Affinage

MED25

Mediator of RNA polymerase II transcription subunit 9 · UniProt Q9NWA0

Length
146 aa
Mass
16.4 kDa
Annotated
2026-06-10
68 papers in source corpus 35 papers cited in narrative 35 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

MED25 is a subunit of the Mediator transcriptional coactivator that functions as a signal-specific docking hub, transducing activating signals from diverse DNA-bound transcription factors to RNA Polymerase II (PMID:14983011, PMID:21135126). Its central ACID/PTOV domain is a seven-stranded β-barrel framed by three helices that engages the acidic transactivation domains of activators on two distinct faces (the VP16 H1 and H2 pockets), a binding mode shared by VP16, the PEA3/ETS factors ERM/ETV4/ETV5, p53, ATF6α, and the viral protein NS1 (PMID:20974256, PMID:21378965, PMID:26130716, PMID:28728983, PMID:30360415). Activator TADs are intrinsically disordered and fold upon binding ACID to form fuzzy complexes (PMID:26130716), and MED25 can stimulate factor activity directly, as it relieves ETV4 autoinhibition to promote its DNA binding (PMID:28728983). The N-terminal VWA domain integrates MED25 into the Mediator complex (PMID:25792360), while a C-terminal LxxLL/NR-box motif recruits ligand-activated nuclear receptors including RAR/RXR, HNF4α, and ERα (PMID:17641689, PMID:22952853, PMID:24960263). Through these contacts MED25 enables preinitiation complex assembly and couples activators to chromatin modification, recruiting CBP/CREBBP to drive H3K27/H3K9 acetylation while its loss promotes PRC2-mediated repressive methylation (PMID:17641689, PMID:25391650). In plants, MED25 serves as an integrating node for jasmonate, ethylene, and light signaling, physically bridging MYC2/MYC3, EIN3/EIL1, and PIF4 transcription factors to chromatin where it directs histone acetylation, dynamic enhancer–promoter looping, and alternative splicing of target genes (PMID:31852773, PMID:28973940, PMID:31182849, PMID:36471914, PMID:32938743). MED25 also contributes to host antiviral defense, as it restricts respiratory syncytial virus replication and is targeted by RSV NS1, which competes with cellular activators for the ACID domain (PMID:36102648, PMID:35907573). MED25 abundance is itself tuned by a regulatory module in which the E3 ligases MBR1/2 promote VWA-dependent ubiquitin-proteasomal degradation, antagonized by MED16 (PMID:39824838).

Mechanistic history

Synthesis pass · year-by-year structured walk · 18 steps
  1. 2004 High

    Established that MED25 is a direct, functionally required transducer of an activator signal, defining its role as a Mediator-linked coactivator rather than a passive structural subunit.

    Evidence Affinity chromatography, co-IP, and siRNA knockdown with VP16 reporter assays in human cells

    PMID:14983011

    Open questions at the time
    • Did not resolve the structural basis of VP16 recognition
    • Did not define which other activators use MED25
  2. 2007 High

    Showed MED25 uses distinct domains for distinct partners, with a C-terminal LxxLL motif engaging ligand-activated nuclear receptors and the PTOV domain recruiting CBP for coactivation.

    Evidence Co-IP, ChIP, reporter assays, dominant-negative constructs, and siRNA in human cells (RAR/RXR)

    PMID:17641689

    Open questions at the time
    • Selectivity for RAR over thyroid receptor not structurally explained
    • CBP recruitment mechanism not mapped at residue level
  3. 2010 High

    Defined the ACID domain fold as a seven-stranded β-barrel and located the VP16 binding surface, providing the structural framework for activator recognition.

    Evidence NMR structure determination and chemical shift mapping; independently corroborated by a parallel NMR study and in vitro transcription

    PMID:20974256 PMID:21378965 PMID:21785987

    Open questions at the time
    • How two activator faces cooperate kinetically not fully resolved
    • Structures of full-length MED25 not determined
  4. 2010 High

    Demonstrated MED25 is required for HNF4α to assemble Mediator and recruit Pol II at a defined subset of metabolic target genes, linking the coactivator to selective gene programs.

    Evidence ChIP, co-IP, and gain/loss-of-function with expression profiling in human cells

    PMID:21135126

    Open questions at the time
    • Basis for gene-subset selectivity not defined
    • Direct vs Mediator-bridged contact not separated
  5. 2013 High

    Extended the activator repertoire to ETS/PEA3 factors and ATF6α and showed MED25 depletion disrupts their Mediator association, generalizing the ACID docking-site model across activator families.

    Evidence Pulldown, ChIP, reporter assays, mutagenesis, and siRNA; domain mapping for ATF6α

    PMID:23531547 PMID:23864652

    Open questions at the time
    • ATF6α study was a single lab with limited orthogonal validation
    • In vivo specificity among ETS family members not fully resolved
  6. 2014 High

    Connected MED25 activator function to chromatin state, showing it drives CBP-dependent H3K27 acetylation and that its loss shifts loci toward PRC2-mediated repressive methylation, plus a direct PIC-assembly requirement.

    Evidence ChIP, FAIRE, in vitro transcription reconstitution, and knockdown in human cells (HNF4α/CYP2C9)

    PMID:25391650

    Open questions at the time
    • Direct vs indirect PRC2 antagonism not separated
    • Generality beyond CYP2C9 not established
  7. 2012 High

    Showed MED25 is required for HNF4α-driven insulin secretion gene programs and that MODY-associated HNF4α mutations disrupt the interaction, linking the coactivator to physiology and disease.

    Evidence Yeast two-hybrid, co-IP, reporter assays, knockdown, mutagenesis, and insulin secretion assays in β-cells

    PMID:22952853

    Open questions at the time
    • MED25's own genetic contribution to MODY not tested
    • Ligand-independence vs nuclear-receptor LxxLL paradigm not reconciled
  8. 2015 High

    Resolved the molecular nature of activator binding as coupled folding into a fuzzy complex, identifying critical aromatic anchor residues and a shared binding pocket with VP16.

    Evidence NMR, mutagenesis, and competition binding for ERM/ETV5 TAD on MED25 ACID

    PMID:26130716

    Open questions at the time
    • Dynamics under transcription conditions not measured
    • Affinity differences among activators not quantified here
  9. 2014 Medium

    Established ERα as an additional ligand-dependent LxxLL partner required for receptor-driven transcription, reinforcing the C-terminal nuclear-receptor module.

    Evidence Co-IP, reporter assays, and expression analysis in human cells (estradiol and later BPA)

    PMID:24960263 PMID:27273787

    Open questions at the time
    • Single-lab Co-IP/reporter combinations without structural validation
    • Ligand-dependent vs independent binding modes not unified
  10. 2017 High

    Showed MED25 actively stimulates factor activity—relieving ETV4 autoinhibition to enhance DNA binding—and that ETS, FOS and JUN engage overlapping or adjacent ACID sites, revealing combinatorial activator integration.

    Evidence Biophysical binding, in vitro DNA binding, ChIP-seq, reporter assays, and mutagenesis

    PMID:28728983

    Open questions at the time
    • Stoichiometry of multi-factor co-occupancy in vivo not resolved
    • Mechanism of autoinhibition relief not structurally detailed
  11. 2018 Medium

    Added p53 to the set of activators recognized through the conserved ACID hydrophobic groove via its TAD2 amphipathic helix, supporting a unified recognition mechanism.

    Evidence NMR chemical shift perturbation, ITC, mutagenesis, and structural modeling

    PMID:30360415

    Open questions at the time
    • No in vivo functional validation of the p53-MED25 axis
    • Single-lab biophysical study
  12. 2015 Medium

    Pinpointed the VWA domain as the determinant of MED25 incorporation into Mediator using a disease-associated mutation that abolishes the interaction.

    Evidence Co-IP with a patient-derived p.(Tyr39Cys) VWA mutation in mammalian cells

    PMID:25792360

    Open questions at the time
    • Single-method evidence
    • Which Mediator subunits VWA contacts not identified
  13. 2019 High

    Defined MED25 as the central activator-integration node of plant jasmonate signaling, bridging MYC2 to chromatin and coupling it to histone acetylation, enhancer-promoter looping, and alternative splicing.

    Evidence Co-IP, ChIP/ChIP-seq, chromatin conformation capture, splicing assays, and loss-of-function mutants in Arabidopsis (MYC2, HAC1, COI1, LUH, PRP39a/PRP40a)

    PMID:28973940 PMID:31182849 PMID:31320481 PMID:31852773

    Open questions at the time
    • Whether splicing and looping functions are mechanistically coupled is unresolved
    • Conservation of these chromatin functions in mammalian MED25 not tested
  14. 2022 High

    Mapped a short MED25 binding domain (CMIDM) recognized by both MYC3 and EIN3/EIL1, providing a competition-based mechanism for cross-talk between jasmonate and ethylene signaling, and extended the activator-bridging role across light and developmental pathways.

    Evidence Quantitative biochemical binding, domain mapping, competition assays, plus Co-IP/ChIP-seq for PIF4 and DST modules across plant species

    PMID:32938743 PMID:34929168 PMID:35212455 PMID:35876657 PMID:36471914 PMID:36537119

    Open questions at the time
    • In vivo competition between EIN3/EIL1 and MYC not directly demonstrated
    • Whether one MED25 surface or several mediate these distinct factors not unified
  15. 2025 High

    Established a homeostatic control loop for MED25 abundance in which MBR1/2 E3 ligases drive VWA-dependent degradation antagonized by MED16, defining how coactivator dosage tunes transcriptional output.

    Evidence Co-IP, ubiquitination assays, genetic epistasis, and protein stability assays in Arabidopsis

    PMID:39824838

    Open questions at the time
    • Whether mammalian MED25 is regulated by an analogous module unknown
    • Signals controlling MBR1/2 activity not defined
  16. 2025 High

    Defined MED25 as a host antiviral factor and the target of RSV NS1, which straddles two ACID faces to competitively block cellular activators and reprogram host transcription via ATF3, attenuating interferon-stimulated gene responses.

    Evidence PPI screens, endogenous Co-IP, X-ray crystallography, NMR, mutagenesis, recombinant virus replication, ChIP-seq and RNA-seq in human cells

    PMID:35907573 PMID:36102648 PMID:40128225 PMID:40920851

    Open questions at the time
    • Full set of MED25-dependent antiviral target genes not defined
    • Whether NS1 binding alters Mediator integration not resolved
  17. 2024 Medium

    Provided proof of concept that the MED25 ACID H2 face is a druggable activator-interaction surface, with a lipopeptidomimetic that stabilizes MED25 and suppresses PPI-regulated genes in cancer cells.

    Evidence Binding affinity assays, structural mapping, proteome stabilization, and expression analysis in a triple-negative breast cancer model

    PMID:38527936

    Open questions at the time
    • Single-lab study without in vivo efficacy
    • Selectivity across the activator repertoire not fully characterized
  18. 2023 Medium

    Implicated MED25 as a negative regulator of adipogenesis, limiting C/EBPα and PPARγ induction, broadening its physiological roles beyond defined activator pathways.

    Evidence siRNA knockdown with adipogenesis and lipid accumulation assays in 3T3-L1 cells

    PMID:37047128

    Open questions at the time
    • Direct transcription factor target through which MED25 acts not identified
    • Mechanistic placement in adipogenic transcription circuit absent

Open questions

Synthesis pass · forward-looking unresolved questions
  • How MED25 selects among its many competing activator partners in a given cell, and whether its abundance-control and chromatin-remodeling functions are conserved between plant and mammalian systems, remains unresolved.
  • No structure of full-length MED25 within assembled Mediator
  • Rules governing competitive occupancy of ACID faces in vivo unknown
  • Conservation of MED16/MBR1-2 dosage control outside plants untested

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 5 GO:0140110 transcription regulator activity 5 GO:0098772 molecular function regulator activity 3
Localization
GO:0005634 nucleus 4 GO:0000228 nuclear chromosome 3
Pathway
R-HSA-162582 Signal Transduction 5 R-HSA-4839726 Chromatin organization 4 R-HSA-74160 Gene expression (Transcription) 4 R-HSA-168256 Immune System 3 R-HSA-8953854 Metabolism of RNA 1
Partners
CREBBPEIN3ESR1ETV4HNF4AMED16MYC2PIF4
Complex memberships
Mediator complex

Evidence

Reading pass · 35 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2004 ARC92 (MED25) is a direct and specific binding target of the VP16 transcriptional activation domain. It associates with VP16 activation domain both in vitro (affinity chromatography) and in vivo (co-IP), and siRNA-mediated knockdown of ARC92 selectively inhibits Gal4-VP16 gene activation, establishing MED25 as a functionally important transducer of VP16 activating signals to the RNA Pol II machinery. Affinity chromatography, peptide microsequencing, co-immunoprecipitation, siRNA knockdown with reporter gene assay Proceedings of the National Academy of Sciences of the United States of America High 14983011
2007 MED25 directly associates with retinoic acid receptor (RAR/RXR) through its C-terminal LxxLL (NR box) motif in a ligand-dependent manner, recruits CBP to the RARβ2 promoter, and enhances RAR/RXR-mediated transcription. Its PTOV domain mediates intrinsic transcriptional activity via direct association with CBP. MED25 knockdown selectively reduces RAR (but not thyroid hormone receptor) activity. Co-immunoprecipitation, chromatin immunoprecipitation (ChIP), reporter assays, dominant-negative constructs, siRNA knockdown The EMBO journal High 17641689
2010 The NMR structure of the MED25 ACID domain reveals a seven-stranded β-barrel with three α-helices, architecturally related to the SPOC domain superfamily. VP16 H2 (VP16C) interacts with MED25 ACID through one face of the β-barrel (strands B4-B7-B6). NMR structure determination, NMR chemical shift mapping Journal of structural biology High 20974256
2011 NMR structure of the MED25 ACID domain (also solved independently) confirms a seven-stranded β-barrel framed by three helices. The VP16 subdomains H1 and H2 bind to opposite faces of ACID and cooperate during promoter-dependent activated transcription in an in vitro transcription system. The activator-binding ACID faces are functionally required (mutation of these faces abolishes activation) and conserved among higher eukaryotes. NMR structure determination, in vitro transcription assay, site-directed mutagenesis of ACID binding faces Nature structural & molecular biology High 21378965
2011 Solution NMR structure of MED25(391-543) ACID domain is similar to β-barrel domains of human Ku and the SPOC domain of SHARP. The domain interacts with acidic transactivation domains of HSV-1 VP16 and VZV IE62. Solution NMR structure determination, backbone heteronuclear 15N-{1H} NOE measurements Journal of structural and functional genomics Medium 21785987
2010 MED25 (Med25) is required for HNF4α to associate with the Mediator complex and with RNA Pol II at target promoters. Modulation of Med25 levels alters composition of the transcriptional complex and Pol II recruitment, selectively affecting a subset of HNF4α target genes involved in drug and lipid metabolism. Chromatin immunoprecipitation, co-immunoprecipitation, siRNA knockdown and overexpression with gene expression analysis Molecular and cellular biology High 21135126
2013 MED25 plays a critical role in recruiting Mediator to ER stress response gene promoters via the transcription factor ATF6α. A specific MED25 domain serves as a docking site on Mediator for the ATF6α transcription activation domain. Co-immunoprecipitation, chromatin immunoprecipitation, domain-mapping experiments The Journal of biological chemistry Medium 23864652
2013 The N-terminal acidic transactivation domain (TAD) of PEA3 group ETS factors (PEA3, ERM, ER81) directly contacts the ACID/PTOV domain of MED25 to activate transcription. MED25 ACID domain depletion disrupts ERM-Mediator association in vitro. siRNA knockdown of MED25 inhibits PEA3-driven MMP-1 expression and Mediator recruitment. Mutations preventing MED25-ERM binding strongly reduce ERM transactivation. Pulldown, siRNA knockdown, reporter assay, chromatin immunoprecipitation, in vitro binding assays, mutagenesis Nucleic acids research High 23531547
2014 MED25 is required for HNF4α-mediated epigenetic regulation of CYP2C9. MED25 promotes H3K27 acetylation (via CREBBP/CBP) at the CYP2C9 promoter and its silencing leads to H3K27 trimethylation via Polycomb repressive complex 2 (PRC2). Silencing MED25 increases association of PRC2 with both CYP2C9 promoter chromatin and HNF4α itself. MED25 was shown to be required for full preinitiation complex assembly in vitro. ChIP, siRNA/shRNA knockdown, FAIRE chromatin accessibility assay, in vitro transcription reconstitution, co-immunoprecipitation The Journal of biological chemistry High 25391650
2012 MED25 interacts with HNF4α in pancreatic β-cells via an LXXLL motif in a ligand-independent manner, and this interaction is required for full activation of HNF4α-mediated transcription of genes driving glucose-stimulated insulin secretion. MODY mutations at the LXXLL-binding pocket of HNF4α disrupt this interaction and impair insulin secretion. Yeast two-hybrid, co-immunoprecipitation (in vivo and in vitro), reporter assays, siRNA/shRNA silencing, functional insulin secretion assay PloS one High 22952853
2015 The ERM/ETV5 TAD (ERM38-68) folds from a disordered state upon binding to MED25 ACID domain, forming a fuzzy complex. Two aromatic residues in ERM TAD (F47 and W57) are critical for binding and transactivation. The ERM TAD shares a common binding interface (VP16 H1 pocket, involving MED25 Q451) with VP16 H1. NMR spectroscopy (chemical shift perturbation, NOE), mutagenesis, competition binding experiments Nucleic acids research High 26130716
2016 Med25 acts as a coactivator of ligand-activated ERα, interacting with ERα through its C-terminal LXXLL motif after BPA exposure, and is functionally required for BPA-induced transcriptional activation of CYP2C9. Co-immunoprecipitation, reporter assays, gene expression analysis, ChIP Environmental toxicology Medium 27273787
2014 Med25 interacts with ERα through its C-terminal LXXLL motif in a ligand-dependent (17β-estradiol) manner and is required for ERα-mediated transcriptional activation of CYP2C9. Co-immunoprecipitation, reporter assays, gene expression analysis Biochemical pharmacology Medium 24960263
2017 ETV4 activation domain (AD) and DNA-binding domain (DBD) each independently bind MED25, with the DBD interacting with three MED25 sites allowing simultaneous binding of both domains. High-affinity MED25 interaction is specific to the ETV1/4/5 subfamily. MED25 stimulates ETV4 DNA binding in vitro by relieving autoinhibition. FOS strongly binds the same MED25 site as ETV4 AD; JUN interacts with the other two MED25 sites. NMR/biophysical binding assays, in vitro DNA binding assays, ChIP-seq, reporter assays, mutagenesis Journal of molecular biology High 28728983
2018 p53 transactivation domain (TAD) interacts with MED25 ACID domain primarily through the p53TAD2 sequence motif. An amphipathic α-helix of p53TAD2 binds an elongated hydrophobic groove of MED25 ACID, using a conserved mechanism shared with ERM TAD and VP16. NMR chemical shift perturbation, isothermal titration calorimetry (ITC), mutagenesis, structural modeling Molecules (Basel, Switzerland) Medium 30360415
2009 A missense mutation (p.A335V) in the proline-rich, SH3-binding region of MED25 causes decreased binding specificity, leading to recognition of a broader range of SH3 domain-containing proteins, implicating this domain in protein-protein interaction selectivity. Biochemical binding assays for SH3 domain interaction specificity, genetic linkage analysis Neurogenetics Low 19290556
2015 A homozygous mutation p.(Tyr39Cys) in the von Willebrand factor type A (VWA) domain of MED25 dramatically impairs MED25 interaction with the Mediator complex in mammalian cells, establishing that the VWA domain mediates MED25 recruitment into the Mediator complex. Co-immunoprecipitation in mammalian cells with patient-derived mutation Human genetics Medium 25792360
2010 PTOV1 competes with MED25 for binding to CBP, and the two proteins reciprocally regulate RAR transcriptional activity through competitive binding to CBP and opposite regulation of CBP recruitment to RA-responsive gene promoters. Co-immunoprecipitation, chromatin immunoprecipitation, reporter assays, competition binding experiments Biochemical and biophysical research communications Medium 21110951
2019 MED25 physically interacts with MYC2 and recruits it to JAZ gene promoters where it promotes alternative splicing of JAZ genes by recruiting the splicing factors PRP39a and PRP40a. JA-induced generation of dominant JAZ splice variants depends on MED25 and this MED25-PRP39a-PRP40a module prevents excessive desensitization of JA signaling. Co-immunoprecipitation, chromatin immunoprecipitation, genetic analysis, alternative splicing assays, loss-of-function mutants The Plant cell High 31852773
2017 Plant MED25 physically interacts with COI1 (jasmonate receptor F-box protein), brings COI1 to MYC2 target promoters, facilitates COI1-dependent JAZ repressor degradation, and physically and functionally interacts with histone acetyltransferase HAC1 to selectively promote H3K9 acetylation at MYC2 target promoters. MED25 and COI1 mutually influence each other's promoter enrichment. Co-immunoprecipitation, chromatin immunoprecipitation, genetic analysis, loss-of-function mutants, histone modification assays Proceedings of the National Academy of Sciences of the United States of America High 28973940
2019 MED25 is required for JA-regulated dynamic chromatin looping between jasmonate enhancers (JAEs) and their target gene promoters in a MED25-dependent manner. MED25 and MYC2 co-occupy JAEs genome-wide. ChIP-seq profiling of MYC2 and MED25, chromatin conformation capture (3C/Hi-C-type), loss-of-function mutants Nature plants High 31182849
2019 LEUNIG_HOMOLOG (LUH), a Gro/Tup1 family coregulator, is physically recruited by MED25 to MYC2 target promoters; LUH then links MYC2 with HAC1-dependent H3K9 acetylation to activate JAZ2 and LOX2. LUH promotes hormone-dependent enhancement of MYC2-MED25 and MYC2-HAC1 protein interactions. Co-immunoprecipitation, chromatin immunoprecipitation, bimolecular fluorescence complementation, loss-of-function mutants, reporter assays The Plant cell High 31320481
2021 A short binding domain of MED25 (CMIDM) is responsible for interaction with MYC3. The MYC3-MED25 interaction is bipartite and critical for stable complex formation. Binding affinity order established: JAZJas < MED25CMIDM < JAZCMID, providing a mechanism for transcriptional activation versus negative feedback regulation in JA signaling. Biochemical binding assays (cell-free protein synthesis), quantitative affinity measurements, domain mapping The Journal of biological chemistry Medium 34929168
2022 EIN3/EIL1 (ethylene signaling master transcription factors) interact with the same short binding domain of MED25 (CMIDM) as MYC3, suggesting that EIN3/EIL1 and MYC compete for binding to MED25, providing a molecular basis for coordination between ethylene and jasmonate signaling. Biochemical binding assays, domain mapping, competition binding experiments Bioscience, biotechnology, and biochemistry Medium 35876657
2025 MED16 stabilizes MED25 protein by competing with E3 ubiquitin ligases MBR1 and MBR2 for binding to the VWA domain of MED25, thereby antagonizing MBR1/2-mediated ubiquitin-proteasomal degradation of MED25. MED16 also promotes hormone-induced MYC2-MED25 interactions. Thus, the MED16-MBR1/2 module controls MED25 homeostasis to tune JA transcriptional output. Co-immunoprecipitation, ubiquitination assay, genetic epistasis, protein stability assays, domain mapping Nature communications High 39824838
2022 RSV nonstructural protein NS1 directly interacts with MED25, confirmed by co-immunoprecipitation during natural RSV infection with endogenous NS1. MED25 knockout A549 cells show enhanced RSV replication, indicating an antiviral role for MED25 during RSV infection. Three complementary PPI screens (BioID, MAPPIT, KISS), co-immunoprecipitation (overexpression and endogenous), MED25 knockout with viral replication assay Journal of virology High 36102648
2022 RSV NS1 directly interacts with the MED25 ACID domain in vitro and in cellula. The interaction involves the MED25 ACID H2 face (similarly to VP16 and ATF6α TADs) and the NS1 C-terminal α3 helix plus globular domain. NS1 competes with ATF6α TAD for binding to MED25 ACID. Yeast two-hybrid, in vitro binding assay, NMR chemical shift mapping, co-immunoprecipitation, competition binding assay Journal of molecular biology High 35907573
2025 X-ray crystal structure of the NS1-MED25 ACID complex reveals that NS1 straddles and binds two faces of MED25 ACID, a binding mode distinct from previously known viral activators. NS1 single mutations (E110A, I54A) reduce affinity for MED25 ACID, attenuate RSV replication, and enhance antiviral ISG expression. ChIP-seq and RNA-seq identified ATF3 as a mediator of NS1/Mediator/ATF3-dependent host gene regulation during RSV infection. X-ray crystallography, NMR, mutagenesis, recombinant virus replication assay, ChIP-seq, RNA-seq Nature communications High 40128225
2025 NS1 α/β core domain binds MED25 ACID cooperatively with NS1 α3 helix to achieve nanomolar affinity. The dual NS1 binding site on MED25 ACID overlaps with the two canonical TAD binding interfaces, confirmed by NMR and AlphaFold prediction. NS1 E110A mutation reduces NS1-MED25 affinity, attenuates RSV replication, and upregulates antiviral ISG15. In MED25 knockdown cells, differences between WT and NS1 mutant RSV are partially lost, supporting functional relevance of the NS1-MED25 interaction in controlling antiviral responses. NMR chemical shift perturbation, AlphaFold structural prediction, mutagenesis, in vitro binding assay, recombinant virus replication assay, MED25 knockdown with ISG expression readout PLoS pathogens High 40920851
2024 A lipopeptidomimetic (LPPM-8) selectively inhibits MED25 protein-protein interactions by engaging the H2 face of the MED25 ACID domain with >20-fold improved affinity over the peptide alone (Ki ~4 μM). This interaction stabilizes full-length MED25 in cells and inhibits expression of Med25-activator PPI-regulated genes in a triple-negative breast cancer cell model. Binding affinity assays, NMR/structural mapping, cellular proteome stabilization assay, gene expression analysis Angewandte Chemie (International ed. in English) Medium 38527936
2023 Tomato MED25 physically interacts with EIN3/EIL (EIL1) transcription factors and is required for preinitiation complex (PIC) formation during ethylene-induced gene transcription. The MED25-EIL1 module co-occupies promoters of ripening-related genes and orchestrates positive and negative feedback transcriptional circuits for ethylene homeostasis during fruit ripening. Co-immunoprecipitation, chromatin immunoprecipitation, ChIP-seq, loss-of-function mutants, reporter assays The Plant cell High 36471914
2023 MED25 physically interacts with both PIF4 and HDA9 (histone deacetylase 9) in Arabidopsis. MED25 is required for efficient binding of PIF4 to the YUCCA8 locus under warm temperatures (thermomorphogenesis) and for HDA9-mediated H2A.Z depletion at YUCCA8. MED25 also destabilizes HDA9 protein. Genetic analysis shows MED25 and HDA9 operate in the same pathway for hypocotyl elongation. Co-immunoprecipitation, chromatin immunoprecipitation, genetic epistasis analysis (double mutants), protein stability assay Plant physiology High 36537119
2020 Tomato MED25 physically interacts with PIF4 at promoter regions of PIF4 target genes and recruits RNA Pol II to induce gene transcription during shade-induced hypocotyl elongation. MED25 is required for PIF4-dependent transcriptional regulation of auxin biosynthesis and signaling genes under shade. Co-immunoprecipitation, chromatin immunoprecipitation, loss-of-function analysis, gene expression assays Plant physiology High 32938743
2022 Rice OsMED25 physically interacts with the zinc finger transcription factor DST at the promoter region of OsCKX2 and recruits RNA Pol II to activate OsCKX2 transcription. Genetic analysis shows OsMED25 acts in the same pathway as the DST-OsCKX2 module to regulate spikelet number. OsMED25 RNAi and osmed25 loss-of-function plants phenocopy dst mutants. Co-immunoprecipitation, chromatin immunoprecipitation, genetic epistasis, RNAi loss-of-function Journal of integrative plant biology High 35212455
2023 Med25 silencing in 3T3-L1 preadipocytes enhances lipid accumulation and super-induces the master adipogenic regulators C/EBPα and PPARγ during adipogenesis, establishing Med25 as a limiter of adipogenic potential. siRNA knockdown, adipogenesis induction assay, lipid accumulation measurement, gene expression analysis International journal of molecular sciences Medium 37047128

Source papers

Stage 0 corpus · 68 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2017 Mediator subunit MED25 links the jasmonate receptor to transcriptionally active chromatin. Proceedings of the National Academy of Sciences of the United States of America 155 28973940
2004 The activator-recruited cofactor/Mediator coactivator subunit ARC92 is a functionally important target of the VP16 transcriptional activator. Proceedings of the National Academy of Sciences of the United States of America 110 14983011
2019 MED25 connects enhancer-promoter looping and MYC2-dependent activation of jasmonate signalling. Nature plants 99 31182849
2011 Structure and VP16 binding of the Mediator Med25 activator interaction domain. Nature structural & molecular biology 96 21378965
2007 MED25 is distinct from TRAP220/MED1 in cooperating with CBP for retinoid receptor activation. The EMBO journal 75 17641689
2020 Mediator subunit MED25: at the nexus of jasmonate signaling. Current opinion in plant biology 73 32777679
2019 Mediator Subunit MED25 Couples Alternative Splicing of JAZ Genes with Fine-Tuning of Jasmonate Signaling. The Plant cell 72 31852773
2010 Autotaxin and lysophosphatidic acid1 receptor-mediated demyelination of dorsal root fibers by sciatic nerve injury and intrathecal lysophosphatidylcholine. Molecular pain 65 21062487
2019 LEUNIG_HOMOLOG Mediates MYC2-Dependent Transcriptional Activation in Cooperation with the Coactivators HAC1 and MED25. The Plant cell 64 31320481
2009 Identification of the variant Ala335Val of MED25 as responsible for CMT2B2: molecular data, functional studies of the SH3 recognition motif and correlation between wild-type MED25 and PMP22 RNA levels in CMT1A animal models. Neurogenetics 58 19290556
2010 Med25 is required for RNA polymerase II recruitment to specific promoters, thus regulating xenobiotic and lipid metabolism in human liver. Molecular and cellular biology 55 21135126
1998 Plasma copolymer surfaces of acrylic acid/1,7 octadiene: surface characterisation and the attachment of ROS 17/2.8 osteoblast-like cells. Biomaterials 54 9856582
2023 Tomato MED25 regulates fruit ripening by interacting with EIN3-like transcription factors. The Plant cell 46 36471914
2008 A paramutation phenomenon is involved in the genetics of maize low phytic acid1-241 (lpa1-241) trait. Heredity 40 18781168
2020 Mediator Subunit MED25 Physically Interacts with PHYTOCHROME INTERACTING FACTOR4 to Regulate Shade-Induced Hypocotyl Elongation in Tomato. Plant physiology 37 32938743
1995 Contributions of individual kringle domains toward maintenance of the chloride-induced tight conformation of human glutamic acid-1 plasminogen. Biochemistry 37 7626628
2017 ETV4 and AP1 Transcription Factors Form Multivalent Interactions with three Sites on the MED25 Activator-Interacting Domain. Journal of molecular biology 34 28728983
2010 NMR structure of the human Mediator MED25 ACID domain. Journal of structural biology 32 20974256
1999 Comparison of proliferation and growth of human keratinocytes on plasma copolymers of acrylic acid/1,7-octadiene and self-assembled monolayers. Journal of biomedical materials research 31 10487890
2012 Protective role of D-saccharic acid-1,4-lactone in alloxan induced oxidative stress in the spleen tissue of diabetic rats is mediated by suppressing mitochondria dependent apoptotic pathway. Free radical research 30 22239106
2013 Role for human mediator subunit MED25 in recruitment of mediator to promoters by endoplasmic reticulum stress-responsive transcription factor ATF6α. The Journal of biological chemistry 29 23864652
2018 The polynucleotide kinase 3'-phosphatase gene (PNKP) is involved in Charcot-Marie-Tooth disease (CMT2B2) previously related to MED25. Neurogenetics 28 30039206
2014 Homozygous missense mutation in MED25 segregates with syndromic intellectual disability in a large consanguineous family. Journal of medical genetics 28 25527630
2013 The Mediator complex subunit MED25 is targeted by the N-terminal transactivation domain of the PEA3 group members. Nucleic acids research 28 23531547
2011 D-saccharic acid-1,4-lactone ameliorates alloxan-induced diabetes mellitus and oxidative stress in rats through inhibiting pancreatic β-cells from apoptosis via mitochondrial dependent pathway. Toxicology and applied pharmacology 28 21982801
2015 Homozygous MED25 mutation implicated in eye-intellectual disability syndrome. Human genetics 26 25792360
2023 The Mediator complex subunit MED25 interacts with HDA9 and PIF4 to regulate thermomorphogenesis. Plant physiology 23 36537119
2016 Lysophosphatidic Acid Signaling through the Lysophosphatidic Acid-1 Receptor Is Required for Alveolarization. American journal of respiratory cell and molecular biology 23 27082727
2010 PTOV1 antagonizes MED25 in RAR transcriptional activation. Biochemical and biophysical research communications 23 21110951
2015 Characterization of ERM transactivation domain binding to the ACID/PTOV domain of the Mediator subunit MED25. Nucleic acids research 20 26130716
2010 The low phytic acid1-241 (lpa1-241) maize mutation alters the accumulation of anthocyanin pigment in the kernel. Planta 20 20191364
2003 Direct electrochemical detection of oligonucleotide hybridization on poly(5-hydroxy-1,4-naphthoquinone- co-5-hydroxy-3-thioacetic acid-1,4-naphthoquinone) film. Analytical chemistry 20 14640757
2012 Study of low phytic acid1-7 (lpa1-7), a new ZmMRP4 mutation in maize. The Journal of heredity 19 22563127
2011 Solution NMR structure of MED25(391-543) comprising the activator-interacting domain (ACID) of human mediator subunit 25. Journal of structural and functional genomics 18 21785987
2022 An Unexpected Encounter: Respiratory Syncytial Virus Nonstructural Protein 1 Interacts with Mediator Subunit MED25. Journal of virology 17 36102648
2022 Mediator complex subunit MED25 physically interacts with DST to regulate spikelet number in rice. Journal of integrative plant biology 16 35212455
2004 Reagentless amperometric detection of l-lactate on an enzyme-modified conducting copolymer poly(5-hydroxy-1,4-naphthoquinone-co-5-hydroxy-3-thioacetic acid-1,4-naphthoquinone). Biosensors & bioelectronics 16 15046766
2014 Epigenetic modification of histone 3 lysine 27: mediator subunit MED25 is required for the dissociation of polycomb repressive complex 2 from the promoter of cytochrome P450 2C9. The Journal of biological chemistry 15 25391650
2011 Prophylactic role of D-Saccharic acid-1,4-lactone in tertiary butyl hydroperoxide induced cytotoxicity and cell death of murine hepatocytes via mitochondria-dependent pathways. Journal of biochemical and molecular toxicology 15 21538728
2009 Determination of D-saccharic acid-1,4-lactone from brewed kombucha broth by high-performance capillary electrophoresis. Journal of chromatography. B, Analytical technologies in the biomedical and life sciences 15 20015711
2012 MED25 is a mediator component of HNF4α-driven transcription leading to insulin secretion in pancreatic beta-cells. PloS one 14 22952853
2018 Structural Basis for the Interaction between p53 Transactivation Domain and the Mediator Subunit MED25. Molecules (Basel, Switzerland) 13 30360415
2018 Nitrous oxide emissions from the urine of beef cattle as regulated by dietary crude protein and gallic acid1. Journal of animal science 13 31986205
2013 The prophylactic role of D-saccharic acid-1,4-lactone against hyperglycemia-induced hepatic apoptosis via inhibition of both extrinsic and intrinsic pathways in diabetic rats. Food & function 13 23138840
2022 Respiratory Syncytial Virus NS1 Protein Targets the Transactivator Binding Domain of MED25. Journal of molecular biology 12 35907573
2025 A multiprotein regulatory module, MED16-MBR1&2, controls MED25 homeostasis during jasmonate signaling. Nature communications 11 39824838
2021 Protein-protein interactions between jasmonate-related master regulator MYC and transcriptional mediator MED25 depend on a short binding domain. The Journal of biological chemistry 11 34929168
2018 COQ8A and MED25 Mutations in a Child with Intellectual Disability, Microcephaly, Seizures, and Spastic Ataxia: Synergistic Effect of Digenic Variants? Molecular syndromology 11 30800049
2016 Upregulation of human CYP2C9 expression by Bisphenol A via estrogen receptor alpha (ERα) and Med25. Environmental toxicology 11 27273787
2014 Med25 is required for estrogen receptor alpha (ERα)-mediated regulation of human CYP2C9 expression. Biochemical pharmacology 7 24960263
2006 Solvent sublation and spectrometric determination of iron(II) and total iron using 3-(2-pyridyl)-5,6-bis(4-phenylsulfonic acid)-1,2,4-triazine and tetrabutylammonium bromide. Analytical sciences : the international journal of the Japan Society for Analytical Chemistry 7 16966804
2023 Cooperative Lewis Acid-1,2,3-Triazolium-Aryloxide Catalysis: Pyrazolone Addition to Nitroolefins as Entry to Diaminoamides. Angewandte Chemie (International ed. in English) 6 37358186
2022 Coordinately regulated transcription factors EIN3/EIL1 and MYCs in ethylene and jasmonate signaling interact with the same domain of MED25. Bioscience, biotechnology, and biochemistry 5 35876657
2023 Med25 Limits Master Regulators That Govern Adipogenesis. International journal of molecular sciences 4 37047128
2020 Improving the phenotype description of Basel-Vanagaite-Smirin-Yosef syndrome, MED25-related: polymicrogyria as a distinctive neuroradiological finding. Neurogenetics 4 32816121
2018 Origin and age of the causative mutations in KLC2, IMPA1, MED25 and WNT7A unravelled through Brazilian admixed populations. Scientific reports 4 30410084
2017 Papillae formation on trichome cell walls requires the function of the mediator complex subunit Med25. Plant molecular biology 4 28889249
2016 Design, semisynthesis and cytotoxic activity of novel ester derivatives of betulinic acid-1,2,4 oxadiazoles. Journal of Asian natural products research 4 27314626
2015 Polymorphisms in the retinoic acid-1 like-receptor family of genes and their association with clinical outcome of dengue virus infection. Archives of virology 4 25850761
2025 Molecular basis for human respiratory syncytial virus transcriptional regulator NS1 interactions with MED25. Nature communications 2 40128225
2025 TurboID-Based Proximity Labelling Identifies MED25 as an Activator of GoPGF-Mediated Gland Formation and Gossypol Biosynthesis in Cotton. Plant, cell & environment 2 40545710
2024 Design, synthesis, and antiproliferative evaluation of novel dehydroabietic acid-1,2,3-triazole-oxazolidinone hybrids. RSC medicinal chemistry 2 38389893
2024 A Lipopeptidomimetic of Transcriptional Activation Domains Selectively Disrupts the Coactivator Med25 Protein-Protein Interactions. Angewandte Chemie (International ed. in English) 2 38527936
2020 Multivalent and Bidirectional Binding of Transcriptional Transactivation Domains to the MED25 Coactivator. Biomolecules 2 32825095
2026 Design, synthesis, and antibacterial efficacy of new methylene disalicylic acid/1,3,4-oxadiazole hybrids as dual inhibitors of DNA gyrase and topoisomerase IV. Molecular diversity 0 41733769
2025 Unraveling the pathogenicity role of the novel compound heterozygous mutations of MED25 gene in a Chinese patient with BVSYS. Frontiers in genetics 0 40909439
2025 A dual interaction between RSV NS1 and MED25 ACID domain reshapes antiviral responses. PLoS pathogens 0 40920851
2023 A lipopeptidomimetic of transcriptional activation domains selectively disrupts Med25 PPIs. bioRxiv : the preprint server for biology 0 36993479

Missed literature

Know a paper Affinage missed for MED25? Flag it for the maintainers and the community.

No submissions yet.