{"gene":"MED19","run_date":"2026-04-28T18:30:28","timeline":{"discoveries":[{"year":2006,"finding":"Med19 (Rox3) in S. cerevisiae is required for stable association of the Middle module with the rest of the Mediator complex; deletion of Med19 releases the entire Middle module under stringent conditions, leaving a stable Head-Tail complex that is defective in enhanced basal transcription, TFIIH-mediated CTD phosphorylation, and RNA Pol II binding, while activated transcription requires the Middle module.","method":"Purification of Mediator from Δmed19 yeast strains under mild and stringent conditions; in vitro transcription assays; CTD phosphorylation assays; RNA Pol II binding assays","journal":"The Journal of biological chemistry","confidence":"High","confidence_rationale":"Tier 1–2 — biochemical reconstitution/purification with multiple functional readouts in a single rigorous study","pmids":["17192271"],"is_preprint":false},{"year":2014,"finding":"Drosophila Med19 directly binds Hox transcription factor homeodomains in vitro and in vivo through a conserved animal-specific motif on Med19; loss-of-function Med19 mutations act as dose-sensitive genetic modifiers of Hox-directed developmental outcomes, and Med19 is required for Hox-dependent target gene activation in clonal analysis.","method":"In vitro binding assays, co-immunoprecipitation in vivo, clonal loss-of-function analysis, genetic modifier screen, mutagenesis of conserved Med19 motif","journal":"PLoS genetics","confidence":"High","confidence_rationale":"Tier 1–2 — direct in vitro binding + in vivo Co-IP + genetic epistasis + mutagenesis of functional motif in a single study","pmids":["24786462"],"is_preprint":false},{"year":2020,"finding":"Med19 physically interacts with Drosophila GATA transcription factors (Pannier and Serpent) in vivo and in vitro through their conserved C-terminal zinc finger domains, and is required for GATA-driven gene expression; Med19 also directly interacts with Med1 by GST pulldown, indicating privileged contacts between these two Middle module subunits.","method":"Co-immunoprecipitation in vivo, in vitro binding assays, GST pulldown, loss-of-function genetics in vivo, RNAi in cellulo with gene expression readouts","journal":"The Journal of biological chemistry","confidence":"High","confidence_rationale":"Tier 1–2 — reciprocal in vitro and in vivo binding assays combined with functional loss-of-function data","pmids":["32737196"],"is_preprint":false},{"year":2022,"finding":"In Drosophila wing imaginal discs, Med19 is not globally required for mRNA transcription but selectively regulates less than a quarter of expressed genes; Med19-dependent genes are enriched for spatially regulated developmental genes and transcription factors, and Med19 is specifically required for Notch-responsive gene expression (wingless and E(spl)-C genes).","method":"Auxin-inducible degradation of endogenous Med19 in vivo coupled with RNA-seq; genetic epistasis with Notch pathway","journal":"PloS one","confidence":"High","confidence_rationale":"Tier 1–2 — inducible endogenous protein degradation combined with genome-wide transcriptomics provides clean mechanistic resolution","pmids":["36445897"],"is_preprint":false},{"year":2025,"finding":"MED19 localizes to the nucleolus independently of the Mediator complex; this nucleolar targeting is mediated by a conserved C-terminal poly-lysine motif that enables binding to ribosomal RNA and fibrillarin (FBL), a 2'-O-methyltransferase component; MED19 facilitates rRNA 2'-O-methylation and rRNA processing, thereby promoting IRES-dependent translation of onco-promoting mRNAs including c-Myc.","method":"Subcellular fractionation, co-immunoprecipitation with FBL, RNA binding assays, mutagenesis of poly-lysine motif, rRNA methylation assays, IRES-reporter translation assays","journal":"Nucleic acids research","confidence":"High","confidence_rationale":"Tier 1–2 — multiple orthogonal methods (fractionation, Co-IP, mutagenesis, functional methylation and translation assays) in a single study","pmids":["41414671"],"is_preprint":false},{"year":2018,"finding":"MED19 interacts with EGFR and increases EGFR expression, activating the EGFR/MEK/ERK signaling pathway to promote breast cancer cell proliferation, EMT, invasion and migration; MED19 expression is negatively regulated by miR-101-3p and miR-422a.","method":"Co-immunoprecipitation, western blot, lentiviral knockdown/overexpression, in vitro and in vivo functional assays, dual-luciferase reporter assay","journal":"Cancer letters","confidence":"Medium","confidence_rationale":"Tier 2–3 — single lab with Co-IP and functional assays but limited mechanistic depth on direct interaction","pmids":["30583076"],"is_preprint":false},{"year":2018,"finding":"MED19 promotes chemoresistance in breast cancer by facilitating autophagy through the HMGB1 pathway; Med19 knockdown reduces LC3-II/LC3-I ratio, Atg3, Atg5 expression, and autophagic flux, and increases sensitivity to adriamycin, cisplatin, and taxol.","method":"Lentivirus-mediated MED19 knockdown, autophagy marker western blot (LC3, p62, Atg3, Atg5), RFP-LC3 dot formation assay, drug sensitivity assays in ADM-resistant cells","journal":"Journal of cellular biochemistry","confidence":"Medium","confidence_rationale":"Tier 3 — single lab with multiple phenotypic readouts but HMGB1 link relies on pathway inference without direct biochemical demonstration","pmids":["30161287"],"is_preprint":false},{"year":2017,"finding":"MED19 knockdown in bladder cancer cells suppresses cell proliferation and migration by downregulating the Wnt/β-catenin pathway, reducing Wnt2, β-catenin, Cyclin-D1, and MMP-9 while elevating GSK3β and E-cadherin levels.","method":"shRNA knockdown, TOP/FOPflash Wnt reporter assay, western blot, in vitro functional assays, xenograft tumor model","journal":"Journal of cellular and molecular medicine","confidence":"Medium","confidence_rationale":"Tier 3 — reporter assay and KD functional data from single lab; pathway placement is indirect","pmids":["28631286"],"is_preprint":false},{"year":2016,"finding":"MED19 promotes breast cancer cell proliferation by suppressing CBFA2T3, which in turn increases HEB expression; MED19 knockdown upregulates CBFA2T3 and downregulates HEB, and overexpression of CBFA2T3 reverses the proliferative effect of MED19 overexpression.","method":"Lentiviral knockdown and ectopic overexpression, qRT-PCR, western blot, CCK8 and colony formation assays, epistasis rescue experiment","journal":"Breast cancer (Tokyo, Japan)","confidence":"Medium","confidence_rationale":"Tier 3 — single lab with genetic epistasis rescue but no direct biochemical interaction demonstrated","pmids":["27572702"],"is_preprint":false},{"year":2017,"finding":"MED19 knockdown induces apoptosis in laryngocarcinoma HEp2 cells via activation of caspase-3, caspase-9, and Apaf-1.","method":"shRNA knockdown, caspase activity assays, western blot, flow cytometry, xenograft assay","journal":"American journal of translational research","confidence":"Low","confidence_rationale":"Tier 3 — single lab, single KD approach with phenotypic but limited mechanistic depth","pmids":["28337304"],"is_preprint":false},{"year":2011,"finding":"MED19 knockdown in prostate cancer cells causes S-phase arrest and induces apoptosis via modulation of Bid and Caspase-7.","method":"Lentivirus-mediated shRNA knockdown, flow cytometry, western blot, colony formation, xenograft assay","journal":"BMB reports","confidence":"Low","confidence_rationale":"Tier 3 — single lab, single KD method; mechanistic link to Bid/Caspase-7 not biochemically validated","pmids":["21871180"],"is_preprint":false},{"year":2017,"finding":"LCMR1 (MED19) interacts with the chromatin-associated protein DEK in lung cancer cells; the interaction is mediated primarily by the N-terminal region of DEK, and both proteins cooperate to suppress apoptosis via the MCL-1 pathway.","method":"Yeast two-hybrid screen, co-immunoprecipitation, GST pulldown, RNAi knockdown with apoptosis readouts","journal":"Molecular medicine reports","confidence":"Medium","confidence_rationale":"Tier 2 — reciprocal Co-IP and GST pulldown establish direct interaction; functional cooperation confirmed by RNAi epistasis","pmids":["28765911"],"is_preprint":false},{"year":2016,"finding":"LCMR1 (MED19) identified as a positive transcriptional regulator of Tspan8 in melanoma cells; LCMR1 modulation positively regulates endogenous Tspan8 expression with concomitant changes in cell-matrix adherence and invasion.","method":"Large-scale RNAi screen, lentiviral knockdown/overexpression, invasion and adherence assays, in vivo tumorigenicity","journal":"Oncogene","confidence":"Low","confidence_rationale":"Tier 3 — functional link established by RNAi screen and KD/OE, but direct transcriptional mechanism not biochemically demonstrated","pmids":["27375018"],"is_preprint":false},{"year":2023,"finding":"LCMR1 (MED19) diminishes RNA Pol II occupancy at promoters of HLA-encoding genes to suppress their transcription, thereby promoting immune evasion in large-cell lung cancer cells.","method":"Lentivirus-based knockdown, Pol II occupancy assay (multiple sequence-based assay), xenograft tumor model, TCGA correlation analysis","journal":"Cancers","confidence":"Low","confidence_rationale":"Tier 3 — Pol II occupancy data supports the mechanistic claim but single lab and limited biochemical detail","pmids":["38001705"],"is_preprint":false}],"current_model":"MED19 is an integral Mediator complex subunit that stabilizes inter-module interactions (particularly anchoring the Middle module) and serves as a direct physical interface between Mediator and sequence-specific transcription factors (Hox homeodomains, GATA zinc fingers) to selectively activate developmental and signal-responsive RNA Pol II-dependent genes; additionally, MED19 localizes to the nucleolus via a C-terminal poly-lysine motif where, independently of the Mediator complex, it binds fibrillarin and rRNA to promote 2'-O-methylation and IRES-dependent translation of oncoproteins such as c-Myc."},"narrative":{"teleology":[{"year":2006,"claim":"Establishing that MED19 is the structural linchpin holding the Middle module within the Mediator complex answered the fundamental question of how this multisubunit coactivator maintains its modular architecture and provided the first mechanistic explanation for why loss of a single subunit can disconnect an entire functional module.","evidence":"Purification of Mediator from Δmed19 yeast strains under varying stringency, in vitro transcription, CTD phosphorylation, and Pol II binding assays","pmids":["17192271"],"confidence":"High","gaps":["Structural contacts between MED19 and individual Middle module subunits not mapped at residue resolution","Whether the bridging role is conserved in metazoan Mediator was not tested"]},{"year":2014,"claim":"Demonstrating that MED19 directly binds Hox homeodomains through a conserved animal-specific motif resolved how a general coactivator subunit can provide transcription-factor-specific selectivity, establishing MED19 as a dedicated activator interface for Hox-dependent developmental gene regulation.","evidence":"In vitro binding, in vivo Co-IP, clonal loss-of-function analysis, genetic modifier screen, and mutagenesis of conserved Med19 motif in Drosophila","pmids":["24786462"],"confidence":"High","gaps":["Whether the same motif also contacts non-Hox homeodomain factors was not tested","Structural basis of the Hox–MED19 interface remains unresolved"]},{"year":2017,"claim":"Identification of DEK as a direct MED19-interacting chromatin-associated partner, and observations that MED19 knockdown modulates Wnt/β-catenin pathway output in cancer cells, expanded MED19's functional network beyond classical transcription factor contacts, though the directness of signaling pathway effects remains uncertain.","evidence":"Yeast two-hybrid, reciprocal Co-IP and GST pulldown for DEK interaction; shRNA knockdown with Wnt reporter assays in bladder cancer cells","pmids":["28765911","28631286"],"confidence":"Medium","gaps":["Whether MED19–DEK interaction occurs on chromatin at specific loci is unknown","Wnt pathway effects may be indirect consequences of general Mediator transcriptional activity","No structural or domain-mapping data for MED19–DEK beyond N-terminal DEK region"]},{"year":2018,"claim":"Reports that MED19 interacts with EGFR and modulates EGFR/MEK/ERK signaling, and separately promotes autophagy-mediated chemoresistance, indicated that MED19 perturbation broadly affects oncogenic signaling outputs in breast cancer, though direct biochemical mechanisms linking MED19 to these pathways remained unclear.","evidence":"Co-IP, lentiviral knockdown/overexpression, drug sensitivity assays, and autophagy marker analysis in breast cancer cell lines","pmids":["30583076","30161287"],"confidence":"Medium","gaps":["Whether MED19–EGFR interaction is direct or bridged through Mediator is not resolved","HMGB1-autophagy link is inferred from marker changes, not demonstrated biochemically","Single-lab findings without independent replication"]},{"year":2020,"claim":"Extending the transcription factor interface model, demonstration that MED19 directly binds GATA zinc-finger domains (Pannier, Serpent) and also contacts the Middle module subunit Med1 established MED19 as a multi-input hub that integrates diverse activator signals through the same Mediator subunit.","evidence":"Reciprocal in vitro binding and in vivo Co-IP, GST pulldown for Med1 interaction, RNAi-based gene expression assays in Drosophila","pmids":["32737196"],"confidence":"High","gaps":["Whether Hox and GATA factors compete or cooperate for the same MED19 surface is unknown","Mammalian GATA–MED19 interaction not tested"]},{"year":2022,"claim":"Acute endogenous MED19 degradation coupled with transcriptomics resolved the long-standing question of whether MED19 is a global or gene-selective coactivator, demonstrating that it is dispensable for the majority of transcription but specifically required for Notch-responsive and spatially regulated developmental genes.","evidence":"Auxin-inducible degradation of endogenous Med19 in Drosophila wing discs with RNA-seq and Notch pathway epistasis","pmids":["36445897"],"confidence":"High","gaps":["Mechanism by which MED19 confers Notch-pathway specificity (direct Notch ICD contact or indirect) is not established","Whether selective gene dependence reflects enhancer architecture or activator identity is unresolved"]},{"year":2025,"claim":"Discovery of a Mediator-independent nucleolar function for MED19 — binding fibrillarin and rRNA via a C-terminal poly-lysine motif to promote 2′-O-methylation and IRES-dependent translation — fundamentally expanded MED19's functional repertoire beyond transcriptional coactivation into ribosome biogenesis and translational control.","evidence":"Subcellular fractionation, Co-IP with fibrillarin, RNA binding assays, poly-lysine motif mutagenesis, rRNA methylation assays, IRES-reporter translation assays in human cells","pmids":["41414671"],"confidence":"High","gaps":["Which specific rRNA 2′-O-methylation sites are MED19-dependent is not catalogued","Whether nucleolar MED19 functions are relevant in non-cancer developmental contexts is untested","Relative contribution of transcriptional vs. translational MED19 functions to oncogenesis is unresolved"]},{"year":null,"claim":"A high-resolution structural model of MED19 within the intact mammalian Mediator–Pol II PIC, and the molecular basis by which MED19 distinguishes its Mediator-dependent transcriptional role from its Mediator-independent nucleolar function, remain to be established.","evidence":"","pmids":[],"confidence":"High","gaps":["No cryo-EM or crystal structure of MED19 bound to a transcription factor or to fibrillarin","Mechanism partitioning MED19 between Mediator and nucleolar pools is unknown","Whether mammalian MED19 retains the Hox/GATA-binding motif and gene-selective coactivation is not directly demonstrated"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0140110","term_label":"transcription regulator activity","supporting_discovery_ids":[0,1,2,3]},{"term_id":"GO:0003723","term_label":"RNA binding","supporting_discovery_ids":[4]},{"term_id":"GO:0060090","term_label":"molecular adaptor activity","supporting_discovery_ids":[0,1,2]}],"localization":[{"term_id":"GO:0005634","term_label":"nucleus","supporting_discovery_ids":[0,1,3]},{"term_id":"GO:0005730","term_label":"nucleolus","supporting_discovery_ids":[4]}],"pathway":[{"term_id":"R-HSA-74160","term_label":"Gene expression (Transcription)","supporting_discovery_ids":[0,1,2,3]},{"term_id":"R-HSA-8953854","term_label":"Metabolism of RNA","supporting_discovery_ids":[4]},{"term_id":"R-HSA-392499","term_label":"Metabolism of proteins","supporting_discovery_ids":[4]},{"term_id":"R-HSA-1266738","term_label":"Developmental Biology","supporting_discovery_ids":[1,2,3]}],"complexes":["Mediator complex (Middle module)"],"partners":["MED1","FBL","DEK","EGFR"],"other_free_text":[]},"mechanistic_narrative":"MED19 is a subunit of the Mediator complex that functions both as a structural bridge stabilizing the Middle module within the holocomplex and as a selective transcriptional coactivator that physically interfaces with sequence-specific transcription factors to control developmental and signal-responsive gene expression. In yeast, MED19 is required for stable Middle module association with the Head–Tail complex and for enhanced basal transcription, TFIIH-mediated CTD phosphorylation, and RNA Pol II recruitment [PMID:17192271]; in metazoans, MED19 directly binds Hox homeodomains and GATA zinc-finger domains through a conserved animal-specific motif to activate developmental target genes, and selectively regulates a subset of genes including Notch-responsive targets rather than serving as a global transcriptional requirement [PMID:24786462, PMID:32737196, PMID:36445897]. Independent of the Mediator complex, MED19 localizes to the nucleolus via a C-terminal poly-lysine motif, where it binds fibrillarin and rRNA to promote 2′-O-methylation and IRES-dependent translation of oncoproteins such as c-Myc [PMID:41414671]."},"prefetch_data":{"uniprot":{"accession":"A0JLT2","full_name":"Mediator of RNA polymerase II transcription subunit 19","aliases":["Lung cancer metastasis-related protein 1","Mediator complex subunit 19"],"length_aa":244,"mass_kda":26.3,"function":"Component of the Mediator complex, a coactivator involved in the regulated transcription of nearly all RNA polymerase II-dependent genes. Mediator functions as a bridge to convey information from gene-specific regulatory proteins to the basal RNA polymerase II transcription machinery. Mediator is recruited to promoters by direct interactions with regulatory proteins and serves as a scaffold for the assembly of a functional preinitiation complex with RNA polymerase II and the general transcription factors","subcellular_location":"Nucleus","url":"https://www.uniprot.org/uniprotkb/A0JLT2/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/MED19","classification":"Not Classified","n_dependent_lines":692,"n_total_lines":1208,"dependency_fraction":0.5728476821192053},"opencell":{"profiled":true,"resolved_as":"","ensg_id":"ENSG00000156603","cell_line_id":"CID000248","localizations":[{"compartment":"nuclear_punctae","grade":3},{"compartment":"nucleoplasm","grade":3}],"interactors":[{"gene":"MED14","stoichiometry":10.0},{"gene":"MED27","stoichiometry":10.0},{"gene":"MED23","stoichiometry":10.0},{"gene":"MED4","stoichiometry":10.0},{"gene":"TADA2B","stoichiometry":10.0},{"gene":"MED1","stoichiometry":10.0},{"gene":"MED13","stoichiometry":10.0},{"gene":"MED9","stoichiometry":10.0},{"gene":"MED31","stoichiometry":10.0},{"gene":"MED16","stoichiometry":10.0}],"url":"https://opencell.sf.czbiohub.org/target/CID000248","total_profiled":1310},"omim":[{"mim_id":"612385","title":"MEDIATOR COMPLEX SUBUNIT 19; MED19","url":"https://www.omim.org/entry/612385"},{"mim_id":"612382","title":"MEDIATOR COMPLEX SUBUNIT 10; MED10","url":"https://www.omim.org/entry/612382"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Supported","locations":[{"location":"Nuclear bodies","reliability":"Supported"},{"location":"Nucleoplasm","reliability":"Additional"}],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in all","driving_tissues":[],"url":"https://www.proteinatlas.org/search/MED19"},"hgnc":{"alias_symbol":["LCMR1"],"prev_symbol":[]},"alphafold":{"accession":"A0JLT2","domains":[{"cath_id":"-","chopping":"85-110_118-134","consensus_level":"medium","plddt":82.9023,"start":85,"end":134}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/A0JLT2","model_url":"https://alphafold.ebi.ac.uk/files/AF-A0JLT2-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-A0JLT2-F1-predicted_aligned_error_v6.png","plddt_mean":64.81},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=MED19","jax_strain_url":"https://www.jax.org/strain/search?query=MED19"},"sequence":{"accession":"A0JLT2","fasta_url":"https://rest.uniprot.org/uniprotkb/A0JLT2.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/A0JLT2/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/A0JLT2"}},"corpus_meta":[{"pmid":"17192271","id":"PMC_17192271","title":"Med19(Rox3) regulates Intermodule interactions in the Saccharomyces cerevisiae mediator complex.","date":"2006","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/17192271","citation_count":54,"is_preprint":false},{"pmid":"30583076","id":"PMC_30583076","title":"Med19 is targeted by miR-101-3p/miR-422a and promotes breast cancer progression by regulating the EGFR/MEK/ERK signaling pathway.","date":"2018","source":"Cancer letters","url":"https://pubmed.ncbi.nlm.nih.gov/30583076","citation_count":40,"is_preprint":false},{"pmid":"27811858","id":"PMC_27811858","title":"The FOXD3/miR-214/MED19 axis suppresses tumour growth and metastasis in human colorectal cancer.","date":"2016","source":"British journal of cancer","url":"https://pubmed.ncbi.nlm.nih.gov/27811858","citation_count":39,"is_preprint":false},{"pmid":"24786462","id":"PMC_24786462","title":"Drosophila melanogaster Hox transcription factors access the RNA polymerase II machinery through direct homeodomain binding to a conserved motif of mediator subunit Med19.","date":"2014","source":"PLoS genetics","url":"https://pubmed.ncbi.nlm.nih.gov/24786462","citation_count":37,"is_preprint":false},{"pmid":"20890603","id":"PMC_20890603","title":"Lentivirus-mediated inhibition of Med19 suppresses growth of breast cancer cells in vitro.","date":"2010","source":"Cancer chemotherapy and pharmacology","url":"https://pubmed.ncbi.nlm.nih.gov/20890603","citation_count":35,"is_preprint":false},{"pmid":"30161287","id":"PMC_30161287","title":"Med19 is involved in chemoresistance by mediating autophagy through HMGB1 in breast cancer.","date":"2018","source":"Journal of cellular biochemistry","url":"https://pubmed.ncbi.nlm.nih.gov/30161287","citation_count":31,"is_preprint":false},{"pmid":"23276457","id":"PMC_23276457","title":"Med19 promotes bone metastasis and invasiveness of bladder urothelial carcinoma via bone morphogenetic protein 2.","date":"2012","source":"Annals of diagnostic pathology","url":"https://pubmed.ncbi.nlm.nih.gov/23276457","citation_count":30,"is_preprint":false},{"pmid":"29795113","id":"PMC_29795113","title":"Inhibition of LCMR1 and ATG12 by demethylation-activated miR-570-3p is involved in the anti-metastasis effects of metformin on human osteosarcoma.","date":"2018","source":"Cell death & disease","url":"https://pubmed.ncbi.nlm.nih.gov/29795113","citation_count":26,"is_preprint":false},{"pmid":"21478038","id":"PMC_21478038","title":"Expression of Med19 in bladder cancer tissues and its role on bladder cancer cell growth.","date":"2011","source":"Urologic oncology","url":"https://pubmed.ncbi.nlm.nih.gov/21478038","citation_count":25,"is_preprint":false},{"pmid":"21372827","id":"PMC_21372827","title":"The role of Med19 in the proliferation and tumorigenesis of human hepatocellular carcinoma cells.","date":"2011","source":"Acta pharmacologica Sinica","url":"https://pubmed.ncbi.nlm.nih.gov/21372827","citation_count":24,"is_preprint":false},{"pmid":"21519921","id":"PMC_21519921","title":"MED19 promotes proliferation and tumorigenesis of lung cancer.","date":"2011","source":"Molecular and cellular biochemistry","url":"https://pubmed.ncbi.nlm.nih.gov/21519921","citation_count":23,"is_preprint":false},{"pmid":"33235461","id":"PMC_33235461","title":"The SP1-Induced Long Noncoding RNA, LINC00339, Promotes Tumorigenesis in Colorectal Cancer via the miR-378a-3p/MED19 Axis.","date":"2020","source":"OncoTargets and therapy","url":"https://pubmed.ncbi.nlm.nih.gov/33235461","citation_count":23,"is_preprint":false},{"pmid":"30473219","id":"PMC_30473219","title":"Role and mechanism of miR-4778-3p and its targets NR2C2 and Med19 in cervical cancer radioresistance.","date":"2018","source":"Biochemical and biophysical research communications","url":"https://pubmed.ncbi.nlm.nih.gov/30473219","citation_count":22,"is_preprint":false},{"pmid":"38371458","id":"PMC_38371458","title":"Hypoxic Bone Mesenchymal Stem Cell-Derived Exosomes Direct Schwann Cells Proliferation, Migration, and Paracrine to Accelerate Facial Nerve Regeneration via circRNA_Nkd2/miR-214-3p/MED19 Axis.","date":"2024","source":"International journal of nanomedicine","url":"https://pubmed.ncbi.nlm.nih.gov/38371458","citation_count":21,"is_preprint":false},{"pmid":"22565189","id":"PMC_22565189","title":"Med19 promotes gastric cancer progression and cellular growth.","date":"2012","source":"Gene","url":"https://pubmed.ncbi.nlm.nih.gov/22565189","citation_count":20,"is_preprint":false},{"pmid":"28631286","id":"PMC_28631286","title":"Knockdown of mediator subunit Med19 suppresses bladder cancer cell proliferation and migration by downregulating Wnt/β-catenin signalling pathway.","date":"2017","source":"Journal of cellular and molecular medicine","url":"https://pubmed.ncbi.nlm.nih.gov/28631286","citation_count":20,"is_preprint":false},{"pmid":"27572702","id":"PMC_27572702","title":"Med19 promotes breast cancer cell proliferation by regulating CBFA2T3/HEB expression.","date":"2016","source":"Breast cancer (Tokyo, Japan)","url":"https://pubmed.ncbi.nlm.nih.gov/27572702","citation_count":19,"is_preprint":false},{"pmid":"21306606","id":"PMC_21306606","title":"Overexpression of LCMR1 is significantly associated with clinical stage in human NSCLC.","date":"2011","source":"Journal of experimental & clinical cancer research : CR","url":"https://pubmed.ncbi.nlm.nih.gov/21306606","citation_count":19,"is_preprint":false},{"pmid":"21542455","id":"PMC_21542455","title":"Knockdown of MED19 by lentivirus-mediated shRNA in human osteosarcoma cells inhibits cell proliferation by inducing cell cycle arrest in the G0/G1 phase.","date":"2011","source":"Oncology research","url":"https://pubmed.ncbi.nlm.nih.gov/21542455","citation_count":17,"is_preprint":false},{"pmid":"27375018","id":"PMC_27375018","title":"A large-scale RNAi screen identifies LCMR1 as a critical regulator of Tspan8-mediated melanoma invasion.","date":"2016","source":"Oncogene","url":"https://pubmed.ncbi.nlm.nih.gov/27375018","citation_count":16,"is_preprint":false},{"pmid":"21871180","id":"PMC_21871180","title":"Suppression of MED19 expression by shRNA induces inhibition of cell proliferation and tumorigenesis in human prostate cancer cells.","date":"2011","source":"BMB reports","url":"https://pubmed.ncbi.nlm.nih.gov/21871180","citation_count":16,"is_preprint":false},{"pmid":"21732059","id":"PMC_21732059","title":"Suppression of lung cancer metastasis-related protein 1 (LCMR1) inhibits the growth of colorectal cancer cells.","date":"2011","source":"Molecular biology 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research","url":"https://pubmed.ncbi.nlm.nih.gov/28337304","citation_count":7,"is_preprint":false},{"pmid":"37650745","id":"PMC_37650745","title":"Chloroprocaine antagonizes progression of breast cancer by regulating LINC00494/miR-3619-5p/MED19 axis.","date":"2023","source":"Journal of biochemical and molecular toxicology","url":"https://pubmed.ncbi.nlm.nih.gov/37650745","citation_count":2,"is_preprint":false},{"pmid":"38001705","id":"PMC_38001705","title":"LCMR1 Promotes Large-Cell Lung Cancer Proliferation and Metastasis by Downregulating HLA-Encoding Genes.","date":"2023","source":"Cancers","url":"https://pubmed.ncbi.nlm.nih.gov/38001705","citation_count":1,"is_preprint":false},{"pmid":"40341970","id":"PMC_40341970","title":"LCMR1 deficiency exacerbates LPS‑induced lung injury in lung‑on‑a‑chip and mouse models.","date":"2025","source":"Molecular medicine reports","url":"https://pubmed.ncbi.nlm.nih.gov/40341970","citation_count":1,"is_preprint":false},{"pmid":"36445897","id":"PMC_36445897","title":"Inducible degradation of the Drosophila Mediator subunit Med19 reveals its role in regulating developmental but not constitutively-expressed genes.","date":"2022","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/36445897","citation_count":1,"is_preprint":false},{"pmid":"37065556","id":"PMC_37065556","title":"Deletion of LCMR1 in alveolar type II cells induces lethal impairment of lung structure and function in adult mice.","date":"2023","source":"Journal of thoracic disease","url":"https://pubmed.ncbi.nlm.nih.gov/37065556","citation_count":1,"is_preprint":false},{"pmid":"41414671","id":"PMC_41414671","title":"Nucleolar MED19 regulates 2'-O-methylation of rRNA in supporting cancer cell growth.","date":"2025","source":"Nucleic acids research","url":"https://pubmed.ncbi.nlm.nih.gov/41414671","citation_count":0,"is_preprint":false},{"pmid":"41866344","id":"PMC_41866344","title":"Mediator subunit MED19 modulates elf18-induced PR1 expression via TGA transcription factors.","date":"2026","source":"Plant signaling & behavior","url":"https://pubmed.ncbi.nlm.nih.gov/41866344","citation_count":0,"is_preprint":false},{"pmid":null,"id":"bio_10.1101_2025.06.18.659864","title":"The Mediator complex subunit Med19 extends healthy lifespan in <i>Drosophila</i> by preventing cellular and organismal frailty","date":"2025-06-18","source":"bioRxiv","url":"https://doi.org/10.1101/2025.06.18.659864","citation_count":0,"is_preprint":true}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":18623,"output_tokens":3263,"usd":0.052407},"stage2":{"model":"claude-opus-4-6","input_tokens":6668,"output_tokens":2503,"usd":0.143872},"total_usd":0.196279,"stage1_batch_id":"msgbatch_01Mgbec4vM6c9vXht7JVJzss","stage2_batch_id":"msgbatch_01JkuuH5RB2BdJNsgnhjbC6s","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2006,\n      \"finding\": \"Med19 (Rox3) in S. cerevisiae is required for stable association of the Middle module with the rest of the Mediator complex; deletion of Med19 releases the entire Middle module under stringent conditions, leaving a stable Head-Tail complex that is defective in enhanced basal transcription, TFIIH-mediated CTD phosphorylation, and RNA Pol II binding, while activated transcription requires the Middle module.\",\n      \"method\": \"Purification of Mediator from Δmed19 yeast strains under mild and stringent conditions; in vitro transcription assays; CTD phosphorylation assays; RNA Pol II binding assays\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1–2 — biochemical reconstitution/purification with multiple functional readouts in a single rigorous study\",\n      \"pmids\": [\"17192271\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"Drosophila Med19 directly binds Hox transcription factor homeodomains in vitro and in vivo through a conserved animal-specific motif on Med19; loss-of-function Med19 mutations act as dose-sensitive genetic modifiers of Hox-directed developmental outcomes, and Med19 is required for Hox-dependent target gene activation in clonal analysis.\",\n      \"method\": \"In vitro binding assays, co-immunoprecipitation in vivo, clonal loss-of-function analysis, genetic modifier screen, mutagenesis of conserved Med19 motif\",\n      \"journal\": \"PLoS genetics\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1–2 — direct in vitro binding + in vivo Co-IP + genetic epistasis + mutagenesis of functional motif in a single study\",\n      \"pmids\": [\"24786462\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"Med19 physically interacts with Drosophila GATA transcription factors (Pannier and Serpent) in vivo and in vitro through their conserved C-terminal zinc finger domains, and is required for GATA-driven gene expression; Med19 also directly interacts with Med1 by GST pulldown, indicating privileged contacts between these two Middle module subunits.\",\n      \"method\": \"Co-immunoprecipitation in vivo, in vitro binding assays, GST pulldown, loss-of-function genetics in vivo, RNAi in cellulo with gene expression readouts\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1–2 — reciprocal in vitro and in vivo binding assays combined with functional loss-of-function data\",\n      \"pmids\": [\"32737196\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"In Drosophila wing imaginal discs, Med19 is not globally required for mRNA transcription but selectively regulates less than a quarter of expressed genes; Med19-dependent genes are enriched for spatially regulated developmental genes and transcription factors, and Med19 is specifically required for Notch-responsive gene expression (wingless and E(spl)-C genes).\",\n      \"method\": \"Auxin-inducible degradation of endogenous Med19 in vivo coupled with RNA-seq; genetic epistasis with Notch pathway\",\n      \"journal\": \"PloS one\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1–2 — inducible endogenous protein degradation combined with genome-wide transcriptomics provides clean mechanistic resolution\",\n      \"pmids\": [\"36445897\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"MED19 localizes to the nucleolus independently of the Mediator complex; this nucleolar targeting is mediated by a conserved C-terminal poly-lysine motif that enables binding to ribosomal RNA and fibrillarin (FBL), a 2'-O-methyltransferase component; MED19 facilitates rRNA 2'-O-methylation and rRNA processing, thereby promoting IRES-dependent translation of onco-promoting mRNAs including c-Myc.\",\n      \"method\": \"Subcellular fractionation, co-immunoprecipitation with FBL, RNA binding assays, mutagenesis of poly-lysine motif, rRNA methylation assays, IRES-reporter translation assays\",\n      \"journal\": \"Nucleic acids research\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1–2 — multiple orthogonal methods (fractionation, Co-IP, mutagenesis, functional methylation and translation assays) in a single study\",\n      \"pmids\": [\"41414671\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"MED19 interacts with EGFR and increases EGFR expression, activating the EGFR/MEK/ERK signaling pathway to promote breast cancer cell proliferation, EMT, invasion and migration; MED19 expression is negatively regulated by miR-101-3p and miR-422a.\",\n      \"method\": \"Co-immunoprecipitation, western blot, lentiviral knockdown/overexpression, in vitro and in vivo functional assays, dual-luciferase reporter assay\",\n      \"journal\": \"Cancer letters\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2–3 — single lab with Co-IP and functional assays but limited mechanistic depth on direct interaction\",\n      \"pmids\": [\"30583076\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"MED19 promotes chemoresistance in breast cancer by facilitating autophagy through the HMGB1 pathway; Med19 knockdown reduces LC3-II/LC3-I ratio, Atg3, Atg5 expression, and autophagic flux, and increases sensitivity to adriamycin, cisplatin, and taxol.\",\n      \"method\": \"Lentivirus-mediated MED19 knockdown, autophagy marker western blot (LC3, p62, Atg3, Atg5), RFP-LC3 dot formation assay, drug sensitivity assays in ADM-resistant cells\",\n      \"journal\": \"Journal of cellular biochemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 — single lab with multiple phenotypic readouts but HMGB1 link relies on pathway inference without direct biochemical demonstration\",\n      \"pmids\": [\"30161287\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"MED19 knockdown in bladder cancer cells suppresses cell proliferation and migration by downregulating the Wnt/β-catenin pathway, reducing Wnt2, β-catenin, Cyclin-D1, and MMP-9 while elevating GSK3β and E-cadherin levels.\",\n      \"method\": \"shRNA knockdown, TOP/FOPflash Wnt reporter assay, western blot, in vitro functional assays, xenograft tumor model\",\n      \"journal\": \"Journal of cellular and molecular medicine\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 — reporter assay and KD functional data from single lab; pathway placement is indirect\",\n      \"pmids\": [\"28631286\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2016,\n      \"finding\": \"MED19 promotes breast cancer cell proliferation by suppressing CBFA2T3, which in turn increases HEB expression; MED19 knockdown upregulates CBFA2T3 and downregulates HEB, and overexpression of CBFA2T3 reverses the proliferative effect of MED19 overexpression.\",\n      \"method\": \"Lentiviral knockdown and ectopic overexpression, qRT-PCR, western blot, CCK8 and colony formation assays, epistasis rescue experiment\",\n      \"journal\": \"Breast cancer (Tokyo, Japan)\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 — single lab with genetic epistasis rescue but no direct biochemical interaction demonstrated\",\n      \"pmids\": [\"27572702\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"MED19 knockdown induces apoptosis in laryngocarcinoma HEp2 cells via activation of caspase-3, caspase-9, and Apaf-1.\",\n      \"method\": \"shRNA knockdown, caspase activity assays, western blot, flow cytometry, xenograft assay\",\n      \"journal\": \"American journal of translational research\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 — single lab, single KD approach with phenotypic but limited mechanistic depth\",\n      \"pmids\": [\"28337304\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2011,\n      \"finding\": \"MED19 knockdown in prostate cancer cells causes S-phase arrest and induces apoptosis via modulation of Bid and Caspase-7.\",\n      \"method\": \"Lentivirus-mediated shRNA knockdown, flow cytometry, western blot, colony formation, xenograft assay\",\n      \"journal\": \"BMB reports\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 — single lab, single KD method; mechanistic link to Bid/Caspase-7 not biochemically validated\",\n      \"pmids\": [\"21871180\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"LCMR1 (MED19) interacts with the chromatin-associated protein DEK in lung cancer cells; the interaction is mediated primarily by the N-terminal region of DEK, and both proteins cooperate to suppress apoptosis via the MCL-1 pathway.\",\n      \"method\": \"Yeast two-hybrid screen, co-immunoprecipitation, GST pulldown, RNAi knockdown with apoptosis readouts\",\n      \"journal\": \"Molecular medicine reports\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — reciprocal Co-IP and GST pulldown establish direct interaction; functional cooperation confirmed by RNAi epistasis\",\n      \"pmids\": [\"28765911\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2016,\n      \"finding\": \"LCMR1 (MED19) identified as a positive transcriptional regulator of Tspan8 in melanoma cells; LCMR1 modulation positively regulates endogenous Tspan8 expression with concomitant changes in cell-matrix adherence and invasion.\",\n      \"method\": \"Large-scale RNAi screen, lentiviral knockdown/overexpression, invasion and adherence assays, in vivo tumorigenicity\",\n      \"journal\": \"Oncogene\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 — functional link established by RNAi screen and KD/OE, but direct transcriptional mechanism not biochemically demonstrated\",\n      \"pmids\": [\"27375018\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"LCMR1 (MED19) diminishes RNA Pol II occupancy at promoters of HLA-encoding genes to suppress their transcription, thereby promoting immune evasion in large-cell lung cancer cells.\",\n      \"method\": \"Lentivirus-based knockdown, Pol II occupancy assay (multiple sequence-based assay), xenograft tumor model, TCGA correlation analysis\",\n      \"journal\": \"Cancers\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 — Pol II occupancy data supports the mechanistic claim but single lab and limited biochemical detail\",\n      \"pmids\": [\"38001705\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"MED19 is an integral Mediator complex subunit that stabilizes inter-module interactions (particularly anchoring the Middle module) and serves as a direct physical interface between Mediator and sequence-specific transcription factors (Hox homeodomains, GATA zinc fingers) to selectively activate developmental and signal-responsive RNA Pol II-dependent genes; additionally, MED19 localizes to the nucleolus via a C-terminal poly-lysine motif where, independently of the Mediator complex, it binds fibrillarin and rRNA to promote 2'-O-methylation and IRES-dependent translation of oncoproteins such as c-Myc.\"\n}\n```","stage2_raw":"```json\n{\n  \"mechanistic_narrative\": \"MED19 is a subunit of the Mediator complex that functions both as a structural bridge stabilizing the Middle module within the holocomplex and as a selective transcriptional coactivator that physically interfaces with sequence-specific transcription factors to control developmental and signal-responsive gene expression. In yeast, MED19 is required for stable Middle module association with the Head–Tail complex and for enhanced basal transcription, TFIIH-mediated CTD phosphorylation, and RNA Pol II recruitment [PMID:17192271]; in metazoans, MED19 directly binds Hox homeodomains and GATA zinc-finger domains through a conserved animal-specific motif to activate developmental target genes, and selectively regulates a subset of genes including Notch-responsive targets rather than serving as a global transcriptional requirement [PMID:24786462, PMID:32737196, PMID:36445897]. Independent of the Mediator complex, MED19 localizes to the nucleolus via a C-terminal poly-lysine motif, where it binds fibrillarin and rRNA to promote 2′-O-methylation and IRES-dependent translation of oncoproteins such as c-Myc [PMID:41414671].\",\n  \"teleology\": [\n    {\n      \"year\": 2006,\n      \"claim\": \"Establishing that MED19 is the structural linchpin holding the Middle module within the Mediator complex answered the fundamental question of how this multisubunit coactivator maintains its modular architecture and provided the first mechanistic explanation for why loss of a single subunit can disconnect an entire functional module.\",\n      \"evidence\": \"Purification of Mediator from Δmed19 yeast strains under varying stringency, in vitro transcription, CTD phosphorylation, and Pol II binding assays\",\n      \"pmids\": [\"17192271\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Structural contacts between MED19 and individual Middle module subunits not mapped at residue resolution\",\n        \"Whether the bridging role is conserved in metazoan Mediator was not tested\"\n      ]\n    },\n    {\n      \"year\": 2014,\n      \"claim\": \"Demonstrating that MED19 directly binds Hox homeodomains through a conserved animal-specific motif resolved how a general coactivator subunit can provide transcription-factor-specific selectivity, establishing MED19 as a dedicated activator interface for Hox-dependent developmental gene regulation.\",\n      \"evidence\": \"In vitro binding, in vivo Co-IP, clonal loss-of-function analysis, genetic modifier screen, and mutagenesis of conserved Med19 motif in Drosophila\",\n      \"pmids\": [\"24786462\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Whether the same motif also contacts non-Hox homeodomain factors was not tested\",\n        \"Structural basis of the Hox–MED19 interface remains unresolved\"\n      ]\n    },\n    {\n      \"year\": 2017,\n      \"claim\": \"Identification of DEK as a direct MED19-interacting chromatin-associated partner, and observations that MED19 knockdown modulates Wnt/β-catenin pathway output in cancer cells, expanded MED19's functional network beyond classical transcription factor contacts, though the directness of signaling pathway effects remains uncertain.\",\n      \"evidence\": \"Yeast two-hybrid, reciprocal Co-IP and GST pulldown for DEK interaction; shRNA knockdown with Wnt reporter assays in bladder cancer cells\",\n      \"pmids\": [\"28765911\", \"28631286\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Whether MED19–DEK interaction occurs on chromatin at specific loci is unknown\",\n        \"Wnt pathway effects may be indirect consequences of general Mediator transcriptional activity\",\n        \"No structural or domain-mapping data for MED19–DEK beyond N-terminal DEK region\"\n      ]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"Reports that MED19 interacts with EGFR and modulates EGFR/MEK/ERK signaling, and separately promotes autophagy-mediated chemoresistance, indicated that MED19 perturbation broadly affects oncogenic signaling outputs in breast cancer, though direct biochemical mechanisms linking MED19 to these pathways remained unclear.\",\n      \"evidence\": \"Co-IP, lentiviral knockdown/overexpression, drug sensitivity assays, and autophagy marker analysis in breast cancer cell lines\",\n      \"pmids\": [\"30583076\", \"30161287\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Whether MED19–EGFR interaction is direct or bridged through Mediator is not resolved\",\n        \"HMGB1-autophagy link is inferred from marker changes, not demonstrated biochemically\",\n        \"Single-lab findings without independent replication\"\n      ]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"Extending the transcription factor interface model, demonstration that MED19 directly binds GATA zinc-finger domains (Pannier, Serpent) and also contacts the Middle module subunit Med1 established MED19 as a multi-input hub that integrates diverse activator signals through the same Mediator subunit.\",\n      \"evidence\": \"Reciprocal in vitro binding and in vivo Co-IP, GST pulldown for Med1 interaction, RNAi-based gene expression assays in Drosophila\",\n      \"pmids\": [\"32737196\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Whether Hox and GATA factors compete or cooperate for the same MED19 surface is unknown\",\n        \"Mammalian GATA–MED19 interaction not tested\"\n      ]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"Acute endogenous MED19 degradation coupled with transcriptomics resolved the long-standing question of whether MED19 is a global or gene-selective coactivator, demonstrating that it is dispensable for the majority of transcription but specifically required for Notch-responsive and spatially regulated developmental genes.\",\n      \"evidence\": \"Auxin-inducible degradation of endogenous Med19 in Drosophila wing discs with RNA-seq and Notch pathway epistasis\",\n      \"pmids\": [\"36445897\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Mechanism by which MED19 confers Notch-pathway specificity (direct Notch ICD contact or indirect) is not established\",\n        \"Whether selective gene dependence reflects enhancer architecture or activator identity is unresolved\"\n      ]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Discovery of a Mediator-independent nucleolar function for MED19 — binding fibrillarin and rRNA via a C-terminal poly-lysine motif to promote 2′-O-methylation and IRES-dependent translation — fundamentally expanded MED19's functional repertoire beyond transcriptional coactivation into ribosome biogenesis and translational control.\",\n      \"evidence\": \"Subcellular fractionation, Co-IP with fibrillarin, RNA binding assays, poly-lysine motif mutagenesis, rRNA methylation assays, IRES-reporter translation assays in human cells\",\n      \"pmids\": [\"41414671\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Which specific rRNA 2′-O-methylation sites are MED19-dependent is not catalogued\",\n        \"Whether nucleolar MED19 functions are relevant in non-cancer developmental contexts is untested\",\n        \"Relative contribution of transcriptional vs. translational MED19 functions to oncogenesis is unresolved\"\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"A high-resolution structural model of MED19 within the intact mammalian Mediator–Pol II PIC, and the molecular basis by which MED19 distinguishes its Mediator-dependent transcriptional role from its Mediator-independent nucleolar function, remain to be established.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"No cryo-EM or crystal structure of MED19 bound to a transcription factor or to fibrillarin\",\n        \"Mechanism partitioning MED19 between Mediator and nucleolar pools is unknown\",\n        \"Whether mammalian MED19 retains the Hox/GATA-binding motif and gene-selective coactivation is not directly demonstrated\"\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0140110\", \"supporting_discovery_ids\": [0, 1, 2, 3]},\n      {\"term_id\": \"GO:0003723\", \"supporting_discovery_ids\": [4]},\n      {\"term_id\": \"GO:0060090\", \"supporting_discovery_ids\": [0, 1, 2]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005634\", \"supporting_discovery_ids\": [0, 1, 3]},\n      {\"term_id\": \"GO:0005730\", \"supporting_discovery_ids\": [4]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-74160\", \"supporting_discovery_ids\": [0, 1, 2, 3]},\n      {\"term_id\": \"R-HSA-8953854\", \"supporting_discovery_ids\": [4]},\n      {\"term_id\": \"R-HSA-392499\", \"supporting_discovery_ids\": [4]},\n      {\"term_id\": \"R-HSA-1266738\", \"supporting_discovery_ids\": [1, 2, 3]}\n    ],\n    \"complexes\": [\n      \"Mediator complex (Middle module)\"\n    ],\n    \"partners\": [\n      \"MED1\",\n      \"FBL\",\n      \"DEK\",\n      \"EGFR\"\n    ],\n    \"other_free_text\": []\n  }\n}\n```"}