Characterization of Mesenchyme Homeobox 2 (MEOX2) transcription factor binding to RING finger protein 10. Molecular and cellular biochemistry 22 16335786
2014 Regulatory specialization of xyloglucan (XG) and glucuronoarabinoxylan (GAX) in pericarp cell walls during fruit ripening in tomato (Solanum lycopersicum). PloS one 21 24587088
1995 Isolation of the human MOX2 homeobox gene and localization to chromosome 7p22.1-p21.3. Genomics 18 7607679
2022 MEOX2-mediated regulation of Cathepsin S promotes cell proliferation and motility in glioma. Cell death & disease 17 35436995
2010 Gax gene transfer inhibits vascular remodeling induced by adventitial inflammation in rabbits. Atherosclerosis 17 20598309
1994 Molecular cloning and localization of the human GAX gene to 7p21. Genomics 17 7713505
2017 Role of microRNA-130a in the pathogeneses of obstructive sleep apnea hypopnea syndrome-associated pulmonary hypertension by targeting the GAX gene. Medicine 16 28514291
2021 MicroRNA-301a-3p promotes triple-negative breast cancer progression through downregulating MEOX2. Experimental and therapeutic medicine 14 34306209
2021 Failure to EGFR-TKI-based therapy and tumoural progression are promoted by MEOX2/GLI1-mediated epigenetic regulation of EGFR in the human lung cancer. European journal of cancer (Oxford, England : 1990) 14 34844838
1998 Characterization and localization of Mox2, the gene encoding the murine homolog of the rat MRC OX-2 membrane glycoprotein. Mammalian genome : official journal of the International Mammalian Genome Society 14 9457671
2005 Angiotensin II suppresses growth arrest specific homeobox (Gax) expression via redox-sensitive mitogen-activated protein kinase (MAPK). Regulatory peptides 12 15680482
2020 Facilitation of Bone Healing Processes Based on the Developmental Function of Meox2 in Tooth Loss Lesion. International journal of molecular sciences 11 33218046
2016 Gax regulates human vascular smooth muscle cell phenotypic modulation and vascular remodeling. American journal of translational research 11 27508012
1996 Growth-arrest homeobox gene Gax: a molecular strategy to prevent arterial restenosis. Schweizerische medizinische Wochenschrift 11 8893412
2021 The promotion of cervical cancer progression by signal transducer and activator of transcription 1-induced up-regulation of lncRNA MEOX2-AS1 as a competing endogenous RNA through miR-143-3p/VDAC1 pathway. Bioengineered 9 34224325
2021 MEOX2 Transcription Factor Is Involved in Survival and Adhesion of Glioma Stem-like Cells. Cancers 9 34885053
2014 Ski diminishes TGF-β1-induced myofibroblast phenotype via up-regulating Meox2 expression. Experimental and molecular pathology 9 25445500
2022 MEOX2 Regulates the Growth and Survival of Glioblastoma Stem Cells by Modulating Genes of the Glycolytic Pathway and Response to Hypoxia. Cancers 7 35565433
2021 MEOX2 serves as a novel biomarker associated with macrophage infiltration in oesophageal squamous cell carcinoma and other digestive system carcinomas. Autoimmunity 7 34160343
2023 circINSR Inhibits Adipogenic Differentiation of Adipose-Derived Stromal Vascular Fractions through the miR-152/MEOX2 Axis in Sheep. International journal of molecular sciences 6 36834919
2022 Transcription factor mesenchyme homeobox protein 2 (MEOX2) modulates nociceptor function. The FEBS journal 6 35029322
2019 Meox2 Haploinsufficiency Accelerates Axonal Degeneration in DBA/2J Glaucoma. Investigative ophthalmology & visual science 6 31369031
2014 Overexpression of the growth arrest-specific homeobox gene Gax inhibits proliferation, migration, cell cycle progression, and apoptosis in serum-induced vascular smooth muscle cells. Genetics and molecular research : GMR 6 24737425
2014 Gax inhibits perivascular preadipocyte biofunction mediated by IGF-1 induced FAK/Pyk2 and ERK2 cooperative pathways. Cellular signalling 6 25280940
2006 Down-regulation of the gax gene in smooth muscle cells of the splenic vein of portal hypertension patients. Hepatobiliary & pancreatic diseases international : HBPD INT 6 16698584
2001 Isolation of the avian homologue of the homeobox gene Mox2 and analysis of its expression pattern in developing somites and limbs. Mechanisms of development 6 11404088
2023 The miR-148/152 family contributes to angiogenesis of human pluripotent stem cell- derived endothelial cells by inhibiting MEOX2. Molecular therapy. Nucleic acids 5 37200858
2023 Diagnostic Utility of Immunohistochemical Detection of MEOX2, SOX11, INSM1 and EGFR in Gliomas. Diagnostics (Basel, Switzerland) 5 37568909
2017 Association of MEOX2 polymorphism with nonsyndromic cleft palate only in a Vietnamese population. Congenital anomalies 5 29030958
2022 A Crucial Angiogenesis-Associated Gene MEOX2 Could Be a Promising Biomarker Candidate for Breast Cancer. Frontiers in oncology 4 35615155
2015 Activation of Transcription Factor GAX and Concomitant Downregulation of IL-1β and ERK1/2 Modulate Vascular Smooth Muscle Cell Phenotype in 3D Fibrous Scaffolds. Tissue engineering. Part A 4 26041434
2022 Fabrication of High-Performance Solar Cells and X-ray Detectors Using MoX2@CNT Nanocomposite-Tuned Perovskite Layers. ACS applied materials & interfaces 3 35834414
2024 MEOX2 Participates in Hepatic Stellate Cells-Induced Liver Fibrosis by Regulating the PI3K/AKT Signaling Pathway. Discovery medicine 2 38926106
2023 RING Finger Protein 10 Regulates AP-1/Meox2 to Mediate Pirarubicin-Induced Cardiomyocyte Apoptosis. Oxidative medicine and cellular longevity 2 36713029
2018 Generation of induced pluripotent stem cell line (ZZUi0013-A) from a 65-year-old patient with a novel MEOX2 gene mutation in Alzheimer's disease. Stem cell research 2 30616143
2025 SMARCB1-driven EGFR-GLI1 epigenetic alterations in lung cancer progression and therapy are differentially modulated by MEOX2 and GLI-1. Cancer gene therapy 1 39971779
2025 MEOX2 mediates cisplatin resistance in ovarian cancer via E2F target and DNA repair pathways. Journal of ovarian research 1 40119426
2025 Circ_0000190 inhibits the progression of triple negative breast cancer by regulating miR-301a/MEOX2 pathway. American journal of cancer research 1 40371159
2025 NAT10 Regulates the Migration, Invasion, and Angiogenesis of Human Umbilical Vein Endothelial Cells Through ac4C Modification of MEOX2 in Gestational Diabetes Mellitus. Applied biochemistry and biotechnology 1 41082000
2023 Ring finger protein 10 improves pirarubicin-induced cardiac inflammation by regulating the AP-1/Meox2 signaling pathway. Toxicology and applied pharmacology 1 36740146
2026 MEOX2 enhances DNA repair and therapy resistance in Glioblastoma stem-like cells via PARP1 interaction. Cancer letters 0 41620199
2026 CircEif3c/miR-96-5p/PHF20L1/MEOX2 axis in perivascular preadipocyte exosomes mediates fibroblast dysfunction and vascular remodeling. Non-coding RNA research 0 41809968
2025 Overexpression of MEOX2 inhibits breast cancer cell metastasis by targeting oxidative stress-induced RGS5. In vitro cellular & developmental biology. Animal 0 40603753
2024 The structural, stability, electronic, optical and thermodynamic properties of MoX2 (X= S, Se, and Te) under hydrostatic pressures: a plasmon approach and first-principle study. Journal of molecular modeling 0 38462593
2018 Investigation of Surface Sulfurization in CuIn1-x Gax S2-y Sey Thin Films by Using Kelvin Probe Force Microscopy. Chemphyschem : a European journal of chemical physics and physical chemistry 0 29143420
2012 [Effects on proliferation and apoptosis of serum-induced rabbit VSMCs by adenovirus-mediated transfer of the Gax gene]. Xi bao yu fen zi mian yi xue za zhi = Chinese journal of cellular and molecular immunology 0 22230501
2011 [Construction of human Gax gene eukaryotic expression vector and its expression in vascular smooth muscle cells]. Xi bao yu fen zi mian yi xue za zhi = Chinese journal of cellular and molecular immunology 0 21208560
2009 [Negative regulation of cells proliferation by Gax gene and its mechanisms]. Sheng wu yi xue gong cheng xue za zhi = Journal of biomedical engineering = Shengwu yixue gongchengxue zazhi 0 19334588
2007 [Effect of Ad-Gax transfection on apoptosis of human lung adenocarcinoma A549 cells and its mechanism]. Zhongguo fei ai za zhi = Chinese journal of lung cancer 0 21122291
2006 [Effects of Gax gene transfection on proliferation and expression of proto-oncogenes in A549 cells]. Zhongguo fei ai za zhi = Chinese journal of lung cancer 0 21172149