Affinage

MED15

Mediator of RNA polymerase II transcription subunit 15 · UniProt Q96RN5

Length
788 aa
Mass
86.8 kDa
Annotated
2026-06-10
64 papers in source corpus 26 papers cited in narrative 26 extracted findings
Cross-family judge vs UniProt: tie faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

MED15 is a tail-module subunit of the Mediator co-activator complex that bridges sequence-specific transcription factors to the RNA Polymerase II machinery and thereby controls inducible gene-expression programs across eukaryotes (PMID:23447536, PMID:11024300). Its defining biochemical feature is a set of activator-binding domains, including a KIX domain, that engage intrinsically disordered acidic activation domains through a dynamic 'fuzzy' interface: the activation domains of Gcn4 and Gal4 bind nearly identically using transient hydrophobic contacts rather than a single fixed conformation, and the same domains adopt structured complexes only when the partner itself is structured (PMID:22195967, PMID:33850123). Through these adaptable surfaces MED15 integrates diverse upstream regulators — Gcn4 and Hsf1 at heat-shock and amino-acid genes, the lipid-sensing factors Oaf1p and SREBP1/2, the nuclear receptor HIZR-1, and tissue factors Nkx6-1 and NeuroD1 — to drive fatty-acid/lipid-metabolism, stress, metal-response, and cell-maturation programs (PMID:19056732, PMID:23447536, PMID:31815936, PMID:39379383, PMID:38649345). In yeast the tail module performs essential functions, with Med15 loss down-regulating Ace2 targets and arresting cells in G1, and Med15 contributes intrinsic promoter selectivity toward fuzzy-nucleosome regulatory regions independent of activator tethering (PMID:23991176, PMID:39187372). MED15 is regulated post-translationally by TRIM11-mediated ubiquitin-proteasome degradation and by CDK1 phosphorylation at T603, which licenses SASP gene expression and cellular senescence while unphosphorylated MED15 is bound by FOXA1 to suppress this program (PMID:16904669, PMID:40825935). Its glutamine-rich intrinsically disordered region together with a downstream hydrophobic motif drives formation of liquid-like nuclear condensates and, in a prion-like coiled-coil-dependent manner, can recruit endogenous MED15 into amyloid inclusions (PMID:34789250, PMID:33772081).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 2000 Low

    Establishing that the human protein is a nuclear, DNA-tethered transcriptional regulator placed MED15 within a chromatin-directed co-activator complex.

    Evidence GAL4-fusion reporter assays, NLS identification and cDNA screening identifying the ARC complex component (TIG-1/ARC105)

    PMID:11024300

    Open questions at the time
    • Single tethered reporter assay without endogenous functional validation
    • Native complex context and direct activator partners not defined
  2. 2008 High

    Linking the Gal11/MED15 KIX domain to fatty-acid-dependent activation by Oaf1p connected the subunit to lipid-metabolism gene regulation and showed shared use of the KIX surface by distinct activators.

    Evidence Genetic deletion, NMR spectroscopy and fatty-acid growth assays in yeast

    PMID:19056732

    Open questions at the time
    • Whether the same mechanism operates at endogenous metabolic genes in metazoans not addressed here
  3. 2009 High

    Mapping Gcn4 recruitment to multiple N-terminal Gal11 segments including KIX and a B-box established that activator-Mediator recruitment is additive and multivalent in vivo.

    Evidence In vitro binding, NMR chemical-shift analysis, site-directed mutagenesis and in vivo ChIP at ARG1

    PMID:19940160

    Open questions at the time
    • Relative contribution of each segment to Pol II output not fully quantified
    • Structural basis of B-box engagement not resolved
  4. 2011 High

    Defining the Gcn4-Gal11 interface as a 'fuzzy', dynamic, hydrophobic complex answered how a single Mediator surface accommodates diverse acidic activators without a fixed structure.

    Evidence NMR structural analysis with mutagenesis and functional validation in yeast

    PMID:22195967

    Open questions at the time
    • Generality across non-acidic activators untested at this point
    • How fuzzy binding translates to recruitment kinetics unresolved
  5. 2013 Medium

    Showing cooperative recruitment of holo-Mediator to HSP promoters and essential tail-module functions defined MED15 as a critical, partly module-autonomous recruitment hub.

    Evidence ChIP and genetic deletion/truncation, plus N-Degron depletion with transcriptome profiling and cell-cycle analysis in S. cerevisiae

    PMID:23447536 PMID:23991176

    Open questions at the time
    • Molecular basis of tail-module essentiality independent of Head/Middle modules unknown
    • Direct vs indirect effects on Ace2 targets not dissected
  6. 2014 Medium

    Loss-of-function studies extended MED15 function to mammalian SREBP/VP16 and p53/p21 activation and to xenobiotic detoxification and innate immunity in C. elegans, establishing conserved roles in metabolic and stress-response transcription.

    Evidence siRNA knockdown/rescue, co-localization and ChIP in human cells; RNAi screen and infection survival assays in C. elegans

    PMID:24875643 PMID:25382556

    Open questions at the time
    • Whether MED15 acts directly at these promoters or via complex integrity unclear
    • Mechanism connecting detoxification and immunity gene programs not defined
  7. 2013 Medium

    Identifying MED15 as a TGF-β-responsive regulator of p-SMAD3 nuclear shuttling and proliferation tied the subunit to oncogenic signaling in prostate cancer.

    Evidence siRNA/shRNA knockdown, proliferation assays, IHC and Western blot for p-SMAD3

    PMID:24374838

    Open questions at the time
    • Direct MED15-SMAD3 interaction not demonstrated
    • Whether effect is Mediator-dependent unresolved
  8. 2019 High

    Demonstrating metal-stimulated MED15/MDT-15 cooperation with HIZR-1 and conserved binding at metallothionein/zinc-transporter genes generalized the activator-bridging role to metal-responsive transcription across species.

    Evidence Yeast two-hybrid, qRT-PCR, reporter and gain/loss-of-function genetics in C. elegans plus mammalian ChIP and human cell knockdown

    PMID:31815936

    Open questions at the time
    • Structural basis of metal-enhanced MDT-15/HIZR-1 binding not resolved
    • Whether mammalian orthologs use the same nuclear receptor interface unclear
  9. 2021 High

    Showing that Gal4 and Gcn4 use the same fuzzy mechanism while the structured partner dictates interaction type clarified that Mediator surfaces, not the activators alone, define binding mode.

    Evidence NMR chemical-shift perturbation and binding assays with multiple activation domains and the Gal80 repressor

    PMID:33850123

    Open questions at the time
    • Quantitative link between fuzzy affinity and transcriptional output not established
  10. 2021 Medium

    Defining a glutamine-rich IDR plus hydrophobic motif as drivers of liquid-like nuclear condensates, and a coiled-coil PrLD that templates prion-like amyloid recruitment, revealed a phase-separation/aggregation axis governing MED15 behavior.

    Evidence Live-cell imaging, FRAP, optodroplet and domain-deletion assays with DYRK3 overexpression; biophysical dimerization and amyloid assays with coiled-coil mutagenesis

    PMID:33772081 PMID:34789250

    Open questions at the time
    • Functional role of condensates in active transcription not established
    • Physiological triggers of prion-like conversion unknown
  11. 2024 High

    Reciprocal binding to Nkx6-1 and NeuroD1 and conditional knockout phenotypes established a tissue-specific MED15 requirement for pancreatic β-cell maturation.

    Evidence ChIP-seq, co-IP, β-cell-specific conditional knockout mouse and human ESC-derived β-like cell overexpression

    PMID:39379383

    Open questions at the time
    • Which maturation genes depend directly on MED15 versus secondary effects not fully resolved
    • Mechanism distinguishing maturation from mass/insulin output unknown
  12. 2024 Medium

    Placing MED15 in SREBP and HIF lipid-metabolic circuits, including a HIF feedback loop upstream of CPT1A and SREBP activation via PLK1/AKT, defined MED15 as a node coupling hypoxia and lipid biosynthesis in cancer.

    Evidence Co-IP, ChIP, siRNA knockdown and overexpression rescue in ccRCC; zebrafish med15 knockout with reporter and lipid-droplet assays and xenografts

    PMID:38649345 PMID:39947475

    Open questions at the time
    • Direct versus indirect contribution to SREBP and HIF target genes not fully separated
    • Stoichiometry and physical basis of SREBP binding undefined
  13. 2024 Medium

    Demonstrating intrinsic promoter selectivity toward fuzzy-nucleosome regions and a nuclear Moesin/actin/Hsf complex showed MED15 actively shapes target selection beyond passive activator recruitment.

    Evidence ChIP-seq with DBD-AD and DBD-Med15 fusions in yeast; co-IP, ChIP and RNAi in Drosophila with human ortholog validation

    PMID:39187372 PMID:39353569

    Open questions at the time
    • Chromatin features driving intrinsic preference not mechanistically defined
    • Role of nuclear actin in the Moesin-Med15-Hsf complex unresolved
  14. 2025 Medium

    Identifying TGF-β/CDK1-driven phosphorylation at T603 as a switch controlled by FOXA1 binding established a post-translational mechanism linking MED15 to SASP gene expression, senescence and cognitive aging.

    Evidence T603A/T603D mutagenesis, co-IP, gene expression analysis and a mouse knock-in with behavioral assays

    PMID:40825935

    Open questions at the time
    • How phosphorylation alters MED15 partner choice or condensate behavior unknown
    • Direct CDK1-MED15 modification in vivo not structurally defined
  15. 2024 Medium

    Reporting MED15 stabilization of YAP1 by attenuating TRIM11-mediated ubiquitination and stress-inducible MED15/YAP1 condensates connected MED15 protein turnover, EMT and condensate biology in bladder cancer.

    Evidence Co-IP, ubiquitination assays, loss/gain-of-function, migration assays and condensate imaging

    PMID:41685983

    Open questions at the time
    • Mechanism by which MED15 blocks TRIM11 on YAP1 unresolved
    • Relationship between MED15 and YAP1 within Mediator not defined

Open questions

Synthesis pass · forward-looking unresolved questions
  • How MED15's fuzzy activator binding, intrinsic promoter selectivity, condensate/prion-like properties and post-translational control (phosphorylation, TRIM11 ubiquitination) are integrated into a single regulatory logic at native genes remains unresolved.
  • No unified structural model connecting condensate state to activator selection
  • Mechanism coupling T603 phosphorylation and TRIM11 turnover not established
  • Whether disease-associated polyQ interactions (HTT, ATXN1) reflect physiological MED15 function is unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 3 GO:0098772 molecular function regulator activity 3 GO:0140110 transcription regulator activity 3 GO:0003677 DNA binding 2
Localization
GO:0005634 nucleus 3 GO:0005654 nucleoplasm 2
Pathway
R-HSA-1430728 Metabolism 3 R-HSA-162582 Signal Transduction 3 R-HSA-74160 Gene expression (Transcription) 3 R-HSA-8953897 Cellular responses to stimuli 3
Complex memberships
Mediator complex (tail module)

Evidence

Reading pass · 26 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2011 The acidic activation domain (AD) of transcription activator Gcn4 binds the Mediator subunit Gal11/Med15 activator-binding domain 1 (a four-helix fold with a shallow hydrophobic cleft) through a dynamic, 'fuzzy' protein interface involving only hydrophobic interactions; eight residues of Gcn4 adopt a helical conformation allowing three aromatic/aliphatic residues to insert into the Gal11 cleft, and the complex cannot be described by a single conformation. NMR structural analysis combined with mutagenesis and functional studies in yeast Molecular cell High 22195967
2009 Gcn4 recruits Mediator to the ARG1 promoter in vivo through additive interactions with three distinct N-terminal segments of Gal11/Med15, including the KIX domain and a B-box motif; NMR chemical shift analysis identified the Gcn4 binding site on the Gal11 KIX surface, and mutagenesis of B-box established it as a critical determinant of Mediator recruitment. In vitro binding assays, ChIP (Mediator recruitment in vivo), NMR chemical shift analysis, site-directed mutagenesis The Journal of biological chemistry High 19940160
2008 The yeast Mediator subunit Gal11p/MED15 and its KIX domain are required for fatty acid-dependent transcriptional activation by the PPARα analog Oaf1p; NMR spectroscopy revealed that the Oaf1p activation domain interacts with the Gal11p/MED15 KIX domain in a manner similar to the xenobiotic receptor Pdr1p. Genetic deletion analysis, NMR spectroscopy, fatty acid growth assays The Journal of biological chemistry High 19056732
2013 Med15 (Tail module subunit) and Med16 cooperate to recruit holo-Mediator to HSP gene promoters in yeast in response to heat shock; Hsf1 recruits Mediator via dual N- and C-terminal activation domains through cooperative interactions with the Tail module, and loss of both Med15 and Med16 abolishes Mediator occupancy and substantially reduces RNA Pol II recruitment. ChIP (chromatin immunoprecipitation), genetic deletion/truncation analysis in Saccharomyces cerevisiae The Journal of biological chemistry High 23447536
2021 Gal4 and Gcn4, two intrinsically disordered acidic activation domains of different sequence, interact nearly identically with Med15 via a 'fuzzy' protein interface; the two hydrophobic regions of the Gal4 AD each independently bind Med15 using this fuzzy mechanism, while the same Gal4 AD region binds Gal80 repressor via a distinct structured complex, indicating the structured binding partner dictates the interaction type. NMR chemical shift perturbation analysis, binding assays Nature communications High 33850123
2006 TRIM11 binds to MED15 (ARC105) and promotes its degradation through the ubiquitin-proteasome pathway; co-expression of TRIM11 increases ARC105 ubiquitination and degradation (blocked by proteasome inhibitor), and TRIM11 suppresses ARC105-mediated transcriptional activation induced by TGF-β in a reporter assay. Co-immunoprecipitation, ubiquitination assay, proteasome inhibitor treatment, transcriptional reporter assay FEBS letters Medium 16904669
2013 In yeast, loss of Med15 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 mutants indicates the Tail module performs essential functions even when separated from Head and Middle modules. Temperature-sensitive N-Degron mutants, global gene expression profiling, cell cycle analysis PloS one Medium 23991176
2014 Human MED15 co-localizes with general transcription factors TFIIE and TFIIH in the nucleus; MED15 knockdown reduces VP16- and SREBP1a-driven transcriptional activation, rescued by wild-type MED15 re-expression; MED15 localizes to both the p53 binding site and the p21 promoter region upon Nutlin-3 induction. siRNA knockdown, immunostaining/co-localization, transcriptional reporter assay, ChIP Drug discoveries & therapeutics Medium 25382556
2013 MED15 knockdown in prostate cancer cells reduces TGF-β-enhanced proliferation, affects phosphorylation and nuclear shuttling of p-SMAD3, and decreases both androgen-dependent and androgen-independent proliferation; TGF-β signaling activation leads to increased MED15 expression in PCa cells. siRNA/shRNA knockdown, proliferation assays, immunohistochemistry, Western blot for p-SMAD3 International journal of cancer Medium 24374838
2014 C. elegans MDT-15/MED15 is required for xenobiotic-induced expression of PMK-1 p38 MAP kinase-dependent immune genes and for protection from Pseudomonas aeruginosa infection; MDT-15 also controls induction of detoxification genes and protects from phenazine toxins, linking xenobiotic detoxification and innate immunity. RNAi screen (1,420 genes), gene expression analysis, infection survival assays in C. elegans PLoS pathogens Medium 24875643
2019 C. elegans MDT-15 physically and functionally cooperates with the nuclear hormone receptor HIZR-1 to promote induction of zinc and cadmium responsive genes; the physical interaction between MDT-15 and HIZR-1 is enhanced by zinc or cadmium in yeast two-hybrid assays; mdt-15 and hizr-1 mutants show defective zinc storage in the gut and hypersensitivity to zinc-induced reductions in egg-laying; mammalian MED15 orthologs bind genomic regulatory regions of metallothionein and zinc transporter genes in a cadmium/zinc-stimulated fashion, and human MED15 is required to induce a metallothionein gene in lung adenocarcinoma cells. Yeast two-hybrid, qRT-PCR, reporter analysis, gain/loss-of-function genetics, ChIP (mammalian cells), siRNA knockdown in human cells PLoS genetics High 31815936
2021 Human MED15 forms nuclear condensates (foci) that are sensitive to 1,6-hexanediol and show rapid FRAP recovery; condensate formation requires both the glutamine-rich intrinsically disordered region (IDR) and a short downstream hydrophobic motif; DYRK3 kinase overexpression disrupts Med15 foci; the MED15 prion-like domain drives phase separation and can kidnap endogenous full-length MED15 into cytoplasmic/perinuclear inclusions in a prion-like manner. Live cell imaging, immunostaining, FRAP, optodroplet assay, domain deletion analysis, DYRK3 overexpression BMC biology Medium 34789250
2021 The human MED15 prion-like domain (PrLD) forms homodimers sustained by coiled-coil (CC) interactions; CC disruption (chemical or genetic) abolishes amyloid aggregation; the CC fold mediates transition to a β-sheet amyloid state; a GFP domain adjacent to the PrLD retains its structure in the amyloid state; MED15-PrLD expression in human cells promotes prion-like recruitment of endogenous full-length MED15 to cytoplasmic inclusions. Biophysical dimerization assays, amyloid aggregation assays, coiled-coil mutagenesis, fluorescence microscopy in human cells Communications biology Medium 33772081
2024 Mouse Med15 binds pancreatic β-cell transcription factors Nkx6-1 and NeuroD1 (by co-immunoprecipitation and ChIP-seq) to regulate key β-cell maturation genes; β-cell-specific Med15 knockout 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 marker expression. ChIP-seq, co-immunoprecipitation, conditional knockout mouse, human ESC differentiation system Nature communications High 39379383
2024 MED15 directly interacts with SREBPs (SREBP1 and SREBP2) to promote SREBP-dependent lipid biosynthesis enzyme expression in clear cell renal cell carcinoma; MED15 also promotes SREBP1/2 activation through the PLK1/AKT axis; HIF-2α promotes MED15 transcriptional activation by directly binding the MED15 promoter. Co-immunoprecipitation, promoter binding assay (ChIP), siRNA knockdown, overexpression rescue experiments Cell death discovery Medium 38649345
2024 Med15 in budding yeast can select its chromosomal binding sites (characterized by fuzzy-nucleosome architecture) independent of promoter-bound transcription factors; direct DBD-Med15 fusions shift DBD localization towards fuzzy-nucleosome promoters, indicating Med15 has inherent promoter preference and actively contributes to target gene selection. ChIP-seq with DBD-AD fusions, direct DBD-Med15 fusions, genome-wide localization in budding yeast Nucleic acids research Medium 39187372
2025 TGF-β selectively induces CDK1-mediated phosphorylation of MED15 at T603, which controls SASP gene expression and cellular senescence; the T603A (dephosphorylated) mutant inhibits SASP and cell senescence, while T603D (phosphomimetic) promotes them; forkhead box protein A1 (FOXA1) preferentially binds unphosphorylated MED15-T603 to suppress SASP gene expression; aging mice with T603A mutation show improved learning and memory through SASP attenuation. Site-directed mutagenesis (T603A/T603D), Co-immunoprecipitation, gene expression analysis, mouse knock-in model, behavioral assays Cell discovery Medium 40825935
2024 Drosophila Moesin directly interacts with the Med15 subunit of the Mediator complex in the nucleus; Moesin's presence at regulatory regions of the Hsp70Ab heat shock gene is Med15-dependent; both Moesin and Med15 bind heat shock factor (Hsf), and together with monomeric actin form a nuclear complex required for proper Hsp gene expression; direct interaction between the human orthologs of Moesin and Med15 was confirmed. Co-immunoprecipitation, ChIP, RNAi knockdown, gene expression analysis in Drosophila and human cells Open biology Medium 39353569
2025 MED15 acts as a HIF target gene that participates in a positive feedback loop promoting HIF transcriptional activity; MED15 acts upstream of CPT1A (carnitine palmitoyltransferase 1A, a key fatty acid oxidation enzyme) to promote HIF-mediated lipid droplet accumulation; zebrafish med15 deficiency decreases HIF activity and impairs hypoxic stress tolerance. siRNA knockdown, zebrafish med15 knockout, reporter assays, lipid droplet quantification, tumor xenograft The Journal of biological chemistry Medium 39947475
2024 MED15 interacts with YAP1 and stabilizes it by attenuating TRIM11-mediated ubiquitination in bladder cancer cells; MED15 promotes EMT and cell migration in a YAP1-dependent manner; under osmotic stress, MED15 forms stress-inducible protein condensates with increased YAP1 co-localization. Co-immunoprecipitation, ubiquitination assay, loss- and gain-of-function (siRNA/overexpression), migration assays, condensate imaging FASEB journal Medium 41685983
2010 Drosophila Med15 is required for transcription of Decapentaplegic (Dpp/BMP) target genes during wing development; loss-of-function clones in mosaic wings establish Med15 as a component needed for proper wing patterning and epithelial gene regulation. Loss-of-function genetic screen, mosaic clone analysis, gene expression analysis in Drosophila Genetics Medium 20233856
2024 Med15 KIX domain length and polyglutamine (polyQ) tract composition modulate interactions with specific transcription factors (including Msn2); reduced Msn2:Med15 interaction strength correlates with reduced Msn2-dependent transcriptional activation; intramolecular interactions between distant glutamine tracts and MED15 phosphorylation affect KIX domain activities; individual ABDs and adjacent polyQ tracts each contribute to Med15 activity in a context-dependent manner. Truncation/deletion/synthetic allele analysis, phenotypic assays, gene expression analysis, transcription factor interaction assays, phase separation assays in yeast Molecular and cellular biology Medium 39717019
2012 Med15/Gal11 physically associates with Tel2 in yeast when transiently overproduced; overexpression of MED15/GAL11 partially suppresses tel2 temperature-sensitive mutant phenotypes including short telomeres and defective EST2 (telomerase catalytic subunit) transcription. Co-immunoprecipitation, genetic suppressor analysis, gene expression analysis PloS one Low 22291956
2000 The human MED15 (TIG-1/ARC105) protein contains a bipartite nuclear localization signal, localizes to the nucleus, and when tethered to DNA via a GAL4 fusion demonstrates transcriptional regulatory activity in co-transfection assays; the protein was identified as a component of the ARC chromatin-directed transcriptional co-activator complex. Co-transfection reporter assay, Western blot, nuclear localization signal identification, cDNA library screening Gene Low 11024300
2024 Huntingtin (HTT) associates with MED15 preferentially in the Mediator tail domain, and HTT modulates the subcellular localization and assembly of the Mediator complex in HD and KO models. Multi-epitope immunocapture/co-immunoprecipitation, subcellular fractionation, mass spectrometry, Drosophila genetic modifier assays bioRxiv (preprint)preprint Low bio_10.1101_2024.09.07.611843
2025 ATXN1 amino acids 99-163 and MED15 amino acids 548-665 are critical for their protein-protein interaction; MED15 significantly enhances aggregation of polyQ-expanded ATXN1; a small molecule (Chembridge ID: 5755483) targeting the ATXN1 aa99-163 domain inhibits both the ATXN1-MED15 interaction and dimerization of polyQ-expanded ATXN1. Computational structure prediction, co-immunoprecipitation/interaction assays with domain mutants, aggregation assays, virtual screening and chemical compound validation bioRxiv (preprint)preprint Low bio_10.1101_2025.03.17.643445

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 167 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 66 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 61 19940160
2016 The Mediator Complex MED15 Subunit Mediates Activation of Downstream Lipid-Related Genes by the WRINKLED1 Transcription Factor. Plant physiology 57 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 45 33850123
2014 The evolutionarily conserved mediator subunit MDT-15/MED15 links protective innate immune responses and xenobiotic detoxification. PLoS pathogens 42 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
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 26 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
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 19 36591911
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 17 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
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 15 38278485
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 15 38696472
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 14 36997032
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
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
2024 Revisiting the model for coactivator recruitment: Med15 can select its target sites independent of promoter-bound transcription factors. Nucleic acids research 12 39187372
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
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
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 5 38387043
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 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
2025 A phosphorylation switch in the Mediator MED15 controls cellular senescence and cognitive decline. Cell discovery 2 40825935
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
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
2026 Comprehensive analysis of six MED15::TFE3 renal cell carcinomas including two novel solid MED15::TFE3 renal cell carcinomas, highlighting their morphologic, immunohistochemical and molecular differences from their cystic counterparts. Virchows Archiv : an international journal of pathology 0 42113263
2025 Box C/D snoRNPs and MDT-15/MED15 regulate mitochondrial surveillance via fatty acid metabolism. bioRxiv : the preprint server for biology 0 40501983

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