Affinage

MED15

Mediator of RNA polymerase II transcription subunit 15 · UniProt Q96RN5

Length
788 aa
Mass
86.8 kDa
Annotated
2026-04-28
64 papers in source corpus 24 papers cited in narrative 24 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

MED15 is a tail-module subunit of the Mediator co-activator complex that serves as a critical interface between DNA-bound transcription factors and the RNA Pol II machinery, with conserved roles in lipid metabolism, stress responses, innate immunity, and developmental gene regulation. Its N-terminal KIX domain and additional activator-binding domains (ABDs) engage intrinsically disordered acidic activation domains of diverse transcription factors—including Gcn4, Gal4, Oaf1, Hsf1, SREBP1/2, Nkx6-1, and NeuroD1—through a sequence-independent 'fuzzy' hydrophobic binding mechanism, as demonstrated by NMR structural studies and functional mutagenesis (PMID:22195967, PMID:33850123, PMID:19056732, PMID:39379383). MED15 undergoes CDK1-mediated phosphorylation at T603 downstream of TGF-β, which disrupts FOXA1 binding and de-represses senescence-associated secretory phenotype (SASP) genes; a non-phosphorylatable T603A knock-in in aging mice attenuates SASP and improves cognition (PMID:40825935). MED15 also forms phase-separated nuclear condensates via its glutamine-rich intrinsically disordered region and hydrophobic motif, and its polyglutamine tract composition modulates activator interaction strength and transcriptional output (PMID:34789250, PMID:39717019).

Mechanistic history

Synthesis pass · year-by-year structured walk · 21 steps
  1. 2006 Medium

    Establishing that MED15 protein levels are actively regulated: TRIM11 was shown to promote ubiquitin-proteasome-dependent degradation of MED15, providing the first evidence that MED15 abundance is post-translationally controlled and linking this to attenuation of TGF-β-induced transcription.

    Evidence Co-immunoprecipitation, ubiquitination assay, proteasome inhibitor treatment, and reporter assays in mammalian cells

    PMID:16904669

    Open questions at the time
    • Reciprocal co-IP and endogenous interaction not shown
    • Physiological contexts triggering TRIM11-mediated MED15 turnover undefined
    • Ubiquitination sites on MED15 not mapped
  2. 2008 High

    Identifying the KIX domain as a conserved activator-docking site: the KIX domain of yeast Gal11/MED15 was shown to be required for fatty acid-dependent transcriptional activation by the PPAR-α analog Oaf1p, establishing MED15 as a key coactivator for ligand-dependent metabolic transcription factors.

    Evidence NMR spectroscopy of Oaf1p AD–KIX interaction, genetic deletion mutants, and transcriptional reporter assays in yeast

    PMID:19056732

    Open questions at the time
    • Mammalian PPAR–MED15 KIX interaction not directly tested
    • Structural details of KIX-Oaf1p interface not fully resolved
  3. 2009 High

    Revealing that MED15 uses multiple binding surfaces for activator recruitment: three distinct N-terminal segments (KIX, B-box, and a third region) of Med15 additively contribute to Gcn4-mediated Mediator recruitment in vivo, showing that activator engagement is not limited to a single domain.

    Evidence ChIP, NMR chemical shift perturbation, mutagenesis, and in vitro binding assays in yeast

    PMID:19940160

    Open questions at the time
    • Relative quantitative contribution of each ABD in different promoter contexts unknown
    • Whether mammalian MED15 retains all three binding surfaces not tested
  4. 2010 Medium

    Extending MED15 function to metazoan developmental signaling: Drosophila Med15 was shown to be required for Dpp (TGF-β/BMP) target gene expression during wing development, establishing an in vivo developmental role.

    Evidence Genetic mosaic screen and loss-of-function clonal analysis in Drosophila wing disc

    PMID:20233856

    Open questions at the time
    • Direct physical interaction between Med15 and Dpp pathway effectors (Mad/Medea) not shown
    • Mechanism of Med15 recruitment to Dpp target promoters unclear
  5. 2011 High

    Defining the structural basis of 'fuzzy' activator binding: NMR revealed that Gcn4's acidic activation domain binds Med15 ABD1 through a dynamic hydrophobic interface with no single fixed conformation, establishing the paradigm that activation domains engage Mediator through a conformational cloud rather than a lock-and-key fit.

    Evidence NMR structure of Gcn4 AD–ABD1 complex, mutagenesis, and yeast functional assays

    PMID:22195967

    Open questions at the time
    • Whether fuzzy binding applies to all Med15 activator partners unknown
    • Energetic contribution of individual hydrophobic contacts not fully dissected
  6. 2013 High

    Demonstrating cooperative Mediator recruitment during stress: Med15 and Med16 were shown to cooperatively recruit Mediator to heat shock promoters through Hsf1's dual activation domains, with double deletion abolishing both Mediator and Pol II occupancy, revealing tail-module subunit cooperativity in stress-responsive transcription.

    Evidence ChIP with single and double deletion mutants, Mediator and Pol II occupancy measurements in yeast

    PMID:23447536

    Open questions at the time
    • Structural basis of Hsf1–Med15 vs. Hsf1–Med16 interaction not resolved
    • Post-translational modifications of Med15 during heat shock not examined
  7. 2013 Medium

    Connecting MED15 to cell cycle control: yeast Med15 inactivation caused G1 arrest and downregulation of Ace2-dependent genes, and synthetic lethality of med15 with med5 or med16 indicated essential tail-module functions beyond simple activator bridging.

    Evidence N-Degron temperature-sensitive mutants, genome-wide expression profiling, and cell cycle analysis in yeast

    PMID:23991176

    Open questions at the time
    • Direct Ace2–Med15 physical interaction not demonstrated
    • Whether G1 arrest is a direct or indirect consequence of Med15 loss unclear
  8. 2013 Medium

    Implicating MED15 in TGF-β/SMAD signaling and cancer proliferation: MED15 knockdown in prostate cancer cells reduced p-SMAD3 nuclear shuttling and TGF-β-enhanced proliferation, positioning MED15 as a functional node in oncogenic TGF-β signaling.

    Evidence siRNA/shRNA knockdown, proliferation assays, p-SMAD3 immunostaining, and nuclear fractionation in prostate cancer cells

    PMID:24374838

    Open questions at the time
    • Direct MED15–SMAD3 physical interaction not shown
    • Whether MED15 acts on SMAD3 phosphorylation or nuclear import specifically not resolved
  9. 2014 Medium

    Broadening MED15's role to innate immunity and xenobiotic defense: C. elegans MDT-15 was required for p38/PMK-1-dependent immune gene induction and xenobiotic detoxification, linking MED15's metabolic coactivator function to pathogen defense.

    Evidence RNAi knockdown, qRT-PCR, and Pseudomonas aeruginosa infection survival assays in C. elegans

    PMID:24875643

    Open questions at the time
    • Direct MDT-15–PMK-1 interaction not established
    • Mammalian relevance of this immune role not tested
  10. 2014 Medium

    Validating MED15 as a human coactivator at endogenous promoters: MED15 knockdown in HeLa cells reduced VP16- and SREBP1a-mediated transcription, and ChIP placed MED15 at the p21 promoter alongside TFIIE and TFIIH, confirming its coactivator function in human cells.

    Evidence siRNA knockdown with rescue, immunostaining, and ChIP in HeLa cells

    PMID:25382556

    Open questions at the time
    • Whether MED15 directly contacts TFIIE/TFIIH or is in the same promoter complex indirectly not distinguished
    • Genome-wide target repertoire in human cells not defined
  11. 2019 High

    Revealing a conserved metal stress response function: MDT-15/MED15 physically interacted with nuclear hormone receptor HIZR-1 to drive zinc/cadmium-responsive gene expression in C. elegans, and human MED15 was required for metallothionein gene induction in cadmium-exposed lung cancer cells, establishing cross-species conservation.

    Evidence Yeast two-hybrid, qRT-PCR, reporter assays, ChIP in mammalian cells, and C. elegans loss-of-function mutants

    PMID:31815936

    Open questions at the time
    • Whether MED15 KIX domain mediates HIZR-1 binding not tested
    • Mammalian nuclear receptor partner for metal response not identified
  12. 2021 High

    Generalizing the fuzzy binding paradigm: NMR showed that Gal4 and Gcn4 activation domains, despite unrelated sequences, engage Med15 through nearly identical hydrophobic-cloud mechanisms, establishing sequence-independent activator recognition as a fundamental Mediator property.

    Evidence Comparative NMR chemical shift perturbation of Gal4 AD and Gcn4 AD binding to Med15

    PMID:33850123

    Open questions at the time
    • Whether mammalian activators use the same fuzzy mechanism with human MED15 not directly shown
    • Thermodynamic parameters of fuzzy vs. structured binding not compared
  13. 2021 Medium

    Discovering MED15 phase separation capacity: the glutamine-rich IDR and a downstream hydrophobic motif of MED15 drive formation of liquid-like nuclear condensates with rapid FRAP recovery, sensitive to hexanediol and DYRK3 kinase, introducing a biophysical dimension to MED15 coactivator function.

    Evidence Live cell imaging, FRAP, 1,6-hexanediol treatment, optodroplet assay, and DYRK3 overexpression in mammalian cells

    PMID:34789250

    Open questions at the time
    • Whether MED15 condensates contain active transcription machinery not shown
    • In vivo transcriptional relevance of condensate formation not demonstrated
  14. 2021 Medium

    Identifying prion-like aggregation potential: the MED15 prion-like domain forms amyloid-like aggregates via a coiled-coil-to-β-sheet transition that can sequester endogenous MED15, suggesting a pathological aggregation risk.

    Evidence Biochemical aggregation assays, coiled-coil disruption mutagenesis, and cell imaging in human cells

    PMID:33772081

    Open questions at the time
    • Physiological or disease relevance of PrLD aggregation not established
    • Whether aggregation occurs at endogenous expression levels unknown
  15. 2024 Medium

    Establishing MED15 as a direct coactivator of SREBP-dependent lipogenesis in cancer: MED15 physically interacted with SREBP1/2 and promoted lipid biosynthesis gene expression in renal cell carcinoma, with HIF-2α transcriptionally activating MED15 expression, placing MED15 in a HIF-2α→MED15→SREBP lipogenic axis.

    Evidence Co-immunoprecipitation, ChIP, siRNA knockdown, overexpression, and reporter assays in renal cancer cells

    PMID:38649345

    Open questions at the time
    • Which MED15 domain mediates SREBP binding not mapped
    • Whether MED15–SREBP interaction is direct or Mediator-complex-mediated not distinguished
  16. 2024 High

    Defining a β-cell maturation role: Med15 binds β-cell transcription factors Nkx6-1 and NeuroD1 and occupies their target loci; conditional knockout in mouse β-cells impairs maturation without affecting mass or insulin expression, and MED15 overexpression in human ESC-derived β-like cells enhances maturation markers.

    Evidence ChIP-seq, co-immunoprecipitation, conditional knockout mouse, and human ESC overexpression model

    PMID:39379383

    Open questions at the time
    • Which MED15 domain engages Nkx6-1 and NeuroD1 not mapped
    • Whether MED15 condensate formation is relevant to β-cell maturation unknown
  17. 2024 Medium

    Revealing intrinsic chromatin-targeting ability: Med15 shows inherent preference for 'fuzzy-nucleosome' promoter architecture independent of promoter-bound transcription factors, suggesting Med15 actively contributes to Mediator target site selection rather than passively following activators.

    Evidence ChIP-seq with DBD-Med15 fusion proteins and transcriptional assays in budding yeast

    PMID:39187372

    Open questions at the time
    • Molecular basis of fuzzy-nucleosome recognition by Med15 not determined
    • Whether mammalian MED15 shows similar chromatin preferences untested
  18. 2024 Medium

    Uncovering polyQ tract modulation of coactivator function: Med15 polyglutamine tract composition and length modulate ABD activity and transcription factor interaction strength, with the Q1 tract required for robust Msn2-Med15 interaction and phosphorylation affecting KIX domain activities.

    Evidence Phenotypic assays, gene expression analysis, and transcription factor interaction assays with defined polyQ mutants in yeast

    PMID:39717019

    Open questions at the time
    • Kinase(s) responsible for Med15 phosphorylation affecting KIX not identified in this context
    • Whether polyQ length variation in human MED15 has functional consequences unknown
  19. 2024 Medium

    Connecting MED15 to nuclear actin-dependent heat shock gene regulation: Drosophila Moesin directly binds Med15 and, together with Hsf and monomeric actin, forms a nuclear complex at Hsp gene regulatory regions; this interaction is conserved in human orthologs.

    Evidence Reciprocal co-immunoprecipitation, ChIP, RNAi knockdown, and direct binding assays in Drosophila and human cells

    PMID:39353569

    Open questions at the time
    • Which Med15 domain binds Moesin not mapped
    • Functional significance of actin in this complex not mechanistically resolved
  20. 2025 High

    Decoding a phospho-switch controlling senescence: TGF-β-induced CDK1-mediated phosphorylation of MED15 at T603 disrupts FOXA1 binding, releasing repression of SASP genes; a T603A knock-in in aging mice attenuates SASP and improves cognition, establishing a direct post-translational mechanism linking MED15 to aging.

    Evidence Phospho-mutagenesis (T603A/T603D), co-immunoprecipitation, in vivo knock-in mouse model, behavioral assays, and gene expression analysis

    PMID:40825935

    Open questions at the time
    • Whether T603 phosphorylation affects MED15 condensate formation unknown
    • How CDK1 specificity for MED15 is achieved in the TGF-β context not resolved
  21. 2025 Medium

    Revealing a non-transcriptional role in YAP1 stabilization: MED15 interacts with YAP1 and attenuates TRIM11-mediated YAP1 ubiquitination, promoting EMT; under stress, MED15 forms condensates with increased YAP1 colocalization, suggesting a phase-separation-dependent protein stabilization function.

    Evidence Co-immunoprecipitation, ubiquitination assay, siRNA knockdown, migration assays, and condensate imaging in bladder cancer cells

    PMID:41685983

    Open questions at the time
    • Whether MED15–YAP1 interaction is direct or bridged by other factors not resolved
    • Transcription-dependent vs. -independent contributions to EMT not separated

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include: how MED15 condensate formation relates to transcriptional activation at specific loci; whether fuzzy activator binding operates through the same ABD surfaces in mammals; how polyQ tract variation in human MED15 affects disease susceptibility; and the structural basis of MED15 engagement with metazoan-specific partners such as SMADs, SREBPs, and Nkx6-1.
  • No reconstituted transcription assay linking MED15 condensates to transcriptional output
  • No high-resolution structure of mammalian MED15 with any activator
  • Disease-causative mutations in human MED15 not identified

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 8 GO:0060090 molecular adaptor activity 4
Localization
GO:0005634 nucleus 3 GO:0005654 nucleoplasm 2
Pathway
R-HSA-74160 Gene expression (Transcription) 8 R-HSA-1430728 Metabolism 3 R-HSA-162582 Signal Transduction 3 R-HSA-8953897 Cellular responses to stimuli 3
Partners
FOXA1MSNNEUROD1NKX6-1SREBP1SREBP2TRIM11YAP1
Complex memberships
Mediator complex (tail module)

Evidence

Reading pass · 24 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2011 The acidic activation domain of transcription activator Gcn4 binds the Mediator subunit Gal11/Med15 activator-binding domain 1 (ABD1) through a 'fuzzy' protein interface: ABD1 has a four-helix fold with a shallow hydrophobic cleft, and eight residues of Gcn4 adopt a helical conformation allowing three aromatic/aliphatic residues to insert into the cleft via hydrophobic interactions only, with no single fixed conformation (fuzzy complex). Functional mutagenesis in yeast confirmed the importance of interface residues for transcriptional activation. NMR structure determination of bound complex + mutagenesis + yeast functional assays Molecular cell High 22195967
2008 The yeast Mediator subunit Gal11p/MED15 and its KIX domain is required for fatty acid-dependent transcriptional activation by the yeast PPAR-alpha analog Oaf1p. NMR spectroscopy showed that the Oaf1p activation domain interacts with the Gal11p/MED15 KIX domain in a manner similar to the zinc cluster family member Pdr1p, identifying the KIX domain as a key target of ligand-dependent transcription factors. NMR spectroscopy + genetic loss-of-function (deletion mutants) + transcriptional reporter assays The Journal of biological chemistry High 19056732
2009 Gcn4 recruits Mediator to target promoters in vivo through additive contributions from three distinct N-terminal segments of Gal11/Med15: the KIX domain, a B-box region (conserved with mammalian SRC-1), and a third segment. NMR chemical shift analysis identified the Gcn4 binding site on the KIX domain surface, and mutational studies showed B-box is a critical determinant of Mediator recruitment. In vitro binding assays + ChIP (chromatin immunoprecipitation) + NMR chemical shift perturbation + mutagenesis The Journal of biological chemistry High 19940160
2013 Med15 and Med16 are two Mediator tail subunits required for heat shock factor 1 (Hsf1)-dependent recruitment of Mediator to HSP gene promoters upon heat stress. Dual activation domains of Hsf1 cooperatively recruit holo-Mediator through the Tail module; loss of Med15 or Med16 individually reduces Mediator occupancy while loss of both abolishes it and substantially diminishes RNA Pol II recruitment. ChIP (chromatin immunoprecipitation) + genetic deletion mutants + Mediator/Pol II recruitment assays in yeast The Journal of biological chemistry High 23447536
2021 The acidic activation domains of both Gal4 and Gcn4, which are intrinsically disordered and of different sequence, interact with Med15 using nearly identical 'fuzzy' binding mechanisms as shown by NMR chemical shift perturbation analysis. This reveals a common sequence-independent mechanism for activation domain–Mediator binding through a hydrophobic cloud, distinct from the structured complex formed by Gal4 AD with its repressor Gal80. NMR chemical shift perturbation analysis of Gal4 AD and Gcn4 AD binding to Med15 Nature communications High 33850123
2006 TRIM11 physically interacts with MED15 (ARC105) and promotes its ubiquitin-proteasome-dependent degradation. Co-expression of TRIM11 increases ARC105 ubiquitination and degradation (blocked by proteasome inhibitor), and suppresses ARC105-mediated TGF-beta-induced transcriptional activation in reporter assays. Co-immunoprecipitation + ubiquitination assay + proteasome inhibitor treatment + transcriptional reporter assay FEBS letters Medium 16904669
2013 Inactivation of Med15 in yeast leads to down-regulation of Ace2 transcriptional activator target genes and a G1 cell cycle arrest phenotype. Synthetic lethality of med5/med15 and med15/med16 double mutations indicates that the Mediator Tail performs essential functions even as a separate complex. N-Degron temperature-sensitive mutants + genome-wide expression profiling + cell cycle analysis PloS one Medium 23991176
2014 The C. elegans MDT-15/MED15 ortholog is required for xenobiotic-induced expression of p38 MAP kinase (PMK-1)-dependent immune effector genes and detoxification genes, linking xenobiotic detoxification to innate immunity; RNAi knockdown of mdt-15 abrogates induction of PMK-1-dependent immune genes and increases susceptibility to Pseudomonas aeruginosa infection. RNAi screen + qRT-PCR + infection survival assays in C. elegans PLoS pathogens Medium 24875643
2014 Human MED15 promotes transcriptional activation by VP16 and SREBP1a in HeLa cells, as shown by siRNA knockdown (reducible by overexpression rescue). MED15 colocalizes with general transcription factors TFIIE and TFIIH in the nucleus, and ChIP shows MED15 localizes to both the p53 binding site and the p21 promoter region along with TFIIE and TFIIH upon Nutlin-3 treatment. siRNA knockdown + overexpression rescue + immunostaining colocalization + ChIP Drug discoveries & therapeutics Medium 25382556
2013 MED15 knockdown in prostate cancer cells reduces phosphorylation and nuclear shuttling of p-SMAD3 and attenuates TGF-beta-enhanced proliferation, indicating MED15 is required for TGF-beta/SMAD3 signaling. MED15 knockdown also decreases both androgen-dependent and -independent proliferation. siRNA/shRNA knockdown + proliferation assays + p-SMAD3 immunostaining + nuclear fractionation International journal of cancer Medium 24374838
2019 C. elegans MDT-15 physically interacts with nuclear hormone receptor HIZR-1 to promote zinc and cadmium stress-responsive gene expression; this interaction is enhanced by zinc or cadmium. mdt-15 and hizr-1 cooperate to regulate zinc storage in the gut and protect against zinc/cadmium toxicity. Mammalian MED15 orthologs bind genomic regulatory regions of metallothionein and zinc transporter genes in a cadmium/zinc-stimulated manner, and human MED15 is required for metallothionein gene induction in lung adenocarcinoma cells exposed to cadmium. Yeast two-hybrid + qRT-PCR + reporter assays + ChIP (mammalian cells) + loss-of-function mutants in C. elegans PLoS genetics High 31815936
2021 The human MED15 prion-like domain (PrLD) forms homodimers sustained by coiled-coil (CC) interactions, and this CC fold mediates transition to a beta-sheet amyloid state; disruption of the CC abolishes aggregation. Expression of MED15-PrLD in human cells promotes cytoplasmic and perinuclear inclusions that sequester endogenous full-length MED15 in a prion-like manner. Biochemical aggregation assays + mutagenesis (CC disruption) + cell imaging + bioinformatics of PrLD Communications biology Medium 33772081
2021 Med15 forms nuclear condensates (foci) in mammalian cells through its glutamine-rich intrinsically disordered region (IDR) and a short downstream hydrophobic motif. Med15 foci are sensitive to 1,6-hexanediol, show rapid FRAP recovery consistent with phase separation, and are disrupted by overexpression of DYRK3 kinase. Both the IDR and C-terminal region contribute to intracellular phase separation as shown by optodroplet assay. Live cell imaging + FRAP + 1,6-hexanediol treatment + optodroplet assay + DYRK3 overexpression BMC biology Medium 34789250
2010 Drosophila Med15, a component of the Mediator complex, is required for transcription of decapentaplegic (Dpp) target genes during wing development; loss-of-function clones show defective wing patterning and reduced Dpp target gene expression. Genetic mosaic screen + loss-of-function clonal analysis in Drosophila wing Genetics Medium 20233856
2024 MED15 acts as a coactivator of SREBP transcription factors by directly interacting with SREBP1 and SREBP2, promoting SREBP-dependent lipid biosynthesis enzyme expression. MED15 also promotes SREBP1 and SREBP2 activation through the PLK1/AKT axis in clear cell renal cell carcinoma. HIF-2α transcriptionally activates MED15 by directly binding its promoter region. Co-immunoprecipitation + ChIP + siRNA knockdown + overexpression assays + reporter assays Cell death discovery Medium 38649345
2024 Mouse Med15 binds β-cell transcription factors Nkx6-1 and NeuroD1 as shown by co-immunoprecipitation and ChIP-seq; knockout of Med15 in mouse β-cells causes defects in β-cell maturation without affecting β-cell mass or insulin expression. Human embryonic stem cell-derived β-like cells engineered to overexpress MED15 show increased maturation markers. ChIP-seq + co-immunoprecipitation + conditional knockout mouse + human ESC overexpression model Nature communications High 39379383
2024 Med15 can select genomic target sites independent of promoter-bound transcription factors; it shows inherent preference for 'fuzzy-nucleosome' promoter architecture. Direct DBD-Med15 fusions shift localization toward fuzzy-nucleosome promoters including sites lacking endogenous Mediator, suggesting Med15 actively contributes to target site selection. ChIP-seq in budding yeast with DBD-AD fusion proteins + direct DBD-Med15 fusions + transcriptional assays Nucleic acids research Medium 39187372
2024 Drosophila Moesin directly binds the Med15 subunit of the Mediator complex in the nucleus. Both Moesin and Med15 bind heat shock factor (Hsf), and Moesin's presence at regulatory regions of the Hsp70Ab heat shock gene is Med15-dependent. Moesin, Med15, Hsf, and monomeric actin form a nuclear complex required for proper Hsp gene expression. The direct interaction between human orthologs of Drosophila Moesin and Med15 was confirmed. Co-immunoprecipitation + ChIP + RNAi knockdown + direct binding assays (Drosophila and human orthologs) Open biology Medium 39353569
2025 TGF-β selectively induces CDK1-mediated phosphorylation of MED15 at T603, which controls SASP gene expression and cellular senescence. Unphosphorylated MED15 is bound by forkhead box protein A1 (FOXA1) to suppress SASP gene expression; phosphorylation at T603 prevents FOXA1 binding, releasing SASP gene repression. Knock-in of the dephosphorylated T603A mutant in aging mice attenuates SASP and improves cognitive function. Phospho-mutagenesis (T603A/T603D) + co-immunoprecipitation + in vivo knock-in mouse model + behavioral assays + gene expression analysis Cell discovery High 40825935
2025 MED15 interacts with YAP1 and stabilizes it by attenuating TRIM11-mediated ubiquitination of YAP1, promoting EMT and cell migration in bladder cancer. Under sorbitol-induced stress, MED15 forms stress-inducible protein condensates with increased colocalization with YAP1. Co-immunoprecipitation + ubiquitination assay + siRNA knockdown + migration assays + condensate imaging FASEB journal Medium 41685983
2025 MDT-15/MED15 (C. elegans ortholog) and downstream fatty acid desaturases FAT-6 and FAT-7 are required for activation of the ESRE mitochondrial surveillance pathway; supplementation with polyunsaturated fatty acids downstream of FAT-6/FAT-7 rescues ESRE activation in mdt-15 knockdowns. Box C/D snoRNPs are required for upregulation of fatty acid metabolism under ESRE-activating conditions and act upstream of MDT-15 in this pathway. RNAi knockdown + ESRE reporter assays + fatty acid supplementation rescue + infection survival assays in C. elegans bioRxivpreprint Low 40501983
2024 ATXN1 amino acids 99-163 and MED15 amino acids 548-665 are critical for the ATXN1-MED15 protein-protein interaction, and MED15 significantly enhances aggregation of polyQ-expanded ATXN1. A small molecule inhibitor of this interaction (Chembridge ID: 5755483) inhibits both the ATXN1-MED15 interaction and dimerization of polyQ-expanded ATXN1. Computational structure prediction + experimental domain mapping + small molecule inhibitor assay + aggregation assays bioRxivpreprint Low bio_10.1101_2025.03.17.643445
2024 MED15 is specifically enriched (relative to other Mediator subunits) in the HTT interactome in the tail domain of Mediator; HTT modulates the subcellular localization and assembly of the Mediator complex as shown in HD and KO models. Multi-epitope immunocapture + mass spectrometry + subcellular fractionation in mouse and fly models bioRxivpreprint Low bio_10.1101_2024.09.07.611843
2024 Med15 polyglutamine (polyQ) tract composition and length modulate activator-binding domain (ABD) activity and transcription factor interactions; the Q1 tract is required for robust Med15 activity and its length modulates transcriptional activation by Msn2 by affecting Msn2-Med15 interaction strength. Intramolecular interactions between distant glutamine tracts and Med15 phosphorylation affect KIX domain activities. Phenotypic assays + gene expression analysis + transcription factor interaction assays (yeast) + phase separation assays Molecular and cellular biology Medium 39717019

Source papers

Stage 0 corpus · 64 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1991 Cooperative effect of antisense-Rb and antisense-p53 oligomers on the extension of life span in human diploid fibroblasts, TIG-1. Biochemical and biophysical research communications 246 1909121
2011 The acidic transcription activator Gcn4 binds the mediator subunit Gal11/Med15 using a simple protein interface forming a fuzzy complex. Molecular cell 166 22195967
2008 Mediator subunit Gal11p/MED15 is required for fatty acid-dependent gene activation by yeast transcription factor Oaf1p. The Journal of biological chemistry 82 19056732
2013 Mediator recruitment to heat shock genes requires dual Hsf1 activation domains and mediator tail subunits Med15 and Med16. The Journal of biological chemistry 65 23447536
2019 Promoter Hypermethylation of Tumor-Suppressor Genes p16INK4a,RASSF1A,TIMP3, and PCQAP/MED15 in Salivary DNA as a Quadruple Biomarker Panel for Early Detection of Oral and Oropharyngeal Cancers. Biomolecules 61 31013839
2009 Activator Gcn4 employs multiple segments of Med15/Gal11, including the KIX domain, to recruit mediator to target genes in vivo. The Journal of biological chemistry 60 19940160
2016 The Mediator Complex MED15 Subunit Mediates Activation of Downstream Lipid-Related Genes by the WRINKLED1 Transcription Factor. Plant physiology 56 27246098
1992 Interleukin-1 up-regulates transcription of its own receptor in a human fibroblast cell line TIG-1: role of endogenous PGE2 and cAMP. European journal of immunology 52 1315688
2021 Mediator subunit Med15 dictates the conserved "fuzzy" binding mechanism of yeast transcription activators Gal4 and Gcn4. Nature communications 44 33850123
2014 The evolutionarily conserved mediator subunit MDT-15/MED15 links protective innate immune responses and xenobiotic detoxification. PLoS pathogens 41 24875643
2014 DNA Methylation at the Novel CpG Sites in the Promoter of MED15/PCQAP Gene as a Biomarker for Head and Neck Cancers. Biomarker insights 41 25057238
2016 The Mediator Complex Subunits MED14, MED15, and MED16 Are Involved in Defense Signaling Crosstalk in Arabidopsis. Frontiers in plant science 38 28066497
2006 TRIM11 binds to and destabilizes a key component of the activator-mediated cofactor complex (ARC105) through the ubiquitin-proteasome system. FEBS letters 32 16904669
1991 A new human male diploid cell strain, TIG-7: its age-related changes and comparison with a matched female TIG-1 cell strain. Experimental gerontology 30 1800129
2013 MED15, encoding a subunit of the mediator complex, is overexpressed at high frequency in castration-resistant prostate cancer. International journal of cancer 28 24374838
1984 Loss of responsiveness in senescent human TIG-1 cells to the DNA synthesis-inducing effect of various growth factors. Mechanisms of ageing and development 28 6333569
2019 Mediator subunit MDT-15/MED15 and Nuclear Receptor HIZR-1/HNF4 cooperate to regulate toxic metal stress responses in Caenorhabditis elegans. PLoS genetics 24 31815936
2017 MED15 overexpression in prostate cancer arises during androgen deprivation therapy via PI3K/mTOR signaling. Oncotarget 23 27974704
1994 Interleukin-1 down-regulates type I interleukin 1 receptor mRNA expression in a human fibroblast cell line TIG-1 in the absence of prostaglandin E2 synthesis. Lymphokine and cytokine research 23 7948430
2015 Clinical and molecular implications of MED15 in head and neck squamous cell carcinoma. The American journal of pathology 21 25791637
2019 Med15: Glutamine-Rich Mediator Subunit with Potential for Plasticity. Trends in biochemical sciences 19 31036407
2024 MED15 is upregulated by HIF-2α and promotes proliferation and metastasis in clear cell renal cell carcinoma via activation of SREBP-dependent fatty acid synthesis. Cell death discovery 18 38649345
2021 Formation of nuclear condensates by the Mediator complex subunit Med15 in mammalian cells. BMC biology 18 34789250
2010 Identification of genes affecting wing patterning through a loss-of-function mutagenesis screen and characterization of med15 function during wing development. Genetics 18 20233856
2019 A Rare Partner of TFE3 in the Xp11 Translocation Renal Cell Carcinoma: Clinicopathological Analyses and Detection of MED15-TFE3 Fusion. BioMed research international 16 31828108
2003 Association study between CAG trinucleotide repeats in the PCQAP gene (PC2 glutamine/Q-rich-associated protein) and schizophrenia. American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics 16 12497610
2023 MED15::TFE3 Renal Cell Carcinomas: Report of Two New Cases and Review of the Literature Confirming Nearly Universal Multilocular Cystic Morphology. International journal of surgical pathology 15 36591911
2024 DELLA proteins recruit the Mediator complex subunit MED15 to coactivate transcription in land plants. Proceedings of the National Academy of Sciences of the United States of America 14 38696472
2021 MED15 prion-like domain forms a coiled-coil responsible for its amyloid conversion and propagation. Communications biology 14 33772081
2020 The Polymorphic PolyQ Tail Protein of the Mediator Complex, Med15, Regulates the Variable Response to Diverse Stresses. International journal of molecular sciences 14 32164312
2024 MED15::ATF1-Rearranged Tumor: A Novel Cutaneous Tumor With Melanocytic Differentiation. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 13 38278485
2015 Differential expression of Mediator complex subunit MED15 in testicular germ cell tumors. Diagnostic pathology 13 26377566
2013 Functional studies of the yeast med5, med15 and med16 mediator tail subunits. PloS one 13 23991176
1988 Changes in negative surface charge of human diploid fibroblasts, TIG-1, during in vitro aging. Mechanisms of ageing and development 13 3361969
1986 Events blocked in prereplicative phase in senescent human diploid cells, TIG-1, following serum stimulation. Mechanisms of ageing and development 13 2434812
2023 Cystic MED15::TFE3 translocation renal cell carcinoma: histologic mimicker of multilocular cystic renal neoplasm of low malignant potential with review of the literature. Human pathology 12 36997032
1995 Type I and type II interferons upregulate functional type I interleukin-1 receptor in a human fibroblast cell line TIG-1. Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research 12 8746788
1982 Ganglioside changes during cell aging in human diploid fibroblast TIG-1. Experimental gerontology 12 7160447
2018 The Mediator complex subunit MED15, a promoter of tumour progression and metastatic spread in renal cell carcinoma. Cancer biomarkers : section A of Disease markers 11 29400661
2011 Establishment of human induced pluripotent stem cell lines from normal fibroblast TIG-1. Human cell 11 21562774
2004 An association study of PCQAP polymorphisms and schizophrenia. Psychiatric genetics 10 15318033
2024 Revisiting the model for coactivator recruitment: Med15 can select its target sites independent of promoter-bound transcription factors. Nucleic acids research 9 39187372
2014 Human mediator subunit MED15 promotes transcriptional activation. Drug discoveries & therapeutics 9 25382556
2000 A novel glutamine-rich putative transcriptional adaptor protein (TIG-1), preferentially expressed in placental and bone-marrow tissues. Gene 8 11024300
2024 Novel MED15::ATF1 fusion in a pediatric melanoma with spitzoid features and aggressive presentation. Genes, chromosomes & cancer 6 38459940
2018 The knockdown of the Mediator complex subunit MED15 restrains urothelial bladder cancer cells' malignancy. Oncology letters 6 30127891
2012 Establishment of ultra long-lived cell lines by transfection of TERT into normal human fibroblast TIG-1 and their characterization. Cell biology international 6 22273270
1986 Failure in S6 protein phosphorylation by serum stimulation of senescent human diploid fibroblasts, TIG-1. Mechanisms of ageing and development 5 3821186
1981 Effects of in vitro aging and cell growth on the viability and recovery of human diploid fibroblasts, TIG-1, after freezing and thawing. Mechanisms of ageing and development 5 7266075
2025 The mediator subunit complex protein MED15 promotes lipid deposition and cancer progression during hypoxia. The Journal of biological chemistry 4 39947475
2024 MED15::TFE3 fusion renal cell carcinoma with extensive cystic change: A clinicopathologic and molecular genetic study of 2 cases, with an emphasis on differential diagnosis. American journal of clinical pathology 4 38387043
2024 Transcriptional coactivator MED15 is required for beta cell maturation. Nature communications 4 39379383
2024 The Role of Med15 Sequence Features in Transcription Factor Interactions. Molecular and cellular biology 4 39717019
2021 Possible Role for Allelic Variation in Yeast MED15 in Ecological Adaptation. Frontiers in microbiology 4 34733258
2012 Genetic and physical interactions between Tel2 and the Med15 Mediator subunit in Saccharomyces cerevisiae. PloS one 3 22291956
2024 Moesin contributes to heat shock gene response through direct binding to the Med15 subunit of the Mediator complex in the nucleus. Open biology 2 39353569
2019 PFG acted as an inducer of premature senescence in TIG-1 normal diploid fibroblast and an inhibitor of mitosis in the HeLa cells. Bioscience, biotechnology, and biochemistry 2 30836860
2025 [MED15-TFE3 renal cell carcinoma: a clinicopathological and molecular analysis]. Zhonghua bing li xue za zhi = Chinese journal of pathology 1 39762166
2025 A phosphorylation switch in the Mediator MED15 controls cellular senescence and cognitive decline. Cell discovery 1 40825935
2023 Mediator Subunit Med15 Regulates Cell Morphology and Mating in Candida lusitaniae. Journal of fungi (Basel, Switzerland) 1 36983501
2022 Clinical and Histopathological Factors Associated with the Tumoral Expression of TGF-β1, MED15, CD16, and CD57 in Oral Squamous Cell Carcinoma. Advances in preventive medicine 1 36340330
2026 Transcriptomic shift in ethanol and amino acid metabolic genes regulated by Med15 during alcoholic fermentation. bioRxiv : the preprint server for biology 0 41542482
2026 Role of MED15 in Enhancing EMT and Metastasis in Bladder Cancer Through YAP1 Stabilization. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 0 41685983
2025 Box C/D snoRNPs and MDT-15/MED15 regulate mitochondrial surveillance via fatty acid metabolism. bioRxiv : the preprint server for biology 0 40501983