| 2006 |
Med19 (Rox3) in S. cerevisiae is required for stable association of the Middle module with the Mediator complex; deletion of Med19 allows the Middle module to dissociate under stringent conditions, leaving a Head-Tail complex. The Med19-deficient Mediator lacking the Middle module cannot facilitate activated transcription, cannot stimulate enhanced basal transcription, cannot enhance TFIIH phosphorylation of the RNA Pol II CTD, and cannot bind RNA Pol II/CTD, establishing Med19 as a structural linchpin that couples the Middle module to transcriptional activation. |
Biochemical purification of Mediator from Δmed19 yeast strains under mild and stringent conditions; in vitro transcription assays; CTD phosphorylation assays; RNA Pol II binding assays |
The Journal of biological chemistry |
High |
17192271
|
| 2014 |
Drosophila Med19 directly binds Hox transcription factor homeodomains both in vitro and in vivo through a conserved animal-specific motif. Loss-of-function Med19 mutations act as dose-sensitive genetic modifiers that synergistically alter Hox-directed developmental outcomes, and clonal analysis shows Med19 is required for Hox-dependent target gene activation, establishing Med19 as a direct molecular link between Hox homeodomains and the RNA Pol II machinery. |
In vitro binding assays (direct homeodomain-Med19 binding), in vivo co-immunoprecipitation, loss-of-function genetics and clonal analysis, targeted mutagenesis of the conserved motif, reporter gene assays for Ultrabithorax target activation |
PLoS genetics |
High |
24786462
|
| 2020 |
Drosophila Med19 physically interacts directly with GATA transcription factors (Pannier and Serpent) through their conserved C-zinc finger domains both in vivo and in vitro, and is required for GATA-dependent gene expression. Med19 also directly interacts with Med1 by GST pulldown, identifying Med19/Med1 as a composite GATA TF interface within the Mediator middle module. |
Co-immunoprecipitation in vivo, in vitro binding assays, GST pulldown (Med19-Med1 interaction), loss-of-function genetics, reporter gene assays in cellulo |
The Journal of biological chemistry |
High |
32737196
|
| 2017 |
LCMR1 (MED19) physically interacts with the DEK protein, with the interaction mediated primarily by the N-terminal region of DEK. Both proteins cooperate to suppress apoptosis in lung cancer cells via the MCL-1 pathway, as demonstrated by yeast two-hybrid screening, co-immunoprecipitation, and GST pulldown. |
Yeast two-hybrid screen of lung cancer cDNA library, co-immunoprecipitation (in vivo), GST pulldown (in vitro), RNA interference knockdown with apoptosis readout |
Molecular medicine reports |
Medium |
28765911
|
| 2018 |
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; the oncogenic effect of Med19 is mediated through EGFR signaling, as demonstrated by co-immunoprecipitation and rescue experiments. |
Co-immunoprecipitation (Med19-EGFR), shRNA knockdown and overexpression, EGFR pathway inhibitor rescue, in vitro and in vivo functional assays |
Cancer letters |
Medium |
30583076
|
| 2018 |
Med19 promotes autophagy and chemoresistance in breast cancer cells through the HMGB1 pathway; lentivirus-mediated Med19 inhibition suppressed LC3-II/LC3-I ratio, Atg3, Atg5 expression and LC3 puncta formation, and increased sensitivity to ADM, DDP, and TAX. The autophagy-promoting effect of Med19 was mediated via HMGB1 signaling. |
Lentivirus shRNA knockdown, autophagy markers (LC3-II/I ratio, p62, RFP-LC3 dots), Western blot for HMGB1 pathway components, cell viability assays with chemotherapeutic agents |
Journal of cellular biochemistry |
Medium |
30161287
|
| 2016 |
Med19 promotes breast cancer cell proliferation by suppressing CBFA2T3 expression, which in turn allows HEB expression; Med19 knockdown upregulates CBFA2T3 and downregulates HEB, while ectopic CBFA2T3 overexpression reverses the proliferative effect of Med19 overexpression, placing CBFA2T3/HEB downstream of Med19 in a regulatory axis. |
Lentivirus-mediated Med19 inhibition and overexpression, ectopic CBFA2T3 expression rescue, RT-PCR and Western blot for CBFA2T3 and HEB, cell proliferation and colony formation assays, correlation analysis in patient tissues |
Breast cancer (Tokyo, Japan) |
Medium |
27572702
|
| 2017 |
Med19 knockdown in bladder cancer cells decreases Wnt/β-catenin pathway activity (measured by TOP/FOPflash reporter), downregulates Wnt2, β-catenin, Cyclin-D1, and MMP-9, and elevates GSK3β and E-cadherin, positioning Med19 as an upstream regulator of the Wnt/β-catenin pathway in bladder cancer proliferation and migration. |
shRNA knockdown, TOP/FOPflash Wnt reporter assay, Western blot, RT-PCR, in vitro proliferation and migration assays, in vivo xenograft |
Journal of cellular and molecular medicine |
Medium |
28631286
|
| 2021 |
In a large-scale RNAi screen, LCMR1 (MED19) was identified as a transcriptional activator of Tspan8 in melanoma cells; LCMR1 modulation positively regulated endogenous Tspan8 expression with concomitant changes in melanoma cell-matrix adherence and invasion, establishing Tspan8 as the first known LCMR1 transcriptional target linking MED19 to a specific invasive phenotype. |
Large-scale RNAi screen for Tspan8 regulators, shRNA knockdown of LCMR1, qRT-PCR and Western blot for Tspan8, in vitro invasion and adhesion assays, in vivo tumorigenicity |
Oncogene |
Medium |
27375018
|
| 2016 |
FOXD3 acts as a transcription factor that activates miR-214 expression (validated by ChIP assay), and miR-214 directly targets MED19 3'UTR (validated by dual-luciferase reporter assay) to suppress MED19 translation; miR-214 mediates the inhibitory effect of FOXD3 on colorectal cancer proliferation, invasion and metastasis through MED19 suppression. |
ChIP assay (FOXD3 binding to miR-214 promoter), dual-luciferase reporter assay (miR-214 targeting MED19 3'UTR), bisulfite sequencing, in vitro and in vivo functional assays, Western blot and RT-PCR |
British journal of cancer |
Medium |
27811858
|
| 2020 |
SP1 activates LINC00339 expression by binding its promoter (binding validated by luciferase assay); LINC00339 acts as a miR-378a-3p sponge (validated by luciferase and RNA pulldown assay); miR-378a-3p directly targets MED19 3'UTR (validated by luciferase assay), thereby establishing a SP1/LINC00339/miR-378a-3p/MED19 regulatory axis controlling CRC proliferation and Wnt/β-catenin signaling. |
Dual-luciferase reporter assay, RNA pulldown assay, gain- and loss-of-function experiments, Western blot, in vivo tumor growth assay |
OncoTargets and therapy |
Medium |
33235461
|
| 2022 |
In Drosophila wing imaginal discs, auxin-inducible degradation of endogenous Med19 followed by RNA-seq shows that Med19 is not globally required for mRNA transcription but specifically regulates less than one quarter of expressed genes; Med19-dependent genes are enriched for spatially-regulated developmental genes while constitutively expressed genes are largely unaffected. Med19 is required for Notch-responsive target gene expression (wingless and E(spl)-C genes), suggesting a specific role as a transcriptional effector of developmental signaling pathways. |
Auxin-inducible degron system for endogenous Med19 degradation in vivo, RNA-seq, differential gene expression analysis, cross-referencing with developmental gene expression databases, in vivo reporter assays for Notch target genes |
PloS one |
High |
36445897
|
| 2025 |
MED19 localizes to the nucleolus independently of the Mediator complex; this nucleolar targeting is mediated by a conserved poly-lysine motif at the MED19 C-terminus. In the nucleolus, MED19 binds ribosomal RNA and fibrillarin (FBL), a catalytic component of the 2'-O-methyltransferase complex, and facilitates rRNA processing and 2'-O-methylation. This promotes IRES-dependent translation efficiency for onco-promoting genes including c-Myc. |
Subcellular fractionation and imaging for nucleolar localization, C-terminal poly-lysine motif mutagenesis, co-immunoprecipitation with FBL, rRNA binding assays, rRNA 2'-O-methylation assays, IRES-reporter translation assays, Western blot for c-Myc |
Nucleic acids research |
High |
41414671
|
| 2023 |
LCMR1 (MED19) reduces RNA Pol II occupancy at the promoters of HLA-encoding genes, suppressing their transcription; lentivirus-based knockdown of LCMR1 de-repressed HLA gene expression and inhibited large-cell lung cancer proliferation, migration, and invasion in vitro and reduced xenograft tumor growth in vivo. |
Lentivirus-based knockdown, RNA Pol II occupancy assay at HLA gene promoters (multiple sequence-based assay), RT-PCR/Western blot for HLA gene expression, xenograft mouse model, proliferation/migration/invasion assays |
Cancers |
Medium |
38001705
|
| 2026 |
MBD2 silences the SFRP1 tumor suppressor in CRC by blocking MED19 binding to the methylated SFRP1 promoter; when MBD2 is inhibited (genetically or by KCC07), MED19 can bind the SFRP1 promoter, which is required for RNA Pol II CTD-S7 phosphorylation and productive transcription of SFRP1, thereby activating Wnt pathway antagonism. |
siRNA and small molecule (KCC07) inhibition of MBD2, ChIP for MED19 binding at SFRP1 promoter, RNA Pol II CTD-S7 phosphorylation assays, SFRP1/β-catenin Western blot, Wnt reporter assay, in vivo tumor growth assay |
Cancer biology & therapy |
Medium |
42084802
|
| 2011 |
shRNA-mediated knockdown of MED19 in prostate cancer cells (PC-3 and DU145) induces S-phase arrest and apoptosis via modulation of Bid and Caspase 7, reducing cell proliferation and tumor growth in nude mouse xenografts. |
Lentivirus shRNA knockdown, flow cytometry (cell cycle), apoptosis assays, Western blot for Bid and Caspase 7, in vivo xenograft |
BMB reports |
Low |
21871180
|
| 2017 |
Med19 knockdown in laryngocarcinoma HEp2 cells induces apoptosis via activation of caspases 3, 9, and Apaf-1, identifying an Apaf-1-dependent intrinsic apoptosis pathway downstream of Med19 inhibition. |
shRNA knockdown, Western blot and activity assays for caspase-3, caspase-9, Apaf-1, cell growth and migration assays, in vivo xenograft |
American journal of translational research |
Low |
28337304
|