Affinage

MED23

Mediator of RNA polymerase II transcription subunit 23 · UniProt Q9ULK4

Length
1368 aa
Mass
156.5 kDa
Annotated
2026-06-10
42 papers in source corpus 27 papers cited in narrative 26 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

MED23 is a tail-module subunit of the Mediator complex that functions as a signal-specific transcriptional coactivator, transducing inputs from sequence-specific transcription factors to RNA polymerase II to govern lineage-specific gene programs (PMID:15297616, PMID:19460352). Its defining feature is selectivity: distinct activators engage MED23 to drive context-dependent outputs, exemplified by insulin/MAPK signaling channeled through ELK1 to induce the immediate-early gene Krox20 during adipogenesis, where Med23-null cells fail to assemble a functional preinitiation complex at the Krox20 promoter (PMID:19460352). MED23 frequently acts as a molecular switch by dictating which partner occupies a shared transcription factor: at SRF-bound promoters MED23 favors ELK1-SRF over MAL/MRTF-SRF binding, thereby toggling cell-fate decisions between smooth muscle/myogenic differentiation and proliferation (PMID:22972934, PMID:38691453). Beyond preinitiation, MED23 promotes transcription elongation by directly binding the CDK9 subunit of P-TEFb to deposit phospho-Ser2 RNAP II across coding regions (PMID:23340209), and it couples transcription to chromatin by recruiting the RNF20/40 E3 ligase complex—together with the PAF complex—to catalyze H2B K120 monoubiquitination on active genes (PMID:26330467). MED23 also shapes enhancer chromatin states by modulating P300-directed H3K27 acetylation at Sp1 target genes during oligodendrocyte differentiation (PMID:39402028) and by facilitating G9a-mediated H3K9 dimethylation at repressed chemokine promoters via the nuclear receptor RORα (PMID:31805036). Through these mechanisms MED23 directs adipocyte, smooth muscle, osteoblast, oligodendrocyte, muscle stem cell, and hematopoietic lineage decisions (PMID:19460352, PMID:27033977, PMID:30218073, PMID:39402028, PMID:38691453), controls hepatic glucose and lipid metabolism through FOXO1 (PMID:25223702), regulates innate antiviral immunity through IRF7-IFNλ and FOXO3-RIG-I axes (PMID:23950709, PMID:40705824), and modulates Ras-driven proliferation and tumorigenesis (PMID:22988093, PMID:35963541, PMID:41436431). A patient-derived Med23 variant (Q649R) modeled in a knock-in mouse links MED23 to an oligodendrocyte/myelination phenotype (PMID:39402028).

Mechanistic history

Synthesis pass · year-by-year structured walk · 25 steps
  1. 2003 Medium

    Established MED23 (CRSP3) as a transcriptional coactivator with tumor-suppressive output, linking it to metastasis suppressor gene expression before its Mediator mechanism was dissected.

    Evidence Subtractive hybridization, transfection/overexpression and expression correlation across melanoma lines

    PMID:12543799

    Open questions at the time
    • No direct physical interaction between MED23 and KISS1/TXNIP regulatory machinery shown
    • Mechanism of coactivation not resolved at this stage
  2. 2004 Medium

    Showed that individual Mediator subunits, including MED23, are required for signal-specific transcriptional activation rather than general transcription, defining the principle of activator-selective Mediator function.

    Evidence RNAi depletion of individual Mediator subunits with promoter activation assays in Drosophila

    PMID:15297616

    Open questions at the time
    • Direct activator–MED23 contacts not biochemically mapped
    • Mammalian generality untested at this point
  3. 2009 High

    Defined the first molecular pathway for MED23 by showing it links insulin/MAPK signaling to adipogenesis via ELK1-driven Krox20 induction and preinitiation complex assembly.

    Evidence Med23 knockout MEFs, dominant-negative ELK1, and epistasis rescue with Krox20/C/EBPβ/PPARγ

    PMID:19460352

    Open questions at the time
    • Structural basis of MED23–ELK1 contact not defined
    • Whether the same module operates in other lineages untested here
  4. 2012 High

    Extended MED23 function beyond promoter activation by demonstrating direct interaction with hnRNP L to regulate alternative splicing and polyadenylation, coupling Mediator to co-transcriptional mRNA processing.

    Evidence TAP-MS, reciprocal Co-IP, ChIP-seq, and minigene reporters

    PMID:22264826

    Open questions at the time
    • Direct binding interface between MED23 and hnRNP L not mapped
    • Scope of processing events controlled genome-wide only partially defined
  5. 2012 High

    Revealed MED23 as a binary cell-fate switch that controls SRF cofactor choice (ELK1-SRF vs MAL-SRF), explaining how it directs smooth muscle versus adipocyte differentiation.

    Evidence Med23 knockout cells, ChIP of differential SRF partner binding, zebrafish in vivo validation

    PMID:22972934

    Open questions at the time
    • Mechanism by which MED23 biases SRF partner selection not structurally resolved
  6. 2012 High

    Connected MED23 to oncogenic Ras dependency by showing it co-regulates ELK1-driven proliferation genes selectively required for Ras-active tumor cells.

    Evidence RNAi screen across lung cancer lines, Ras vs Myc transformation epistasis, transcriptome analysis

    PMID:22988093

    Open questions at the time
    • Therapeutic targetability not addressed at this stage
    • Direct ELK1–MED23 contact in this context not biochemically isolated
  7. 2013 High

    Demonstrated a previously unrecognized role for MED23 in transcription elongation through direct CDK9/P-TEFb recruitment, separating its elongation function from preinitiation.

    Evidence In vitro and in vivo MED23–CDK9 Co-IP, ChIP-seq for P-TEFb and Ser2-phospho RNAP II in Med23-null ES cells

    PMID:23340209

    Open questions at the time
    • Domain of MED23 binding CDK9 not mapped
    • Relationship to activator-specific recruitment not defined
  8. 2013 Medium

    Identified MED23 as an antiviral effector that drives IFN-λ via IRF7, linking Mediator to innate immune transcription.

    Evidence Yeast two-hybrid MED23–IRF7, RNAi and overexpression, IFN-λ quantification with virus specificity controls

    PMID:23950709

    Open questions at the time
    • IRF7 interaction not confirmed by orthogonal biochemistry beyond Y2H
    • Why effect is HSV-1-specific unexplained
  9. 2014 High

    Showed MED23 controls hepatic energy homeostasis by facilitating Mediator/RNAPII recruitment to FOXO1 target genes, an evolutionarily conserved metabolic axis.

    Evidence Liver-specific Med23 KO and acute knockdown in db/db mice, ChIP, Drosophila genetic epistasis

    PMID:25223702

    Open questions at the time
    • Direct MED23–FOXO1 binding interface not mapped
    • Contribution of elongation vs initiation steps to this output undefined
  10. 2014 Medium

    Established MED23 as a restraint on T-cell activation operating through MEF2-driven KLF2 expression, defining an immune lineage role.

    Evidence Conditional Lck-Cre Med23 KO, expression profiling, MEF2 activity assays in MED23-null MEFs

    PMID:25054639 PMID:25301163

    Open questions at the time
    • Direct MED23–MEF2 physical interaction not demonstrated
    • Mechanism linking MED23 loss to negative-regulator gene repression incomplete
  11. 2015 High

    Demonstrated that MED23 couples transcription to chromatin by recruiting RNF20/40 to deposit H2B monoubiquitination, providing a reconstituted biochemical mechanism.

    Evidence TAP-MS, cell-free reconstitution on recombinant chromatin with RNF20/40 and PAF, genome-wide H2Bub ChIP-seq

    PMID:26330467

    Open questions at the time
    • Determinants selecting which genes receive MED23-dependent H2Bub unclear
    • Interplay with elongation machinery not fully integrated
  12. 2015 Medium

    Showed MED23 restrains neural differentiation of ESCs by sustaining BMP signaling through ETS1-directed Bmp4 expression.

    Evidence Med23 knockdown ESCs, ChIP, minigene reporter, zebrafish morpholino rescue with bmp4 mRNA

    PMID:25564654

    Open questions at the time
    • Direct MED23–ETS1 binding not biochemically isolated
  13. 2016 High

    Defined MED23 as a physical and genetic partner of RUNX2 controlling osteoblast differentiation without altering RUNX2 levels.

    Evidence Conditional KO, Co-IP of MED23–RUNX2, Med23/Runx2 compound mutant epistasis

    PMID:27033977

    Open questions at the time
    • Interaction interface unmapped
    • Whether RUNX2 output uses elongation or chromatin arms of MED23 untested
  14. 2017 Medium

    Linked MED23 to pigmentation and DNA repair via MITF enhancer control, broadening its developmental and genome-maintenance reach.

    Evidence Melanocyte conditional KO, zebrafish knockdown, NER assays, ChIP at Mitf enhancer

    PMID:28834744

    Open questions at the time
    • Whether MED23 acts directly at NER factor genes or solely through MITF unresolved
  15. 2017 Medium

    Showed conserved integration of EGFR and Notch signaling by SUR-2/MED23 with LIN-1/ELK1 in cell-fate patterning, independent of the Cdk8 kinase module.

    Evidence C. elegans genetics, cell-fate reporters, LIN-12-GFP endocytosis assay

    PMID:28954762

    Open questions at the time
    • Molecular basis for CKM-independence not defined
    • Mammalian counterpart of this Notch crosstalk untested
  16. 2018 Medium

    Identified MED23 as a gatekeeper of HSC myeloid potential and self-renewal through maintenance of stemness gene expression.

    Evidence Hematopoietic-specific Med23 KO, FACS, expression profiling

    PMID:30218073

    Open questions at the time
    • Transcription factor partner driving stemness program not identified
    • Direct target genes not biochemically mapped
  17. 2019 Medium

    Revealed a repressive chromatin mechanism for MED23 in which it cooperates with RORα and G9a to deposit H3K9me2 at chemokine promoters, limiting liver fibrosis.

    Evidence Liver-specific KO in CCl4 model, H3K9me2 ChIP, reporter assays

    PMID:31805036

    Open questions at the time
    • Direct MED23–RORα and MED23–G9a contacts not biochemically dissected
  18. 2020 Medium

    Positioned MED23 as a repressor of Sox9 and negative regulator of WNT signaling in neural crest, explaining craniofacial defects upon its loss.

    Evidence Wnt1-Cre conditional KO, ChIP at Sox9 promoter, repression reporter, Sox9–β-catenin Co-IP

    PMID:33155500 PMID:33192541

    Open questions at the time
    • Mechanism by which MED23 represses (vs activates) the Sox9 promoter unresolved
    • Transcription factor mediating MED23 occupancy at Sox9 not defined
  19. 2022 Medium

    Established MED23 as a regulator of vascular integrity by negatively controlling angiopoietin2, with cell-autonomous endothelial requirement.

    Evidence Endothelial-specific KO, HUVEC knockdown, RNA-seq, Ang2 inhibition rescue

    PMID:35440711

    Open questions at the time
    • Transcription factor partner directing Ang2 repression unidentified
  20. 2022 High

    Mapped the MED23–ELF3 interaction at residue resolution and showed pharmacological disruption attenuates HER2 oncogenic signaling, providing a druggable interface.

    Evidence Fluorescence polarization, GST pulldown, residue mutagenesis, SEAP reporter, xenograft with small molecule YK1

    PMID:35963541

    Open questions at the time
    • Crystal structure of the complex not solved
    • Selectivity of YK1 across other MED23 interactions not fully characterized
  21. 2024 High

    Showed MED23 drives oligodendrocyte differentiation and myelination by modulating P300-dependent H3K27 acetylation at Sp1 target genes, and linked a patient variant to this program via a knock-in model.

    Evidence Med23Q649R knock-in mouse, lineage-specific KO, ChIP for P300 and H3K27ac, reporter assays

    PMID:39402028

    Open questions at the time
    • How the Q649R variant alters specific molecular contacts not resolved
    • Direct MED23–Sp1 vs MED23–P300 contact contributions not separated
  22. 2024 Medium

    Identified a MED23/BCLAF1 complex regulating NUPR1 and autophagic flux, linking MED23 loss to premature senescence in NSCLC.

    Evidence Co-IP/MS, PLA, RNA-seq, ChIP

    PMID:39366174

    Open questions at the time
    • Direct vs indirect nature of NUPR1 regulation not fully separated
    • Interaction interface with BCLAF1 unmapped
  23. 2025 High

    Defined opposing MED23 control of SRF cofactor usage (TCF/ELK1-SRF vs MRTF-A/SRF) governing muscle stem cell proliferation versus differentiation during regeneration.

    Evidence MuSC-specific KO, injury model, myofiber culture, ChIP of ELK1/SRF and MRTF-A/SRF, integrative genomics

    PMID:38691453

    Open questions at the time
    • Structural basis of partner switching shared with smooth muscle context not resolved
  24. 2025 Medium

    Extended MED23 innate immune function to a FOXO3–RIG-I axis restraining antiviral interferon responses in myeloid cells.

    Evidence Myeloid-specific KO, MED23–FOXO3 Co-IP, viral challenge, cytokine/ISG quantification

    PMID:40705824

    Open questions at the time
    • MED23–FOXO3 binding interface unmapped
    • Relationship to earlier IRF7-IFNλ antiviral role not integrated
  25. 2025 Medium

    Showed MED23 promotes hepatocellular carcinoma through an RFX5-directed IGF2 enhancer and NQO1-dependent redox control, marking a tumor-promoting role in liver.

    Evidence Liver-specific KO in DEN-HCC model, ChIP at IGF2 enhancer, NQO1 stability and ROS assays, IGF2 rescue

    PMID:41436431

    Open questions at the time
    • Mechanism by which MED23 stabilizes NQO1 protein not defined
    • How a tumor-promoting hepatic role reconciles with tumor-suppressive roles elsewhere unresolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unresolved how MED23 selects among its many transcription factor partners in a given cell type and how its initiation, elongation, and chromatin-modifying activities are coordinated at individual loci.
  • No structural model of MED23 within the Mediator tail engaging activators
  • Rules governing activation vs repression outputs not defined
  • Reconciliation of context-dependent tumor-suppressor vs tumor-promoter roles lacking

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 4 GO:0098772 molecular function regulator activity 4 GO:0140110 transcription regulator activity 4
Localization
GO:0005634 nucleus 3 GO:0005654 nucleoplasm 3
Pathway
R-HSA-1266738 Developmental Biology 5 R-HSA-162582 Signal Transduction 4 R-HSA-1643685 Disease 3 R-HSA-4839726 Chromatin organization 3 R-HSA-74160 Gene expression (Transcription) 3 R-HSA-168256 Immune System 2 R-HSA-8953854 Metabolism of RNA 1
Partners
BCLAF1CDK9ELF3ELK1FOXO3HNRNPLIRF7RUNX2
Complex memberships
Mediator complex

Evidence

Reading pass · 26 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2003 CRSP3/MED23 (chromosome 6) acts as a transcriptional coactivator that functions upstream of TXNIP and KISS1 to suppress melanoma metastasis; CRSP3 transfection upregulates KISS1 and TXNIP expression, and loss of CRSP3 expression correlates with decreased KISS1 and increased metastasis in clinical samples. Subtractive hybridization, microarray, transfection/overexpression, quantitative RT-PCR Cancer research Medium 12543799
2004 In Drosophila, MED23 is specifically required for heat-shock-induced transcriptional activation and interacts with heat-shock-specific activators; MED16 is required for LPS-induced activation, demonstrating that distinct Mediator subunits interact with specific activators for signal-specific transcription. RNA interference depletion of individual Mediator subunits, endogenous and synthetic promoter activation assays, microarray Proceedings of the National Academy of Sciences of the United States of America Medium 15297616
2009 MED23 subunit of the Mediator Complex links insulin/MAPK signaling to adipogenesis by interacting with transcription factor ELK1 to drive expression of Krox20, an immediate early gene required for the adipogenic cascade; Med23-null cells fail to recruit a functional preinitiation complex at the Krox20 promoter upon insulin stimulation, and the adipogenic defect is rescued by ectopic Krox20, C/EBPβ, or PPARγ. Med23 knockout MEFs, knockdown/overexpression, dominant-negative ELK1, rescue experiments, preinitiation complex assay Developmental cell High 19460352
2012 MED23 regulates alternative mRNA processing by physically interacting with the splicing/polyadenylation factor hnRNP L (identified by tandem affinity purification/mass spectrometry and confirmed by in vitro and in vivo interaction assays); MED23 modulates a subset of hnRNP L-targeted alternative splicing and alternative cleavage and polyadenylation events, and ChIP-seq showed MED23 regulates hnRNP L occupancy at co-regulated genes. Tandem affinity purification, mass spectrometry, co-IP (in vitro and in vivo), minigene reporters, exon array, ChIP-seq Molecular cell High 22264826
2012 MED23 controls a binary cell fate decision between smooth muscle cells (SMCs) and adipocytes from mesenchymal stem cells: Med23 deficiency facilitates SMC differentiation and represses adipocyte differentiation. Mechanistically, MED23 favors ELK1-SRF binding at SMC gene promoters for repression, while absence of MED23 favors MAL-SRF binding at the same promoters for activation of cytoskeletal/SMC genes. Med23 knockout cells, gene profiling, ChIP, overexpression, zebrafish embryo injection Genes & development High 22972934
2012 MED23 is selectively required for the proliferation and tumorigenicity of Ras-active lung cancer cells; MED23 co-regulates with ELK1 (phosphorylated by MAPK downstream of Ras) a set of cell-cycle/proliferation genes supporting Ras addiction; Med23 deficiency in fibroblasts selectively blocked oncogenic Ras- but not c-Myc-induced transformation. RNAi screen across lung cancer cell lines, Med23 knockdown, transcriptome analysis, transformation assays Proceedings of the National Academy of Sciences of the United States of America High 22988093
2013 MED23 regulates basal transcription elongation by recruiting the elongation factor P-TEFb through a direct physical interaction with its CDK9 subunit; Med23 deficiency reduces P-TEFb and phospho-Ser2 RNAP II occupancy at the coding region of target genes without altering RNAP II, GTFs, or Mediator occupancy at the promoter, and does not affect DSIF or NELF occupancy. Co-IP in vivo and in vitro (MED23-CDK9), ChIP, ChIP-seq, qRT-PCR in Med23-null ES cells Transcription High 23340209
2013 MED23 is an anti-viral component of the Mediator complex that inhibits HSV-1 replication by directly interacting with transcription factor IRF7 to upregulate type III interferon (IFN-λ) expression; this anti-viral effect is specific to HSV-1 and does not extend to Vaccinia virus or Semliki Forest virus. Yeast two-hybrid (MED23-IRF7 interaction), RNAi screen, gain-of-function overexpression, IFN-λ mRNA/protein quantification PLoS pathogens Medium 23950709
2014 Liver-specific Med23 knockout improves glucose and lipid metabolism through modulating the transcriptional activity of FOXO1; MED23 participates in gluconeogenesis and cholesterol synthesis by facilitating Mediator and RNAPII recruitment to FOXO1 target gene promoters; this FOXO1-MED23 functional interaction is evolutionarily conserved in Drosophila fat body. Liver-specific Med23 knockout mouse, acute hepatic Med23 knockdown (db/db mice), ChIP, Drosophila genetic epistasis Cell research High 25223702
2014 T cell-specific deletion of Med23 leads to hyperactivation of T cells by reducing transcription of multiple negative regulators of T-cell activation; MED23 is required for full MEF2 transcription factor activity, which in turn drives expression of KLF2 (a T-cell master regulatory transcription factor), and loss of KLF2 in MED23-null T cells accounts for failure to populate peripheral lymphoid organs. Conditional Med23 knockout (Lck-Cre), gene expression profiling, functional assays in MED23-null MEFs for MEF2 activity Nature communications / PloS one Medium 25054639 25301163
2015 MED23 is required for H2B monoubiquitination at lysine 120 (H2Bub): MED23 physically associates with the RNF20/40 E3 ubiquitin ligase complex (identified by TAP-MS), and the Mediator complex directly and substantially increases H2Bub on recombinant chromatin in a cell-free system through cooperation with RNF20/40 and the PAF complex. MED23 depletion specifically reduces H2Bub on a subset of MED23-controlled genes genome-wide. Tandem affinity purification/mass spectrometry, cell-free reconstitution assay with recombinant chromatin, ChIP-seq, genome-wide histone modification profiling The EMBO journal High 26330467
2015 Med23 depletion enhances neural differentiation of murine ESCs by attenuating BMP signaling; mechanistically, MED23 modulates Bmp4 expression by controlling ETS1 transcription factor activity at the Bmp4 promoter-enhancer; med23 knockdown in zebrafish embryos also enhances neural development, reversed by co-injection of bmp4 mRNA. Med23 knockdown in ESCs, gene profiling, ChIP, minigene reporter, zebrafish morpholino knockdown with rescue Development (Cambridge, England) Medium 25564654
2016 MED23 physically binds RUNX2 and modulates its transcriptional activity during osteoblast differentiation; Med23 deletion in mesenchymal stem cells or osteoblast precursors reduces Runx2-target gene expression without changing Runx2 levels; Med23 deficiency exacerbates skeletal defects in Runx2+/- mice, establishing genetic interaction. Conditional Med23 knockout mice, in vitro differentiation assay, co-IP (MED23-RUNX2 binding), gene expression analysis, epistasis (Med23/Runx2 compound mutant) Nature communications High 27033977
2017 MED23 controls pigmentation and DNA repair through the transcription factor MITF: Med23 deficiency impairs pigmentation in melanocyte-lineage cells and zebrafish, and enhances nucleotide excision repair (NER) and reduces UV-induced DNA damage by increasing expression and chromatin recruitment of NER factors; MED23 modulates Mitf expression by controlling its distal enhancer activity. Med23 conditional knockout in melanocytes, zebrafish knockdown, NER assay, gene expression profiling, ChIP (Mitf enhancer activity) Cell reports Medium 28834744
2017 In C. elegans, SUR-2/MED23 and LIN-1/ELK1 (but not the Cdk8 kinase module) act together to promote endocytic downregulation of LIN-12/Notch-GFP in 1° VPCs and to resist LIN-12/Notch signaling when EGFR is active, integrating EGFR and Notch signaling in vulval precursor cell fate patterning. C. elegans genetics (sur-2, lin-1, Cdk8 module loss-of-function), cell fate reporter assays, LIN-12-GFP endocytosis assay Genetics Medium 28954762
2018 Med23 acts as a gatekeeper of the myeloid potential of hematopoietic stem cells (HSCs): Med23 ablation leads to myeloid-biased differentiation and loss of self-renewal; mechanistically, Med23 maintains stemness gene expression and suppresses myeloid lineage gene expression in HSCs. Hematopoietic-specific Med23 knockout mice, FACS, gene expression profiling Nature communications Medium 30218073
2019 MED23 suppresses liver fibrosis-related chemokine production (CCL5, CXCL10) by interacting with the orphan nuclear receptor RORα and facilitating G9a (EHMT2)-mediated H3K9 dimethylation at CCL5 and CXCL10 promoters; hepatic Med23 deletion aggravates CCl4-induced fibrosis with enhanced chemokine production and inflammatory infiltration. Liver-specific Med23 knockout mice, CCl4 fibrosis model, ChIP (H3K9me2), qRT-PCR, mechanistic reporter assays PLoS biology Medium 31805036
2020 Med23 binds to the promoter region of Sox9 and represses Sox9 expression in vitro; conditional loss of Med23 in mouse neural crest cells results in upregulated Sox9 and enhanced Sox9-β-catenin binding, leading to reduced Wnt signaling target gene expression, decreased proliferation, and craniofacial defects (micrognathia, cleft palate). Neural crest-specific Med23 conditional knockout (Wnt1-Cre), ChIP (MED23 at Sox9 promoter), in vitro reporter repression assay, co-IP (Sox9-β-catenin) Journal of dental research Medium 33155500
2020 Med23 deficiency in cranial placode-containing neural tissues is associated with elevated WNT/β-catenin signaling; partial rescue of cranial ganglia defects through combined Lrp6 and Wise loss-of-function places Med23 as a negative regulator of WNT signaling in placode neuronal differentiation. ENU forward genetic screen (snouty mutant), genetic mapping to Med23, phenotypic analysis, epistasis rescue with Lrp6/Wise loss-of-function Frontiers in physiology Medium 33192541
2022 Med23 maintains vascular integrity by negatively regulating angiopoietin2 (Ang2) expression; endothelial-specific Med23 deletion causes intracranial hemorrhage, impaired angiogenesis, and dilated vessels; knockdown in HUVECs recapitulates these defects cell-autonomously, and inhibition of Ang2 partially rescues angiogenic sprouting and lumen dilation defects. Endothelial-specific Med23 KO (embryonic lethal), HUVEC knockdown, RNA-seq, Ang2 inhibition rescue in tube formation assay Communications biology Medium 35440711
2022 The ELF3-MED23 protein-protein interaction is mediated by specific hydrogen bonds between residues D400 and H449 of MED23 and W138 and I140 of ELF3; this interaction drives HER2 gene transcription; small molecule YK1 disrupting these H-bonds attenuates HER2-mediated oncogenic signaling in vitro and in vivo. Fluorescence polarization binding assay, GST pulldown, LC-MS/MS quantitative assay, biosensor assay, in silico structural analysis, SEAP reporter, xenograft mouse model Journal of advanced research High 35963541
2024 Med23 controls oligodendrocyte differentiation and myelination by modulating Sp1-directed gene programs related to oligodendrocyte differentiation and cholesterol metabolism; mechanistically, Med23 modulates P300 binding to Sp1-targeted genes to orchestrate H3K27 acetylation and enhancer activation for oligodendrocyte lineage progression. Med23Q649R knock-in mouse, oligodendrocyte-lineage specific Med23 KO, in vitro differentiation assay, gene profiling, reporter assays, ChIP (P300, H3K27ac) Cell discovery High 39402028
2024 MED23 interacts with BCLAF1 (identified by Co-IP/mass spectrometry, confirmed by PLA assay); the MED23/BCLAF1 complex regulates expression of NUPR1 (validated by RNA-seq and ChIP); depletion of MED23 triggers premature senescence in NSCLC cells via disruption of autophagic flux downstream of NUPR1. Co-IP, mass spectrometry, proximity ligation assay (PLA), RNA-seq, ChIP Biochemical and biophysical research communications Medium 39366174
2024 Med23 controls muscle stem cell (MuSC) proliferation versus differentiation during muscle regeneration by oppositely regulating TCF/ELK1-SRF-targeted proliferation genes and MRTF-SRF-targeted myogenic differentiation genes; Med23 deficiency decreases ELK1/SRF binding at proliferation gene promoters and promotes MRTF-A/SRF binding at myogenic gene promoters. MuSC-specific Med23 KO mice, muscle injury model, myofiber culture, integrative genomics, ChIP (ELK1/SRF and MRTF-A/SRF) Cell reports High 38691453
2025 Med23 interacts with the transcription factor FOXO3 to negatively regulate RIG-I expression; Med23 deficiency markedly enhances IFN-I, proinflammatory cytokines, and ISG production in response to RNA virus VSV or poly(I:C); myeloid-specific Med23 KO mice show increased host resistance to VSV infection. Myeloid-specific Med23 KO mice, multiple cell lines and primary macrophages, co-IP (MED23-FOXO3), qRT-PCR, ELISA, viral challenge PLoS biology Medium 40705824
2025 MED23 collaborates with transcription factor RFX5 to regulate a novel enhancer for IGF2 expression; MED23 deficiency reduces NQO1 protein stability, leading to increased ROS and reduced hepatocyte viability; liver-specific Med23 ablation inhibits HCC development in DEN-induced mouse models. Constitutive and inducible liver-specific Med23 KO mice, DEN-HCC model, ChIP (RFX5/MED23 at IGF2 enhancer), NQO1 stability assay, ROS measurement, IGF2 overexpression rescue Cell death & disease Medium 41436431

Source papers

Stage 0 corpus · 42 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2003 Melanoma metastasis suppression by chromosome 6: evidence for a pathway regulated by CRSP3 and TXNIP. Cancer research 153 12543799
2012 Mediator complex regulates alternative mRNA processing via the MED23 subunit. Molecular cell 138 22264826
2009 Mediator MED23 links insulin signaling to the adipogenesis transcription cascade. Developmental cell 99 19460352
2013 A systematic analysis of host factors reveals a Med23-interferon-λ regulatory axis against herpes simplex virus type 1 replication. PLoS pathogens 90 23950709
2016 Mediator MED23 cooperates with RUNX2 to drive osteoblast differentiation and bone development. Nature communications 63 27033977
2014 Liver Med23 ablation improves glucose and lipid metabolism through modulating FOXO1 activity. Cell research 63 25223702
2012 Mediator MED23 plays opposing roles in directing smooth muscle cell and adipocyte differentiation. Genes & development 61 22972934
2004 MED16 and MED23 of Mediator are coactivators of lipopolysaccharide- and heat-shock-induced transcriptional activators. Proceedings of the National Academy of Sciences of the United States of America 59 15297616
2012 Selective requirement for Mediator MED23 in Ras-active lung cancer. Proceedings of the National Academy of Sciences of the United States of America 53 22988093
2017 Mediator Complex Subunits MED2, MED5, MED16, and MED23 Genetically Interact in the Regulation of Phenylpropanoid Biosynthesis. The Plant cell 50 29203634
2013 Mediator MED23 regulates basal transcription in vivo via an interaction with P-TEFb. Transcription 41 23340209
2015 The Mediator subunit MED23 couples H2B mono-ubiquitination to transcriptional control and cell fate determination. The EMBO journal 36 26330467
2015 MED23-associated intellectual disability in a non-consanguineous family. American journal of medical genetics. Part A 27 25845469
2014 The mediator subunit Med23 contributes to controlling T-cell activation and prevents autoimmunity. Nature communications 22 25301163
2017 Mediator MED23 Links Pigmentation and DNA Repair through the Transcription Factor MITF. Cell reports 18 28834744
2019 Mediator MED23 regulates inflammatory responses and liver fibrosis. PLoS biology 17 31805036
2017 Integration of EGFR and LIN-12/Notch Signaling by LIN-1/Elk1, the Cdk8 Kinase Module, and SUR-2/Med23 in Vulval Precursor Cell Fate Patterning in Caenorhabditis elegans. Genetics 17 28954762
2015 Mediator Med23 deficiency enhances neural differentiation of murine embryonic stem cells through modulating BMP signaling. Development (Cambridge, England) 17 25564654
2020 Med23 Regulates Sox9 Expression during Craniofacial Development. Journal of dental research 15 33155500
2019 Novel mutation in the MED23 gene for intellectual disability: A case report and literature review. Clinical case reports 14 30847200
2023 LINC00921 reduces lung cancer radiosensitivity by destabilizing NUDT21 and driving aberrant MED23 alternative polyadenylation. Cell reports 13 37999979
2020 Mediator Med23 Regulates Adult Hippocampal Neurogenesis. Frontiers in cell and developmental biology 12 32850819
2018 Med23 serves as a gatekeeper of the myeloid potential of hematopoietic stem cells. Nature communications 10 30218073
2013 Downregulation of MED23 promoted the tumorigenecity of esophageal squamous cell carcinoma. Molecular carcinogenesis 10 23625751
2020 The Mediator Subunit, Med23 Is Required for Embryonic Survival and Regulation of Canonical WNT Signaling During Cranial Ganglia Development. Frontiers in physiology 9 33192541
2024 Med23 deficiency reprograms the tumor microenvironment to promote lung tumorigenesis. British journal of cancer 8 38195889
2014 Upregulation of mediator MED23 in non-small-cell lung cancer promotes the growth, migration, and metastasis of cancer cells. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 8 25273169
2022 Med23 supports angiogenesis and maintains vascular integrity through negative regulation of angiopoietin2 expression. Communications biology 7 35440711
2022 Interrupting specific hydrogen bonds between ELF3 and MED23 as an alternative drug resistance-free strategy for HER2-overexpressing cancers. Journal of advanced research 7 35963541
2017 MED23 in endocrinotherapy for breast cancer. Oncology letters 7 28588722
2017 Differing roles for sur-2/MED23 in C. elegans and C. briggsae vulval development. Development genes and evolution 5 28220250
2014 T-cells null for the MED23 subunit of mediator express decreased levels of KLF2 and inefficiently populate the peripheral lymphoid organs. PloS one 5 25054639
2025 DNA hypermethylation of MED1 and MED23 as early diagnostic biomarkers for unsolved issues in atrial fibrillation. International journal of cardiology 3 40113094
2025 Central Med23 deficiency leads to malformation of dentate gyrus and ADHD-like behaviors in mice. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology 2 40114018
2024 Mediator MED23 controls oligodendrogenesis and myelination by modulating Sp1/P300-directed gene programs. Cell discovery 2 39402028
2015 MED23: a new Mediator of H2B monoubiquitylation. The EMBO journal 2 26438725
2025 Mediator complex subunit MED23 dampens antiviral innate immunity by restricting RIG-I expression. PLoS biology 1 40705824
2025 Targeting MED23 inhibits hepatocellular carcinoma development by suppressing compensatory proliferation and facilitating ROS-mediated cell death. Cell death & disease 1 41436431
2024 MED23 depletion induces premature senescence in NSCLC cells by interacting with BCLAF1 and then suppressing NUPR1 expression. Biochemical and biophysical research communications 1 39366174
2024 Synthesis and biological assessment of chalcone and pyrazoline derivatives as novel inhibitor for ELF3-MED23 interaction. eLife 1 39641248
2024 The Mediator Med23 controls a transcriptional switch for muscle stem cell proliferation and differentiation in muscle regeneration. Cell reports 0 38691453
2024 MED23 pathogenic variant: genomic-phenotypic analysis. Journal of medicine and life 0 39144687

Missed literature

Know a paper Affinage missed for MED23? Flag it for the maintainers and the community.

No submissions yet.