Affinage

MED10

Mediator of RNA polymerase II transcription subunit 10 · UniProt Q9BTT4

Length
135 aa
Mass
15.7 kDa
Annotated
2026-06-10
37 papers in source corpus 18 papers cited in narrative 18 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 5/5 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

MED10 (NUT2) is an essential, conserved subunit of the Mediator coactivator complex that couples gene-specific regulatory signals to RNA polymerase II transcription (PMID:9812975, PMID:15175163). Within the seven-subunit Mediator middle module, MED10 occupies a structural hub: it flanks the Med7/Med21 heterodimer and bridges to the tail module by binding both Med7 and Med4, contacts mapped by reconstitution and biophysical analysis (PMID:20123732, PMID:23939621), with additional direct interaction with Med21 (PMID:16758199). Functionally, MED10 is required genome-wide for preinitiation complex assembly through a direct functional interaction with TFIIB (PMID:27688401), yet it also confers activator- and pathway-selective outputs rather than purely global control: in yeast it is specifically needed for Gcn4-mediated transcription of amino acid biosynthetic genes and for repression of a distinct gene set, distinguishing it from globally required subunits (PMID:9891034, PMID:11470794). In vertebrates this selectivity manifests as differential signal transduction, with zebrafish Med10 simultaneously restraining Wnt and promoting Nodal signaling during embryogenesis and acting downstream of Foxn4 and upstream of Tbx2b to drive heart valve formation (PMID:17208216, PMID:27343557). In mammalian cancers MED10 acts as an oncogenic driver: it promotes bladder and hepatocellular carcinoma proliferation, migration and invasion (PMID:35096564), activates RAF1 through a MEK/ERK/c-Myc axis (PMID:40917057), and drives PTEN ubiquitination-mediated degradation to confer cisplatin resistance (PMID:40183262).

Mechanistic history

Synthesis pass · year-by-year structured walk · 9 steps
  1. 1998 High

    Established MED10/NUT2 as a bona fide physical component of the RNA polymerase II Mediator holoenzyme, and as a nuclear, essential transcriptional regulator.

    Evidence Peptide sequencing, copurification and reciprocal co-IP with Pol II holoenzyme, plus genetic analysis with temperature-sensitive alleles and lacZ reporters in yeast

    PMID:9671481 PMID:9812975

    Open questions at the time
    • Did not resolve which Mediator submodule MED10 belongs to
    • Repressive versus activating role not mechanistically separated
  2. 1999 Medium

    Showed MED10 confers activator-specific transcriptional requirements rather than purely global ones, and is conserved as a human SMCC/Mediator component with dual repressive and activating capacity.

    Evidence Yeast Mediator subunit cloning with differential display/Northern analysis of activator mutants; biochemical purification of human SMCC with in vitro transcription assays

    PMID:10024883 PMID:9891034

    Open questions at the time
    • Molecular basis of activator selectivity unresolved
    • How a single subunit supports both repression and activation not defined
  3. 2001 Medium

    Defined MED10/Nut2 as a discrete module of the Rgr1 subcomplex specifically required for repression of a distinct gene group, refining its position within Mediator architecture.

    Evidence Biochemical subunit fractionation, genome-wide expression analysis, Northern analysis and GST pull-down in yeast

    PMID:11470794

    Open questions at the time
    • Direct repressor contacts of the Med10 module not identified
    • Mechanism linking module to specific repressed genes unknown
  4. 2006 Medium

    Mapped MED10 as a direct physical partner of Med21 within the middle module, establishing concrete intramodular contacts.

    Evidence Yeast two-hybrid and reciprocal co-IP of recombinant proteins from insect cells and E. coli

    PMID:16758199

    Open questions at the time
    • Functional consequence of the Med10-Med21 interface not tested in vivo
    • Single lab
  5. 2007 Low

    Placed MED10/Nut2 in functional antagonism with the NC2 repressor in basal transcription control.

    Evidence Genetic suppressor analysis with Nut2 level reduction and growth assays in yeast

    PMID:17339209

    Open questions at the time
    • Genetic suppression only, no direct biochemical mechanism
    • Whether interaction is direct unknown
  6. 2010 High

    Resolved MED10 as a bridging subunit that links the middle and tail modules via direct Med7 and Med4 binding, and confirmed its conserved role beyond transcription in VDR-dependent keratinocyte biology.

    Evidence Reconstituted recombinant/endogenous middle module with native and ion-mobility MS, SAXS, light scattering and interaction assays; siRNA knockdown with proliferation/differentiation readouts in keratinocytes

    PMID:20123732 PMID:20520624

    Open questions at the time
    • Atomic-resolution structure of MED10 not determined
    • Mechanistic link between module bridging and VDR output unresolved
  7. 2013 Medium

    Positioned MED10 architecturally within an extended, flexible middle module flanking the Med7/Med21 heterodimer.

    Evidence Lysine-lysine cross-linking mass spectrometry with crystal structure docking and homology modeling

    PMID:23939621

    Open questions at the time
    • No mutagenesis validation of MED10 cross-link contacts
    • Model relies partly on homology inference
  8. 2016 High

    Identified the mechanistic basis of MED10's essential transcriptional role: a direct functional interaction with TFIIB required for preinitiation complex assembly genome-wide, while in vivo establishing it as a node directing developmental signaling pathway outputs.

    Evidence In vivo genetics, in vitro PIC assembly, genome-wide chromatin analysis and TFIIB epistasis in yeast; zebrafish insertional mutant with Tbx2b/Foxn4 rescue and expression analysis

    PMID:27343557 PMID:27688401

    Open questions at the time
    • Structural detail of the Med10-TFIIB interface not solved
    • How PIC-assembly function relates to activator selectivity not integrated
  9. 2025 Medium

    Extended MED10 to an oncogenic driver in carcinoma, acting through RAF1/MEK/ERK/c-Myc activation and PTEN ubiquitination-mediated degradation that confers chemoresistance.

    Evidence CRISPR knockout and overexpression with proliferation/migration/invasion assays, Western blot, RT-qPCR, flow cytometry, TAK-243 ubiquitination rescue, and xenograft models in bladder and hepatocellular carcinoma

    PMID:35096564 PMID:40183262 PMID:40917057

    Open questions at the time
    • Direct biochemical MED10-RAF1 interaction not reconstituted
    • Mechanism by which MED10 promotes PTEN ubiquitination not defined
    • Whether oncogenic effects depend on Mediator transcriptional function unresolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • How MED10's structural bridging and TFIIB-dependent PIC-assembly function mechanistically translate into activator/pathway-selective and oncogenic outputs remains unresolved.
  • No high-resolution structure of MED10 itself
  • Direct enzymatic/recruitment mechanism for cancer-context PTEN degradation unknown
  • Connection between Mediator role and RAF1 axis activation undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 3 GO:0005198 structural molecule activity 2 GO:0060090 molecular adaptor activity 2
Localization
GO:0005634 nucleus 1
Pathway
R-HSA-1643685 Disease 3 R-HSA-74160 Gene expression (Transcription) 3 R-HSA-1266738 Developmental Biology 2 R-HSA-162582 Signal Transduction 2
Partners
MED21MED4MED7TFIIB
Complex memberships
Mediator complex (middle module)Rgr1 subcomplexSMCC complex

Evidence

Reading pass · 18 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1998 MED10 (NUT2) was identified as a subunit of the yeast Mediator complex, verified by copurification and co-immunoprecipitation with RNA polymerase II holoenzyme. Peptide sequence determination, copurification, co-immunoprecipitation The Journal of biological chemistry High 9812975
1998 NUT2 (MED10) encodes a nuclear protein that cooperates with NUT1 to negatively regulate transcription; the NUT2 gene is essential in S. cerevisiae, and inactivation of a temperature-sensitive NUT2 allele alone causes constitutive, Swi4p-independent expression of reporter genes. Genetic analysis, temperature-sensitive allele inactivation, lacZ reporter assays, nuclear localization by cell biology Molecular and cellular biology Medium 9671481
1999 Med10/Nut2 is a subunit of the Rgr1 subcomplex of yeast Mediator and is specifically required for Gcn4-mediated transcription of amino acid biosynthetic genes, demonstrating an activator-specific requirement distinct from the global requirement of Med6. Cloning of mediator subunits, differential display and Northern analysis of mRNAs from wild-type and Mediator mutant cells Molecular and cellular biology Medium 9891034
1999 Human NUT2 (MED10) was identified as a component of the SMCC complex (a human SRB/MED-containing cofactor), which can repress activator-dependent transcription or act synergistically with PC4 to enhance it, and which shows direct activator interactions but can act independently of the RNA polymerase II CTD. Biochemical purification of human complex, functional transcription assays (repression and activation), direct activator interaction assays Molecular cell Medium 10024883
2001 The Rgr1 subcomplex of yeast Mediator has modular structure comprising the Gal11, Med9/Cse2, and Med10/Nut2 modules; the Med10/Nut2 module is specifically required for transcriptional repression of a distinct group of genes; the transcriptional repressor Tup1 binds to the Gal11 module at regions overlapping with transcriptional activator binding sites. Biochemical subunit composition analysis, genome-wide gene expression analysis, Northern analysis, GST pull-down The Journal of biological chemistry Medium 11470794
2004 Human MED10 (NUT2) was confirmed as a consensus subunit of the mammalian Mediator complex by MudPIT proteomic analysis of Mediator preparations immunoaffinity-purified through MED10 itself, establishing its presence in the complex. Multidimensional protein identification technology (MudPIT), immunoaffinity purification Molecular cell High 15175163
2006 Med21 physically interacts with Med10 in the Mediator middle module; this interaction was confirmed by two-hybrid experiments and co-immunoprecipitation of tagged proteins produced in insect cells and E. coli, and depends strongly on amino acid residues 2–8 of Med21. Yeast two-hybrid, co-immunoprecipitation of recombinant proteins from insect cells and E. coli Molecular genetics and genomics Medium 16758199
2006 Zebrafish Med10 (a Mediator middle domain subunit) differentially transduces signals from distinct signaling pathways: reduction of Med10 levels enhances Wnt signaling and impairs Nodal signaling during embryogenesis, a dual role not shared by Med12/Med13 (Wnt only) or Med15 (Nodal only). Positional cloning of zebrafish mutant, morpholino antisense oligonucleotide knockdown, pathway-specific phenotypic readouts during embryogenesis Developmental biology Medium 17208216
2007 Reducing the level of essential Mediator subunit Nut2 (MED10) suppresses the growth defect caused by depletion of the transcriptional repressor NC2 in S. cerevisiae, placing MED10/Nut2 as an antagonistic component relative to NC2 in basal transcription control. Genetic suppressor analysis, reduction of Nut2 levels, growth assays Genetics Low 17339209
2010 The Mediator middle module from S. cerevisiae consists of seven subunits (Med1, 4, 7, 9, 10, 21, 31) in equimolar stoichiometry; Med10 bridges to the Mediator tail module by binding to both Med7 and Med4, as determined by protein-protein interaction assays. Recombinant and endogenous module preparation, native mass spectrometry, ion-mobility MS, light scattering, SAXS, protein-protein interaction assays Nucleic acids research High 20123732
2010 MED10 silencing in primary keratinocytes has an inhibitory role on VDR-mediated keratinocyte proliferation and differentiation, in contrast to the stimulatory roles of MED1 and MED21, as determined by siRNA knockdown and functional assays. siRNA knockdown, keratinocyte proliferation and differentiation assays, VDR affinity bead purification + mass spectrometry The Journal of investigative dermatology Medium 20520624
2011 The bundle domain fold predicted for Med10/Med14 (and other Mediator heterodimers) represents a common four-helix bundle building block in Mediator, based on structural analysis of the Med11/22 heterodimer and homology predictions for the middle module. Crystal structure of Med11/22, homology modeling, in vitro transcription pre-initiation complex formation assay, in vivo mutagenesis Nucleic acids research Low 21498544
2013 A 3D model of the 6-subunit Mediator middle module positions Med10 flanking the Med7/Med21 heterodimer within an extended, flexible architecture, based on cross-linking mass spectrometry and crystal/homology model docking. Lysine-lysine chemical cross-linking, mass spectrometry, crystal structure docking, homology modeling Nucleic acids research Medium 23939621
2016 The Mediator middle module exerts an essential function in preinitiation complex (PIC) assembly genome-wide through its Med10 subunit via a key interaction with TFIIB; this Mediator–TFIIB link was shown by in vivo, in vitro, and genome-wide (in silico) approaches. In vivo genetic analysis, in vitro PIC assembly assay, genome-wide ChIP/chromatin analysis, epistasis with TFIIB Genes & development High 27688401
2016 Zebrafish Med10 is required for heart valve formation; loss of Med10 (ping pong mutant) reduces Tbx2b expression and abolishes Has2 expression, impairing cardiac jelly development; rescue by Tbx2b but not by Foxn4 overexpression places Med10 downstream of Foxn4 and upstream of Tbx2b in this pathway. Insertional promoter mutation characterization, rescue experiments (Tbx2b/Foxn4 overexpression), expression analysis, zebrafish cardiac valve phenotype Biochemical and biophysical research communications Medium 27343557
2022 MED10 knockout in bladder urothelial carcinoma cell lines (SW1738 and JMSU1) attenuates cell proliferation, migration, invasion, clonogenicity, and tumorsphere formation, with downregulation of BCL-xL, MKI67, VIM, SNAI1, OCT4, LIN28A and upregulation of BAX; MED10 interacts with and co-expresses with hsa-miR-590, and CRISPR-mediated MED10 knockout downregulates miR-590. CRISPR-mediated knockout, cell proliferation/migration/invasion/clonogenicity assays, Western blot protein expression analysis Frontiers in oncology Medium 35096564
2025 MED10 overexpression drives HCC cell cycle progression and proliferation by activating RAF1, potentially through the MEK/ERK/c-Myc signaling axis; MED10 also promotes epithelial-mesenchymal transition (EMT) and cell migration in HCC cells. In vitro overexpression/knockdown, cell cycle flow cytometry, proliferation assays (CCK-8, colony formation, EdU), migration assays (transwell, wound healing), RT-qPCR, Western blot, immunofluorescence, in vivo xenograft model Frontiers in bioscience (Landmark edition) Medium 40917057
2025 MED10 promotes PTEN ubiquitination (post-translational degradation) in HCC cells, reducing PTEN protein levels without affecting PTEN mRNA, thereby enhancing cisplatin resistance; this effect is reversed by ubiquitination inhibitor TAK-243 and confirmed in xenograft models. Western blot for PTEN protein/mRNA, ubiquitination inhibitor (TAK-243) rescue, MED10 overexpression/knockdown, cell viability assay (IC50), flow cytometry apoptosis, in vivo xenograft Current cancer drug targets Medium 40183262

Source papers

Stage 0 corpus · 37 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2004 A set of consensus mammalian mediator subunits identified by multidimensional protein identification technology. Molecular cell 266 15175163
1999 A novel human SRB/MED-containing cofactor complex, SMCC, involved in transcription regulation. Molecular cell 233 10024883
2001 Multiple regulators of Ty1 transposition in Saccharomyces cerevisiae have conserved roles in genome maintenance. Genetics 208 11779788
1999 Expression of basement membrane antigens and matrix metalloproteinases 2 and 9 in cutaneous basal and squamous cell carcinomas. Anticancer research 73 10652575
1999 Activator-specific requirement of yeast mediator proteins for RNA polymerase II transcriptional activation. Molecular and cellular biology 73 9891034
2005 Determination of the 'critical region' for cat-like cry of Cri-du-chat syndrome and analysis of candidate genes by quantitative PCR. European journal of human genetics : EJHG 55 15657623
1998 Identification of new mediator subunits in the RNA polymerase II holoenzyme from Saccharomyces cerevisiae. The Journal of biological chemistry 48 9812975
1998 Nuclear proteins Nut1p and Nut2p cooperate to negatively regulate a Swi4p-dependent lacZ reporter gene in Saccharomyces cerevisiae. Molecular and cellular biology 45 9671481
2011 Mediator head subcomplex Med11/22 contains a common helix bundle building block with a specific function in transcription initiation complex stabilization. Nucleic acids research 38 21498544
2013 Model of the Mediator middle module based on protein cross-linking. Nucleic acids research 37 23939621
2001 Med9/Cse2 and Gal11 modules are required for transcriptional repression of distinct group of genes. The Journal of biological chemistry 37 11470794
2010 Preparation and topology of the Mediator middle module. Nucleic acids research 36 20123732
2000 Purification and characterization of RNA polymerase II holoenzyme from Schizosaccharomyces pombe. The Journal of biological chemistry 35 10625684
2016 Functional interplay between Mediator and TFIIB in preinitiation complex assembly in relation to promoter architecture. Genes & development 32 27688401
2010 The transcriptional coactivator DRIP/mediator complex is involved in vitamin D receptor function and regulates keratinocyte proliferation and differentiation. The Journal of investigative dermatology 31 20520624
1991 Interaction of parasitism and nutrition and their effects on production and clinical parameters in goats. Veterinary parasitology 31 1763494
2006 Depletion of Med10 enhances Wnt and suppresses Nodal signaling during zebrafish embryogenesis. Developmental biology 28 17208216
1988 Culture of putative Langerhans cell bone marrow precursors: characterization of their phenotype. Experimental hematology 27 3169159
1986 Subclustering of CD1 monoclonal antibodies based on the reactivity on human Langerhans cells. Immunology letters 24 2424832
2016 The mediator complex subunit Med10 regulates heart valve formation in zebrafish by controlling Tbx2b-mediated Has2 expression and cardiac jelly formation. Biochemical and biophysical research communications 22 27343557
1990 CD1 stimulation of human T cell lines induces a rapid increase in the intracellular free Ca2+ concentration and the production of IL-2. Journal of immunology (Baltimore, Md. : 1950) 20 1690769
2019 Integrated analysis of the critical region 5p15.3-p15.2 associated with cri-du-chat syndrome. Genetics and molecular biology 19 30985858
2006 Functional and physical interactions within the middle domain of the yeast mediator. Molecular genetics and genomics : MGG 18 16758199
2021 Development of a novel lipid metabolism-based risk score model in hepatocellular carcinoma patients. BMC gastroenterology 17 33579192
1992 Interaction of parasitism and nutrition in goats: effects on haematological parameters, correlations, and other statistical associations. Veterinary parasitology 15 1466129
2010 New suppressors of THO mutations identify Thp3 (Ypr045c)-Csn12 as a protein complex involved in transcription elongation. Molecular and cellular biology 14 21149575
2007 Specific defects in different transcription complexes compensate for the requirement of the negative cofactor 2 repressor in Saccharomyces cerevisiae. Genetics 11 17339209
2001 The MED-7 transcriptional mediator encoded by let-49 is required for gonad and germ cell development in Caenorhabditis elegans. FEBS letters 10 11728440
2019 Interactome Analysis of the Differentially Expressed Proteins in Uterine Leiomyoma. Anti-cancer agents in medicinal chemistry 8 30727917
2022 MED10 Drives the Oncogenicity and Refractory Phenotype of Bladder Urothelial Carcinoma Through the Upregulation of hsa-miR-590. Frontiers in oncology 6 35096564
2023 Three-dimensional chromatin landscapes in hepatocellular carcinoma associated with hepatitis B virus. Journal of gastroenterology 5 37925679
2013 A gene trap mutagenesis screen for genes underlying cellular response to the mood stabilizer lithium. Journal of cellular and molecular medicine 2 23577691
2025 MED10 Increases Cisplatin Resistance by Promoting PTEN Ubiquitination of Hepatocellular Carcinoma. Current cancer drug targets 1 40183262
2025 MED10 as a Novel Oncogenic Driver in HCC: Promoting Cell Cycle Progression and Proliferation Through RAF1 Activation. Frontiers in bioscience (Landmark edition) 1 40917057
1994 Altered expression of NU-T2-BMZ antigen and type VII collagen in basal cell epithelioma. Journal of dermatological science 1 8060915
1996 Monoclonal antibodies (NU-T1 and NU-T2) recognizing antigens expressed on human T cells. The Kurume medical journal 0 8709556
1995 Altered expression of a new antigen of the dermal-epidermal junction (NU-T2 DEJ Ag) in junctional epidermolysis bullosa. Archives of dermatological research 0 8554379

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