Affinage

MTA1

Metastasis-associated protein MTA1 · UniProt Q13330

Length
715 aa
Mass
80.8 kDa
Annotated
2026-06-10
100 papers in source corpus 35 papers cited in narrative 35 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

MTA1 is the scaffold subunit of the NuRD (nucleosome remodeling and deacetylase) complex and a multifunctional chromatin-associated coregulator that controls transcription, genome stability, and tumor progression (PMID:24920672, PMID:32901005). As a NuRD scaffold it binds RbAp46/48 (RBBP4/7) — using the same RbAp48 surface that engages histone H4, and accommodating two RBBP4 molecules — to integrate these subunits into the complex, and it can assemble a minimal MTA1-HDAC1-RBBP4/7 subcomplex (M1HR) recruited to H2A.Z chromatin by PWWP2A (PMID:24920672, PMID:27144666, PMID:30327463). Through this machinery MTA1 acts predominantly as an HDAC-dependent transcriptional corepressor, binding target promoters and recruiting HDAC1/2 to deacetylate histones; it represses MMP-9 (also via HDAC-independent Mi2/remodeling activity), BRCA1, p21WAF1, and SMAD7, and antagonizes estrogen receptor signaling by sequestering coactivators such as MICoA and inhibiting CAK-mediated ERα phosphorylation (PMID:12431981, PMID:17922032, PMID:20071335, PMID:22841502, PMID:12639951, PMID:12527756). MTA1 also functions as a context-dependent transcriptional activator: acetylation on Lys626 enables p300 binding and RNA Pol II recruitment to drive BCAS3 and Pax5, and it forms coactivator complexes with STAT3, c-Myc, and NF-κB/p65RelA to induce STAT3 targets, LDHA, and inflammatory genes (PMID:16617102, PMID:17671180, PMID:23580571, PMID:31570164, PMID:20702415). A cytoplasmic short isoform (MTA1s) bearing an LRILL motif sequesters ERα in the cytoplasm to enhance non-genomic estrogen signaling (PMID:12167865). MTA1 supports genome integrity by stabilizing HIF-1α through deacetylation, controlling p53 stability and p53R2-dependent repair, coupling to ATR-Claspin-Chk1 checkpoint signaling, and regulating alternative splicing of mitosis regulators to prevent chromosomal instability (PMID:18264140, PMID:19837670, PMID:20427275, PMID:32901005). Its abundance and activity are tuned by COP1-mediated ubiquitin-proteasome degradation (disrupted by ionizing radiation), p53-PARP1-driven transcriptional repression, SUMO2/3 conjugation at Lys509, and O-GlcNAcylation, the latter enhancing chromatin and NuRD association (PMID:19805145, PMID:22286760, PMID:21965678, PMID:34019948).

Mechanistic history

Synthesis pass · year-by-year structured walk · 21 steps
  1. 2001 Medium

    Established the determinants of MTA1 subcellular targeting, showing nuclear localization is encoded by C-terminal signals while distinct ligand motifs link it to cytoplasmic signaling adaptors.

    Evidence GFP-tagged deletion constructs and Co-IP in mouse Mta1, mapping NLS and SH3 ligand sites and Grb2/Fyn binding

    PMID:11483358

    Open questions at the time
    • Human MTA1 not directly tested
    • Functional consequence of Grb2/Fyn binding for transcription unresolved
  2. 2002 High

    Defined a non-genomic mode of MTA1 action: a cytoplasmic short isoform directly sequesters ERα to redirect estrogen signaling, answering how MTA1 overexpression dysregulates hormone responses downstream of HER2.

    Evidence Motif-deletion mutagenesis, fractionation/IF, and Co-IP of MTA1s-ERα in breast cancer cells

    PMID:12167865

    Open questions at the time
    • Relative abundance of MTA1s vs full-length in tumors not quantified
    • Does not address nuclear NuRD functions
  3. 2002 High

    Showed MTA1 represses a metastasis-relevant gene through dual chromatin mechanisms, establishing that its corepressor activity is only partly HDAC-dependent.

    Evidence ChIP, Co-IP, DNase I hypersensitivity, and TSA treatment at the MMP-9 promoter

    PMID:12431981

    Open questions at the time
    • Precise contribution of Mi2 remodeling vs HDAC not quantified
    • In vivo relevance to invasion not tested here
  4. 2003 High

    Identified the mechanistic basis of MTA1 antagonism of estrogen signaling — direct interception of coactivator (MICoA) and the ERα-activating kinase (CAK/MAT1).

    Evidence Yeast two-hybrid, in vitro/in vivo binding, kinase and reporter assays

    PMID:12527756 PMID:12639951

    Open questions at the time
    • Endogenous stoichiometry of competing complexes unknown
    • Generalizability beyond ER targets untested
  5. 2006 High

    Reversed the corepressor-only view by showing acetylation of MTA1 at Lys626 licenses it to recruit RNA Pol II and activate transcription, defining a PTM switch for coactivator function.

    Evidence ChIP, acetylation-site mutagenesis, reporter assay, and transgenic mouse at the BCAS3 locus

    PMID:16617102

    Open questions at the time
    • Acetyltransferase responsible not fully defined here
    • How acetylation alters complex composition unresolved
  6. 2007 High

    Extended the coactivator/corepressor duality to oncogenic targets, linking acetylated MTA1-p300 to Pax5 activation and MTA1-NuRD to BRCA1 repression with a genome-instability phenotype.

    Evidence ChIP, Co-IP, transgenic mouse, and centrosome amplification rescue assays

    PMID:17671180 PMID:17922032

    Open questions at the time
    • Determinants selecting activation vs repression at a given promoter unclear
    • BRCA1 repression in non-breast contexts untested
  7. 2008 High

    Connected MTA1 to hypoxic signaling, showing the MTA1/HDAC complex deacetylates HIF-1α to block its VHL-mediated degradation.

    Evidence Reciprocal Co-IP, siRNA knockdown, and HBx-transgenic mouse

    PMID:18264140

    Open questions at the time
    • HBx-independent HIF-1α regulation not fully resolved
    • Specific HIF-1α lysines deacetylated not mapped
  8. 2009 High

    Placed MTA1 within the ubiquitin-proteasome and p53 networks, defining a COP1-MTA1 degradation/feedback loop and MTA1's stabilization of p53 to drive DNA-repair gene expression.

    Evidence Ubiquitination assays, COP1 RING mutants, Co-IP, ChIP, and DNA repair assays

    PMID:19805145 PMID:19837670

    Open questions at the time
    • Quantitative balance of MTA1's p53-stabilizing vs corepressor roles unclear
    • In vivo physiological setting of the COP1 loop not established
  9. 2010 High

    Established MTA1 as a checkpoint and repair effector — repressing p21WAF1 independently of p53 and acting downstream of ATR to sustain Chk1/Claspin and the G2-M checkpoint.

    Evidence ChIP and siRNA in p53-null cells, Co-IP of MTA1-ATR, γH2AX focus and cell-cycle assays

    PMID:20071335 PMID:20427275

    Open questions at the time
    • Direct enzymatic role of MTA1 in repair vs scaffolding unresolved
    • Mechanism of UV-induced MTA1 stabilization beyond ATR unclear
  10. 2010 High

    Revealed an immune/inflammatory function, showing MTA1 is required as a coactivator at NF-κB-driven promoters (MyD88, TG2) in LPS-stimulated macrophages.

    Evidence ChIP, siRNA, NF-κB inhibitor treatment, and cytokine/target gene readouts

    PMID:20702415 PMID:21156794

    Open questions at the time
    • Mechanism of MTA1 switching to coactivation at NF-κB sites unclear
    • In vivo inflammatory phenotype not established here
  11. 2011 High

    Defined SUMOylation as a regulatory layer, mapping SUMO2/3 conjugation at Lys509 and a C-terminal SIM that together tune corepressor activity.

    Evidence In vivo SUMOylation assays, K509 mutagenesis, PIAS/SENP manipulation, ChIP, reporter assays

    PMID:21965678

    Open questions at the time
    • Signals controlling MTA1 SUMOylation dynamics unknown
    • Genome-wide impact of SUMO state not mapped
  12. 2012 Medium

    Closed a regulatory circuit by showing p53 transcriptionally represses MTA1 via PARP-1-dependent poly(ADP-ribosyl)ation, and demonstrated MTA1-NuRD repression of SMAD7 in TGF-β signaling.

    Evidence ChIP, promoter proteomics, p53 WT/null comparison, PARP-1 inhibition; ChIP/shRNA at SMAD7

    PMID:22286760 PMID:22841502

    Open questions at the time
    • SMAD7 finding limited to single-lab ChIP/knockdown
    • Conditions favoring p53 repression of MTA1 in vivo unclear
  13. 2013 High

    Identified MTA1 as a selective metastasis modifier acting through an MTA1/STAT3/Pol II coactivator complex to induce Twist1, dissociating metastatic from primary-tumor functions.

    Evidence Genetic MTA1 depletion in a spontaneous mouse breast cancer model, Co-IP, ChIP

    PMID:23580571

    Open questions at the time
    • Determinants of MTA1-STAT3 complex assembly unclear
    • Relative contribution of STAT3 vs other axes to metastasis not quantified
  14. 2014 High

    Provided the structural and architectural basis for NuRD assembly, showing MTA1 scaffolds RbAp46/48 by occluding the histone-H4-binding surface and binds two RBBP4 molecules.

    Evidence Crystal structure of RbAp48-MTA1, in vitro binding, in vivo assembly assays; negative-stain EM and crosslinking MS

    PMID:24920672 PMID:27144666

    Open questions at the time
    • Full NuRD architecture not resolved at high resolution
    • How scaffold occupancy gates histone engagement in vivo untested
  15. 2014 Medium

    Broadened MTA1's role beyond NuRD to direct chromatin organization, showing it decondenses chromatin independently of Mi-2 and modulates H1-chromatin interaction, plus a domain-dependent multi-compartment localization.

    Evidence Live-cell imaging, FRAP, chromatin fractionation; IF/fractionation with differentiation assays

    PMID:24970816 PMID:25205035

    Open questions at the time
    • Single-lab findings without orthogonal confirmation
    • Molecular basis of MTA1-driven decondensation unresolved
  16. 2017 Medium

    Mechanistically linked MTA1 to EMT and invasion via target programs — inducing miR-22 to repress E-cadherin and activating ErbB2 transcription with HDAC2.

    Evidence 3'-UTR luciferase reporter, ChIP, Co-IP, loss/gain-of-function, in vivo tumor model

    PMID:28231399 PMID:28288133

    Open questions at the time
    • Single-lab studies with limited orthogonal validation
    • Whether these axes operate together in the same tumors unclear
  17. 2018 High

    Defined a targeting mechanism for a minimal MTA1 subcomplex, showing PWWP2A directs M1HR (MTA1-HDAC1-RBBP4/7) to H2A.Z chromatin for deacetylation.

    Evidence AP-MS, Co-IP, ChIP-seq, and siRNA with histone acetylation readout

    PMID:30327463

    Open questions at the time
    • Relationship between M1HR and canonical NuRD in cells unclear
    • Genome-wide functional outcome of M1HR loss not fully mapped
  18. 2019 Medium

    Expanded MTA1 into metabolic and extracellular/paracrine roles — c-Myc-dependent LDHA activation, autophagy/AMPK-driven tamoxifen resistance, VEGFR2-mediated phosphorylation with extracellular pro-angiogenic activity, and exosomal intercellular transfer.

    Evidence ChIP/Co-IP at LDHA; autophagy flux and ATG7 knockdown; recombinant MTA1 angiogenesis assays; CRISPR KO and exosome tracking with reporters

    PMID:24265228 PMID:29130361 PMID:30782165 PMID:31570164

    Open questions at the time
    • Each axis from a single lab with limited replication
    • Physiological levels of extracellular/exosomal MTA1 not established
  19. 2020 High

    Discovered an RNA-level function, showing MTA1 directly binds transcripts and regulates alternative splicing of mitosis regulators, with loss causing chromosomal instability.

    Evidence fCLIP-seq, RNA-seq, siRNA/KO, and chromosome segregation/CIN assays

    PMID:32901005

    Open questions at the time
    • Direct RNA-binding domain of MTA1 not defined
    • Relationship between RNA-binding and chromatin functions unresolved
  20. 2021 Medium

    Added O-GlcNAcylation as a chromatin-targeting PTM, mapping S237/S241/S246 modification that enhances MTA1 chromatin and NuRD association and reprograms target genes in drug-resistant cells.

    Evidence Quantitative MS site mapping, ChIP-seq, transcriptomics, and OGT manipulation

    PMID:34019948

    Open questions at the time
    • Single-lab study
    • Signaling controlling MTA1 O-GlcNAcylation unclear
  21. 2022 Medium

    Revealed higher-order repressive complex assembly and isoform-level control, showing RUNX2 recruits MTA1/NuRD with CRL4B to couple deacetylation and ubiquitylation, and that RALY/SF3B3-driven MTA1 splicing controls proliferation.

    Evidence Co-IP, ChIP-seq, genome-wide target analysis, bone metastasis xenografts; splicing assays with RALY/SF3B3 manipulation and pathway readouts

    PMID:35490918 PMID:35534547

    Open questions at the time
    • Generality of RUNX2/NuRD/CRL4B complex beyond breast cancer unclear
    • Isoform-switch mechanism single-lab

Open questions

Synthesis pass · forward-looking unresolved questions
  • How MTA1's competing corepressor versus coactivator states, RNA-binding versus chromatin functions, and the array of PTMs (acetylation, SUMO, O-GlcNAc) are integrated to specify a given target at a given locus remains unresolved.
  • No unified model linking PTM state to activator/repressor choice
  • Direct RNA-binding determinants undefined
  • High-resolution architecture of full NuRD lacking

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 6 GO:0003677 DNA binding 3 GO:0060090 molecular adaptor activity 3 GO:0098772 molecular function regulator activity 3 GO:0003723 RNA binding 1 GO:0140096 catalytic activity, acting on a protein 1
Localization
GO:0005634 nucleus 3 GO:0005829 cytosol 2 GO:0000228 nuclear chromosome 1 GO:0005635 nuclear envelope 1 GO:0005886 plasma membrane 1
Pathway
R-HSA-74160 Gene expression (Transcription) 5 R-HSA-73894 DNA Repair 4 R-HSA-162582 Signal Transduction 3 R-HSA-1643685 Disease 3 R-HSA-392499 Metabolism of proteins 3 R-HSA-4839726 Chromatin organization 3 R-HSA-8953854 Metabolism of RNA 1
Partners
ATRCOP1HDAC1HDAC2MYCRBBP4RBBP7STAT3
Complex memberships
M1HR (MTA1-HDAC1-RBBP4/7) subcomplexNuRD complex

Evidence

Reading pass · 35 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2002 A naturally occurring short isoform of MTA1 (MTA1s) contains a unique 33-amino-acid sequence with an ER-binding motif (LRILL). MTA1s localizes in the cytoplasm, sequesters ERα in the cytoplasm via this LRILL motif, and enhances non-genomic ER responses. Deletion of the LRILL motif abolishes MTA1s co-repressor function and its interaction with ERα, and restores nuclear localization of ERα. HER2 dysregulation in breast cancer cells enhances MTA1s expression and cytoplasmic ERα sequestration. Domain deletion mutagenesis, subcellular fractionation/immunofluorescence, Co-IP, ectopic expression in breast cancer cells Nature High 12167865
2002 MTA1 represses MMP-9 (92-kDa type IV collagenase) expression by binding to the distal MMP-9 promoter region and recruiting HDAC2, leading to diminished histone H3/H4 acetylation. MTA1 also recruits the nucleosome-remodeling Mi2 activity to the proximal promoter region. Trichostatin A only partially relieves MTA1-mediated repression, indicating both HDAC-dependent and HDAC-independent (Mi2-dependent) mechanisms. Chromatin immunoprecipitation (ChIP), Co-IP, DNase I hypersensitivity assay, forced expression, TSA treatment The Journal of biological chemistry High 12431981
2003 MTA1 interacts with MICoA (MTA1-interacting coactivator), identified by yeast two-hybrid screening. MICoA binds to the C-terminal region of MTA1 via an LSRLL nuclear receptor interaction motif, and the interaction was confirmed in vitro and in vivo. MTA1 represses MICoA-stimulated ERα transactivation and interferes with MICoA's association with ER-target gene promoter chromatin. Yeast two-hybrid, in vitro binding, Co-IP, chromatin immunoprecipitation, reporter assay The Journal of biological chemistry High 12639951
2003 MTA1 interacts with MAT1, an assembly/targeting factor for cyclin-dependent kinase-activating kinase (CAK). MTA1 binds the N-terminal RING finger domain of MAT1 via two MTA1 domains (C-terminal GATA domain and N-terminal bromo-domain). MTA1 inhibits CAK-stimulated ERα transactivation and inhibits CAK-mediated phosphorylation of ERα, partly through HDAC recruitment. Yeast two-hybrid, Co-IP (in vitro and in vivo), reporter assay, kinase assay, TSA treatment The Journal of biological chemistry High 12527756
2006 MTA1 acts as a transcriptional activator of BCAS3, a gene amplified in breast cancers. MTA1 stimulation of BCAS3 transcription requires ERα and an ERE half-site in the BCAS3 locus. MTA1 is acetylated on Lys626, and this acetylation is necessary for productive recruitment of RNA polymerase II complex to the BCAS3 enhancer. Functional genomic/chromatin screen, ChIP, reporter assay, site-directed mutagenesis of acetylation site, transgenic mouse model Proceedings of the National Academy of Sciences of the United States of America High 16617102
2007 MTA1-NuRD complex transcriptionally represses BRCA1 by physically associating with an atypical estrogen-responsive element (ERE) on the BRCA1 promoter in an ERα-dependent manner, recruiting HDAC. MTA1 overexpression causes centrosome amplification (a BRCA1 repression phenotype), reversible by BRCA1 re-expression. ChIP, Co-IP, siRNA knockdown, HDAC inhibitor (TSA) treatment, centrosome amplification assay, rescue experiment Oncogene High 17922032
2007 MTA1 acetylated on Lys626 interacts with p300 histone acetyltransferase and is recruited to the Pax5 promoter to stimulate Pax5 transcription, identified as a target driving B-cell lymphomagenesis in MTA1-transgenic mice. ChIP, Co-IP, gene expression profiling, transgenic mouse model Cancer research High 17671180
2008 MTA1 and HDAC1/2 physically associate with HIF-1α in the presence of HBx (hepatitis B virus X protein). MTA1/HDAC complex deacetylates the oxygen-dependent degradation domain of HIF-1α, leading to dissociation of prolyl hydroxylases and VHL from HIF-1α and thereby stabilizing HIF-1α. Knockdown of MTA1 abolishes this HBx-induced HIF-1α stabilization. Co-IP in vivo, siRNA knockdown, immunoprecipitation, HBx-transgenic mouse Oncogene High 18264140
2009 MTA1 is an ubiquitinated protein targeted by the RING-finger E3 ligase COP1 for degradation via the ubiquitin-proteasome pathway. Wild-type COP1 but not RING motif mutants promotes MTA1 ubiquitination and degradation. MTA1 in turn destabilizes COP1 by promoting COP1 autoubiquitination, creating a feedback loop. Ionizing radiation disrupts COP1-mediated MTA1 proteolysis, stabilizing MTA1 and promoting DNA double-strand break repair. Ubiquitination assay, proteasome inhibition, COP1 RING mutant expression, siRNA knockdown, Co-IP, DNA damage (IR) assay Proceedings of the National Academy of Sciences of the United States of America High 19805145
2009 MTA1 controls p53 stability by competing with COP1 to bind p53 and/or destabilizing COP1 and Mdm2, thereby inhibiting p53 ubiquitination. MTA1 regulates p53-dependent transcription of p53R2 (required for DNA repair). MTA1 depletion impairs p53-dependent p53R2 transcription and DNA repair, reversible by MTA1 re-introduction. Co-IP, ubiquitination assay, siRNA knockdown, ChIP, reporter assay, DNA repair assay The Journal of biological chemistry High 19837670
2010 MTA1 is a p53-independent transcriptional corepressor of p21WAF1. The mechanism involves recruitment of MTA1-HDAC2 complexes onto two selective regions of the p21WAF1 promoter. MTA1 depletion superinduces p21WAF1 even in p53-null cells, increases p21WAF1 binding to PCNA, and decreases nuclear PCNA accumulation after ionizing radiation. MTA1 expression in p53-null cells inhibits p21WAF1 promoter activity and increases DNA DSB repair. ChIP, siRNA knockdown in p53-null cells, reporter assay, Co-IP, gamma-H2AX focus assay, PCNA interaction assay The Journal of biological chemistry High 20071335
2010 UV radiation stabilizes MTA1 in an ATR-dependent manner and increases MTA1 binding to ATR. MTA1 depletion compromises ATR-mediated Chk1 activation by down-regulating Chk1 and its adaptor Claspin, and decreases gamma-H2AX induction and focus formation after UV treatment. MTA1 deficiency causes defective G2-M checkpoint and increased cellular sensitivity to UV-induced DNA damage. siRNA knockdown, Co-IP (MTA1-ATR), Western blot, gamma-H2AX focus assay, cell cycle analysis The Journal of biological chemistry High 20427275
2010 MTA1 is required for expression of MyD88 in LPS-stimulated macrophages and for MyD88-dependent NF-κB signaling. LPS stimulation promotes enhanced recruitment of MTA1, RNA Pol II, and p65RelA to NF-κB consensus sites in the MyD88 promoter. MTA1 depletion substantially reduces expression of NF-κB target genes (IL-1β, MIP2, TNF-α). ChIP, siRNA knockdown, NF-κB inhibitor (parthenolide) treatment, reporter assay, cytokine expression analysis The Journal of biological chemistry High 20702415
2010 MTA1 is an obligatory coregulator of transglutaminase 2 (TG2) expression in LPS-stimulated macrophages. MTA1 depletion impairs basal and LPS-induced TG2 expression. MTA1, p65RelA, and RNA Pol II are recruited to NF-κB consensus sites in the TG2 promoter during LPS stimulation. ChIP, siRNA knockdown, gene expression analysis, NF-κB inhibitor treatment The Journal of biological chemistry High 21156794
2011 MTA1 is SUMOylated by SUMO2/3 in vivo at Lys509 within a SUMO consensus site. PIAS proteins enhance SUMOylation of MTA1, while SENP1 and SENP2 act as deSUMOylation enzymes. MTA1 contains a functional SUMO-interacting motif (SIM) at its C terminus required for efficient SUMOylation. SUMO conjugation on Lys509 together with SIM synergistically regulates MTA1 co-repressor activity on pS2 transcription, likely by recruiting HDAC2 to the pS2 promoter. MTA1 also upregulates SUMO2 expression by interacting with RNA Pol II and SP1 at the SUMO2 promoter. In vivo SUMOylation assay, site-directed mutagenesis (K509), Co-IP, reporter assay, ChIP The Journal of biological chemistry High 21965678
2012 p53 mediates transcriptional repression of the MTA1 gene through two p53-response elements (p53REs) in the MTA1 promoter. This repression requires poly(ADP-ribosyl)ation of p53 by PARP-1 (identified in the repressor complex by proteomics). p53 and HDAC1/2 are recruited to the MTA1 promoter after 5-FU treatment, with decreased H3K9 acetylation. Repression occurs only in p53 wild-type cells. ChIP, reporter assay, siRNA, proteomics/pull-down of promoter-bound complex, PARP-1 inhibition Oncogene High 22286760
2012 MTA1 transcriptionally represses SMAD7 (an inhibitory SMAD and negative regulator of TGF-β signaling) in breast cancer cell lines. MTA1 is recruited to the SMAD7 promoter. MTA1 knockdown increases SMAD7 expression (reversed by HDAC inhibitor), and decreases levels of active SMAD2 and SMAD3. ChIP, shRNA knockdown, HDAC inhibitor treatment, Western blot European journal of cancer Medium 22841502
2013 MTA1 acts as a mandatory modifier of breast-to-lung metastasis (without affecting primary tumor formation) in a spontaneous mouse model. The mechanism involves MTA1-dependent stimulation of STAT3 transcription through formation of an MTA1/STAT3/Pol II coactivator complex, and consequent expression of STAT3 target genes including Twist1. Genetic depletion of MTA1 in spontaneous mouse breast cancer model, Co-IP (MTA1/STAT3/Pol II complex), gene expression analysis, ChIP Cancer research High 23580571
2014 Crystal structure of RbAp48-MTA1 subcomplex was determined. RbAp48 recognizes MTA1 using the same surface it uses to bind histone H4, showing that NuRD assembly modulates RbAp46/48 interactions with histones. The MTA proteins act as scaffolds for NuRD complex assembly, and the RbAp48-MTA1 interaction is essential for in vivo integration of RbAp46/48 into the NuRD complex. Crystal structure determination, in vitro binding assay, in vivo NuRD complex assembly assay The Journal of biological chemistry High 24920672
2014 MTA1 localizes to the nucleus, cytoplasm, and nuclear envelope. Nuclear envelope localization depends on TPR (translocated promoter region). Cytoplasmic MTA1 associates with microtubules. Nuclear but not cytoplasmic MTA1 is associated with cancer differentiation: MTA1 overexpression inhibits differentiation and promotes proliferation in HCT116 cells, while MTA1 knockdown results in cell differentiation and death. Multiple immunofluorescence/localization approaches, siRNA knockdown, OE, differentiation assays Oncotarget Medium 24970816
2014 MTA1 is a higher-order chromatin structure organizer that decondenses interphase chromatin and mitotic chromosomes. MTA1 interacts dynamically with nucleosomes during the cell cycle. MTA1-induced chromatin decondensation is independent of Mi-2 chromatin remodeling activity. MTA1 causes reduced histone H1-chromatin interaction in vivo, and this dynamic MTA1-chromatin interaction contributes to periodic H1-chromatin interaction modulating chromatin/chromosome transitions. Live-cell imaging, FRAP, chromatin fractionation, siRNA/OE experiments, chromosome structure analysis Molecular oncology Medium 25205035
2016 MTA1 can bind two molecules of RBBP4 (RbAp48). Negative stain electron microscopy and chemical crosslinking data provide a low-resolution model of an MTA1-(RBBP4)2 subcomplex within NuRD. In vitro binding/pull-down, negative stain EM, chemical crosslinking mass spectrometry Protein science High 27144666
2017 MTA1 directly induces miR-22 (Epi-miR) expression in prostate cancer cells. MiR-22 directly targets the 3'-UTR of E-cadherin, reducing its expression. MTA1 overexpression promotes invasiveness and migration via this MTA1/miR-22/E-cadherin axis. siRNA/OE loss- and gain-of-function, luciferase 3'-UTR reporter assay, ChIP for MTA1 at miR-22 locus FEBS letters Medium 28231399
2017 MTA1 promotes transcription of ErbB2 by binding with HDAC2 and acting at the ErbB2 promoter in hepatocellular carcinoma cells. The EMT-promoting effect caused by MTA1 largely depends on ErbB2; reducing ErbB2 activity attenuates MTA1-induced EMT both in vitro and in vivo. ChIP (MTA1 and HDAC2 at ErbB2 promoter), siRNA/OE, Co-IP, in vivo tumor model Oncogene Medium 28288133
2018 PWWP2A interacts with an MTA1-specific subcomplex of NuRD (M1HR) consisting solely of MTA1, HDAC1, and RBBP4/7 (excluding CHD, GATAD2, and MBD proteins). PWWP2A depletion leads to increased acetylation of H3K27 and H2A.Z, suggesting PWWP2A directs M1HR to H2A.Z-containing chromatin to promote deacetylation. Affinity purification/MS, Co-IP, ChIP-seq, siRNA knockdown with histone acetylation readout Nature communications High 30327463
2019 MTA1 regulates LDHA expression by interacting with c-Myc and recruiting the MTA1-c-Myc complex to the LDHA promoter. LDHA knockdown in MTA1-stably expressing MCF7 cells reduces cell migration, linking MTA1-LDHA axis to breast cancer motility. ChIP (MTA1 and c-Myc at LDHA promoter), Co-IP, siRNA, migration assay Biochemical and biophysical research communications Medium 31570164
2019 VEGF induces tyrosine phosphorylation of endogenous MTA1 mediated through VEGFR2 and p38-MAP kinase. Extracellular recombinant MTA1 protein binds to cell membranes (distinct from nuclear MTA1), activates ERK and JNK pathways, and induces angiogenesis comparable to or exceeding VEGF. MTA1 upregulates VEGF and Flt-1 gene expression via their promoters. Recombinant MTA1 protein treatment, immunofluorescence for cell membrane binding, phosphorylation assays, luciferase reporter (VEGF/Flt-1 promoters), in vivo angiogenesis models (cornea, CAM, xenograft) Molecular carcinogenesis Medium 24265228
2019 MTA1 is transferred between breast cancer cells via exosomes and can be delivered to vascular endothelial cells. Exosome-transferred MTA1 regulates hypoxic response (co-repressor function) and estrogen receptor signaling (co-activator function) in recipient cells. MTA1 knockout reduces cell proliferation and attenuates hypoxic response, rescued by addition of MTA1-containing exosomes. Antibody array, CRISPR/Cas9 MTA1 knockout, tdTomato-MTA1 ectopic expression and exosome tracking by fluorescence microscopy, reporter assays, exosome transfer experiments Cell communication and signaling Medium 30782165
2019 TGF-β induces MTA1 expression, and MTA1 acts upstream of SOX4 in the TGF-β pathway. The TGF-β-MTA1-SOX4-EZH2 signaling axis drives EMT in multiple cancer cell lines. MTA1 overexpression activates SOX4, which in turn activates EZH2; epistasis experiments show MTA1 is upstream of SOX4 and that SOX4 is required for MTA1-driven EMT. Epistasis/pathway dissection by siRNA and OE, gene expression profiling, shRNA, in vitro EMT assays in multiple cell lines, TCGA analysis Oncogene Medium 31811272
2020 MTA1 broadly interacts with RNA-binding proteins (RBPs) and directly binds abundant transcripts (preferentially at splicing-responsible motifs) as shown by fCLIP-seq. MTA1 regulates mRNA levels and alternative splicing of mitosis regulators including ATRX and MYBL2. MTA1 deletion causes defective mitotic arrest, aberrant chromosome segregation, and chromosomal instability (CIN), contributing to tumorigenesis. fCLIP-seq, RNA-seq, siRNA/KO, chromosome segregation and CIN assays, alternative splicing analysis Nature communications High 32901005
2021 O-GlcNAc modification of MTA1 at serine residues S237/S241/S246 (identified by quantitative proteomics) promotes MTA1 interaction with chromatin and enhances its association with the NuRD complex. O-GlcNAc-modified MTA1 shows altered genome-wide chromatin binding patterns (ChIP-seq) and changes expression of target genes involved in genotoxic adaptation in adriamycin-resistant breast cancer cells. Quantitative proteomics (mass spectrometry of O-GlcNAc sites), ChIP-seq, transcriptome analysis, OGT inhibition/OE Biochimica et biophysica acta. General subjects Medium 34019948
2022 RUNX2 recruits the MTA1/NuRD complex and the CUL4B-Ring E3 ligase (CRL4B) complex to form a transcriptional-repressive complex that catalyzes both histone deacetylation and ubiquitylation. Genome-wide analysis identified PPARα and SOD2 as targets of the RUNX2/NuRD(MTA1)/CRL4B complex. This complex promotes breast cancer proliferation, invasion, bone metastasis, and cancer stemness. Co-IP, ChIP-seq, genome-wide target analysis, in vitro and in vivo functional assays (proliferation, invasion, bone metastasis xenograft) Cell death and differentiation High 35534547
2022 RNA-binding protein RALY cooperates with splicing factor SF3B3 to regulate MTA1 alternative splicing, switching from the MTA1-S isoform to MTA1-L. MTA1-S (short isoform) normally inhibits cell proliferation by reducing transcription of cholesterol synthesis genes; the RALY/SF3B3-driven splicing switch reduces MTA1-S levels and thereby relieves inhibition of cholesterol synthesis, promoting hepatocellular carcinoma proliferation. RNA splicing assays, siRNA/OE of RALY and SF3B3, gene expression analysis, cholesterol synthesis pathway analysis, cell proliferation assays Cancer letters Medium 35490918
2001 Nuclear localization of mouse Mta1 depends on the presence of at least one nuclear localization signal (NLS) and one SH3 binding site (proline-rich Src homology 3 ligand) in the C-terminal region. These SH3 ligands facilitate interaction with the adaptor protein Grb2 and the Src-family tyrosine kinase Fyn. GFP-Mta1 localizes exclusively in the nucleus while GFP-Mta3 is present in both nucleus and cytoplasm. GFP-tagged deletion construct expression, fluorescence microscopy, Co-IP (Grb2/Fyn interaction) Gene Medium 11483358
2010 MTA1 induces AMPK activation (associated with increased AMP:ATP ratio and decreased mitochondrial electron transport complex components) and subsequent autophagy flux, contributing to tamoxifen resistance in breast cancer cells. ATG7 knockdown or autophagy inhibition (hydroxychloroquine) restores tamoxifen sensitivity in MTA1-overexpressing and tamoxifen-resistant cells. Stable MTA1 overexpression cell line, siRNA (ATG7), autophagy flux assay, in vitro and in vivo growth assays, AMPK activation assays Autophagy Medium 29130361

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2002 A naturally occurring MTA1 variant sequesters oestrogen receptor-alpha in the cytoplasm. Nature 198 12167865
2012 Leptin-induced epithelial-mesenchymal transition in breast cancer cells requires β-catenin activation via Akt/GSK3- and MTA1/Wnt1 protein-dependent pathways. The Journal of biological chemistry 165 22270359
1997 Overexpression of the MTA1 gene in gastrointestinal carcinomas: correlation with invasion and metastasis. International journal of cancer 151 9291440
2008 Hepatitis B virus X protein induces the expression of MTA1 and HDAC1, which enhances hypoxia signaling in hepatocellular carcinoma cells. Oncogene 143 18264140
2010 Resveratrol enhances p53 acetylation and apoptosis in prostate cancer by inhibiting MTA1/NuRD complex. International journal of cancer 130 19810103
2003 Tumor metastasis-associated human MTA1 gene and its MTA1 protein product: role in epithelial cancer cell invasion, proliferation and nuclear regulation. Clinical & experimental metastasis 130 12650603
2012 Akt mediates metastasis-associated gene 1 (MTA1) regulating the expression of E-cadherin and promoting the invasiveness of prostate cancer cells. PloS one 122 23227138
1999 Overexpression of metastasis-associated MTA1 mRNA in invasive oesophageal carcinomas. British journal of cancer 103 10206283
2014 Resveratrol regulates PTEN/Akt pathway through inhibition of MTA1/HDAC unit of the NuRD complex in prostate cancer. Biochimica et biophysica acta 100 25447541
2006 MTA1, a transcriptional activator of breast cancer amplified sequence 3. Proceedings of the National Academy of Sciences of the United States of America 99 16617102
2004 Expression of the metastasis-associated MTA1 protein and its relationship to deacetylation of the histone H4 in esophageal squamous cell carcinomas. International journal of cancer 91 15095300
2006 MTA1 overexpression correlates significantly with tumor grade and angiogenesis in human breast cancers. Cancer science 83 16630134
2002 Metastasis-associated protein (MTA)1 enhances migration, invasion, and anchorage-independent survival of immortalized human keratinocytes. Oncogene 82 11948399
2016 MicroRNA-543 suppresses colorectal cancer growth and metastasis by targeting KRAS, MTA1 and HMGA2. Oncotarget 81 26968810
2019 A TGF-β-MTA1-SOX4-EZH2 signaling axis drives epithelial-mesenchymal transition in tumor metastasis. Oncogene 78 31811272
2014 Role of MTA1 in cancer progression and metastasis. Cancer metastasis reviews 76 25344802
2002 Expression of the MTA1 mRNA in advanced lung cancer. Lung cancer (Amsterdam, Netherlands) 75 11804687
2018 MTA1 is a novel regulator of autophagy that induces tamoxifen resistance in breast cancer cells. Autophagy 73 29130361
2009 E3 ubiquitin ligase COP1 regulates the stability and functions of MTA1. Proceedings of the National Academy of Sciences of the United States of America 73 19805145
2014 Insight into the architecture of the NuRD complex: structure of the RbAp48-MTA1 subcomplex. The Journal of biological chemistry 69 24920672
2022 RUNX2 recruits the NuRD(MTA1)/CRL4B complex to promote breast cancer progression and bone metastasis. Cell death and differentiation 65 35534547
2008 The metastasis-associated gene MTA1 is upregulated in advanced ovarian cancer, represses ERbeta, and enhances expression of oncogenic cytokine GRO. Cancer biology & therapy 65 18719363
2007 MTA1-mediated transcriptional repression of BRCA1 tumor suppressor gene. Oncogene 63 17922032
2014 Curcumin suppresses proliferation and invasion in non-small cell lung cancer by modulation of MTA1-mediated Wnt/β-catenin pathway. In vitro cellular & developmental biology. Animal 60 24938356
2007 Identification of Pax5 as a target of MTA1 in B-cell lymphomas. Cancer research 60 17671180
2002 Repression of 92-kDa type IV collagenase expression by MTA1 is mediated through direct interactions with the promoter via a mechanism, which is both dependent on and independent of histone deacetylation. The Journal of biological chemistry 60 12431981
2019 Metastasis-associated protein 1 (MTA1) is transferred by exosomes and contributes to the regulation of hypoxia and estrogen signaling in breast cancer cells. Cell communication and signaling : CCS 57 30782165
2013 MTA1 promotes STAT3 transcription and pulmonary metastasis in breast cancer. Cancer research 56 23580571
2004 Expression of MTA1 promotes motility and invasiveness of PANC-1 pancreatic carcinoma cells. British journal of cancer 54 14735193
2019 Hsa_circ_0039411 promotes tumorigenesis and progression of papillary thyroid cancer by miR-1179/ABCA9 and miR-1205/MTA1 signaling pathways. Journal of cellular physiology 52 31270819
2016 Dietary pterostilbene is a novel MTA1-targeted chemopreventive and therapeutic agent in prostate cancer. Oncotarget 52 26943043
2003 MICoA, a novel metastasis-associated protein 1 (MTA1) interacting protein coactivator, regulates estrogen receptor-alpha transactivation functions. The Journal of biological chemistry 52 12639951
2022 MTA1-mediated RNA m6 A modification regulates autophagy and is required for infection of the rice blast fungus. The New phytologist 49 35338654
2003 MTA1 interacts with MAT1, a cyclin-dependent kinase-activating kinase complex ring finger factor, and regulates estrogen receptor transactivation functions. The Journal of biological chemistry 49 12527756
2010 Revelation of p53-independent function of MTA1 in DNA damage response via modulation of the p21 WAF1-proliferating cell nuclear antigen pathway. The Journal of biological chemistry 48 20071335
2013 MTA1 promotes the invasion and migration of non-small cell lung cancer cells by downregulating miR-125b. Journal of experimental & clinical cancer research : CR 46 23718732
2018 PWWP2A binds distinct chromatin moieties and interacts with an MTA1-specific core NuRD complex. Nature communications 45 30327463
2009 MTA1 coregulator regulates p53 stability and function. The Journal of biological chemistry 45 19837670
2006 Reduced MTA1 expression by RNAi inhibits in vitro invasion and migration of esophageal squamous cell carcinoma cell line. Clinical & experimental metastasis 45 16703414
2006 Expression of metastasis-associated protein 1 (MTA1) in benign endometrium and endometrial adenocarcinomas. Human pathology 45 16733204
2000 Expression of MTA1, a metastasis-associated gene with histone deacetylase activity in pancreatic cancer. International journal of oncology 45 10811997
2013 MTA-1 expression is associated with metastasis and epithelial to mesenchymal transition in colorectal cancer cells. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 44 23371285
2007 Small bowel carcinoid (enterochromaffin cell) neoplasia exhibits transforming growth factor-beta1-mediated regulatory abnormalities including up-regulation of C-Myc and MTA1. Cancer 43 17469181
2014 Towards an understanding of the structure and function of MTA1. Cancer metastasis reviews 42 25352341
2009 The metastasis-associated genes MTA1 and MTA3 are abundantly expressed in human placenta and chorionic carcinoma cells. Histochemistry and cell biology 42 19363681
2017 Targeting MTA1/HIF-1α signaling by pterostilbene in combination with histone deacetylase inhibitor attenuates prostate cancer progression. Cancer medicine 40 29024573
2017 MTA1-activated Epi-microRNA-22 regulates E-cadherin and prostate cancer invasiveness. FEBS letters 39 28231399
2012 Poly(ADP-ribosyl)ation of p53 induces gene-specific transcriptional repression of MTA1. Oncogene 39 22286760
2001 Differential expression and subcellular distribution of the mouse metastasis-associated proteins Mta1 and Mta3. Gene 39 11483358
2018 Pterostilbene inhibits MTA1/HDAC1 complex leading to PTEN acetylation in hepatocellular carcinoma. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 38 29635894
2015 miR-125a-3p targets MTA1 to suppress NSCLC cell proliferation, migration, and invasion. Acta biochimica et biophysica Sinica 38 25998575
2017 Andrographolide reduced VEGFA expression in hepatoma cancer cells by inactivating HIF-1α: The involvement of JNK and MTA1/HDCA. Chemico-biological interactions 37 28651835
2010 MTA1 coregulation of transglutaminase 2 expression and function during inflammatory response. The Journal of biological chemistry 36 21156794
1999 Molecular cloning, mapping, and characterization of a novel human gene, MTA1-L1, showing homology to a metastasis-associated gene, MTA1. Journal of human genetics 36 9929979
2008 Overexpression of metastasis-associated MTA1 in oral squamous cell carcinomas: correlation with metastasis and invasion. International journal of oral and maxillofacial surgery 35 18640824
2019 Interleukin-17 Promotes Migration and Invasion of Human Cancer Cells Through Upregulation of MTA1 Expression. Frontiers in oncology 34 31281798
2017 Curcumin increases the sensitivity of Paclitaxel-resistant NSCLC cells to Paclitaxel through microRNA-30c-mediated MTA1 reduction. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 34 28443468
2015 Inhibition of MTA1 by ERα contributes to protection hepatocellular carcinoma from tumor proliferation and metastasis. Journal of experimental & clinical cancer research : CR 34 26503703
2010 Requirement of MTA1 in ATR-mediated DNA damage checkpoint function. The Journal of biological chemistry 34 20427275
2018 MicroRNA-183 Acts as a Tumor Suppressor in Human Non-Small Cell Lung Cancer by Down-Regulating MTA1. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 33 29587281
2017 MTA1 modulated by miR-30e contributes to epithelial-to-mesenchymal transition in hepatocellular carcinoma through an ErbB2-dependent pathway. Oncogene 33 28288133
2014 The subcellular distribution and function of MTA1 in cancer differentiation. Oncotarget 33 24970816
2001 Expression of the MTA1 mRNA in thymoma patients. Cancer letters 33 11689291
2011 Gene profiling of MTA1 identifies novel gene targets and functions. PloS one 31 21364872
2016 Crosstalk between ATF4 and MTA1/HDAC1 promotes osteosarcoma progression. Oncotarget 30 26797758
2010 MTA1 coregulator regulates LPS response via MyD88-dependent signaling. The Journal of biological chemistry 30 20702415
2022 RNA binding protein RALY activates the cholesterol synthesis pathway through an MTA1 splicing switch in hepatocellular carcinoma. Cancer letters 29 35490918
2018 FMNL1 mediates nasopharyngeal carcinoma cell aggressiveness by epigenetically upregulating MTA1. Oncogene 28 30013189
2017 MTA1 expression in human cancers - Clinical and pharmacological significance. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 28 28915537
2016 The MTA1 subunit of the nucleosome remodeling and deacetylase complex can recruit two copies of RBBP4/7. Protein science : a publication of the Protein Society 28 27144666
2020 Chromatin modifier MTA1 regulates mitotic transition and tumorigenesis by orchestrating mitotic mRNA processing. Nature communications 27 32901005
2011 SUMOylation and SUMO-interacting motif (SIM) of metastasis tumor antigen 1 (MTA1) synergistically regulate its transcriptional repressor function. The Journal of biological chemistry 27 21965678
2018 MTA1 drives malignant progression and bone metastasis in prostate cancer. Molecular oncology 26 30027683
2012 MTA1-mediated transcriptional repression of SMAD7 in breast cancer cell lines. European journal of cancer (Oxford, England : 1990) 26 22841502
2014 Properties and clinical relevance of MTA1 protein in human cancer. Cancer metastasis reviews 25 25359582
2016 Effects of Per2 overexpression on growth inhibition and metastasis, and on MTA1, nm23-H1 and the autophagy-associated PI3K/PKB signaling pathway in nude mice xenograft models of ovarian cancer. Molecular medicine reports 24 27082164
2013 Crosstalk between VEGF and MTA1 signaling pathways contribute to aggressiveness of breast carcinoma. Molecular carcinogenesis 24 24265228
2018 MiR-421 inhibited proliferation and metastasis of colorectal cancer by targeting MTA1. Journal of B.U.ON. : official journal of the Balkan Union of Oncology 23 30610787
2017 MTA1 promotes epithelial to mesenchymal transition and metastasis in non-small-cell lung cancer. Oncotarget 23 28418915
2021 FOXP3 Inhibits the Metastasis of Breast Cancer by Downregulating the Expression of MTA1. Frontiers in oncology 22 34307133
2021 Ellagic Acid Alleviates Rheumatoid Arthritis in Rats through Inhibiting MTA1/HDAC1-Mediated Nur77 Deacetylation. Mediators of inflammation 22 34924813
2012 β-elemene acts as an antitumor factor and downregulates the expression of survivin, Bcl-xL and Mta-1. Molecular medicine reports 22 22895653
2020 MTA1, a Target of Resveratrol, Promotes Epithelial-Mesenchymal Transition of Endometriosis via ZEB2. Molecular therapy. Methods & clinical development 21 33145366
2019 Correlation of two distinct metastasis-associated proteins, MTA1 and S100A4, in angiogenesis for promoting tumor growth. Oncogene 21 30745574
2015 YB-1 and MTA1 protein levels and not DNA or mRNA alterations predict for prostate cancer recurrence. Oncotarget 21 25797255
2021 O-GlcNAc modification regulates MTA1 transcriptional activity during breast cancer cell genotoxic adaptation. Biochimica et biophysica acta. General subjects 19 34019948
2019 MTA1 coregulator regulates LDHA expression and function in breast cancer. Biochemical and biophysical research communications 19 31570164
2015 Hypoxia-induced MTA1 promotes MC3T3 osteoblast growth but suppresses MC3T3 osteoblast differentiation. European journal of medical research 19 25644400
2013 MTA1 promotes nasopharyngeal carcinoma growth in vitro and in vivo. Journal of experimental & clinical cancer research : CR 19 23941622
2021 TGF-β-MTA1-SMAD7-SMAD3-SOX4-EZH2 Signaling Axis Promotes Viability, Migration, Invasion and EMT of Hepatocellular Carcinoma Cells. Cancer management and research 18 34531686
2014 MTA1 regulates higher-order chromatin structure and histone H1-chromatin interaction in-vivo. Molecular oncology 18 25205035
2011 MTA1 expression correlates significantly with cigarette smoke in non-small cell lung cancer. Virchows Archiv : an international journal of pathology 18 21892752
2019 MTA1-Dependent Anticancer Activity of Gnetin C in Prostate Cancer. Nutrients 17 31487842
2018 MTA1 promotes the invasion and migration of pancreatic cancer cells potentially through the HIF-α/VEGF pathway. Journal of receptor and signal transduction research 17 30396299
2015 MTA1 promotes metastasis of MPM via suppression of E-cadherin. Journal of experimental & clinical cancer research : CR 17 26689197
2009 Immunohistochemical and clinicopathological correlation of the metastasis-associated gene 1 (MTA1) expression in benign and malignant pancreatic endocrine tumors. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 17 19377441
2019 MTA1 promotes the invasion and migration of oral squamous carcinoma by inducing epithelial-mesenchymal transition via the hedgehog signaling pathway. Experimental cell research 16 31152708
2015 MTA1 promotes proliferation and invasion in human gastric cancer cells. OncoTargets and therapy 16 26229486
2013 MTA1 contributes to actin cytoskeleton reorganization and metastasis of nasopharyngeal carcinoma by modulating Rho GTPases and Hedgehog signaling. The international journal of biochemistry & cell biology 16 23618874
2014 Function and regulation of MTA1 and MTA3 in malignancies of the female reproductive system. Cancer metastasis reviews 15 25319202

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