| 2005 |
Ge-1 (EDC4) is a central component of mammalian cytoplasmic P-bodies. Its C-terminal domain (containing repeating psi(X(2-3)) motifs) is necessary and sufficient for P-body targeting. siRNA-mediated knockdown of Ge-1 results in loss of P-bodies containing Ge-1, DCP1a, and DCP2, but Ge-1-containing P-bodies persist despite knockdown of DCP2, placing Ge-1 upstream of DCP2 in P-body assembly. |
siRNA knockdown, immunofluorescence colocalization, deletion mapping, autoimmune serum identification |
RNA (New York, N.Y.) |
High |
16314453
|
| 2008 |
The crystal structure of the Drosophila Ge-1 (EDC4) C-terminal domain reveals an all alpha-helical fold related to ARM/HEAT-repeat proteins. Structure-based mutagenesis identified an invariant surface residue required for P-body localization, and conservation of critical residues suggests this fold and function are shared across the Ge-1 family. |
X-ray crystallography, structure-based mutagenesis, P-body localization assay |
RNA (New York, N.Y.) |
High |
18755833
|
| 2014 |
EDC4 serves as a scaffold for assembly of the human mRNA decapping complex, providing distinct binding sites for DCP1, DCP2, and XRN1 on its C-terminal domain. DCP2 and XRN1 bind simultaneously via short linear motifs (SLiMs). DCP1 and DCP2 form direct but weak interactions that are facilitated by EDC4. The DCP1 EVH1 domain NR-loop is critical for DCP2 activation, and this activation occurs preferentially on the EDC4 scaffold, coupling decapping with 5'-to-3' decay by XRN1. |
Mutational analysis, co-immunoprecipitation, in vivo decapping assays, binding studies |
Nucleic acids research |
High |
24510189
|
| 2011 |
Drosophila Ge-1 (dGe-1) is an essential P-body component required for P-body formation in the germline. dGe-1 partially colocalizes with oskar mRNA and is required for oskar RNP integrity. While not essential for oskar mRNA localization under normal conditions, dGe-1 becomes critical when other components (staufen, DCP1, barentsz) are limiting. |
Genetic knockouts, immunohistochemistry, biochemical fractionation, genetic epistasis with other localization factors |
PloS one |
Medium |
21655181
|
| 2012 |
EDC4 forms a complex with Coenzyme A synthase (CoAsy) and strongly inhibits the dephospho-CoA kinase activity of CoAsy in vitro. CoAsy/EDC4 complex formation is regulated by growth factors and cellular stresses. Transient overexpression of EDC4 decreases cell proliferation, and co-expression of CoAsy diminishes this effect. |
Co-immunoprecipitation, in vitro kinase activity assay, overexpression/proliferation assay |
FEBS letters |
Medium |
22982864
|
| 2014 |
CCHCR1 interacts with EDC4 (identified as the major interacting partner by co-immunoprecipitation coupled with LC-MS/MS), and this interaction targets CCHCR1 to P-bodies; the N-terminus of CCHCR1 is required for its P-body localization. |
Co-immunoprecipitation with EGFP-tagged CCHCR1, LC-MS/MS, confocal imaging, deletion mapping |
Experimental cell research |
Low |
24858563
|
| 2014 |
EDC4 (Edc4) interacts with the mTORC1 complex (identified via co-immunoprecipitation). Rapamycin treatment increases total Edc4 protein expression but decreases Edc4 interaction with mTORC1 and decreases serine phosphorylation of Edc4, suggesting mTORC1 regulates Edc4 phosphorylation and activity in mRNA decapping. |
Co-immunoprecipitation, immunoblotting, confocal colocalization, rapamycin treatment |
International journal of molecular sciences |
Low |
25514416
|
| 2016 |
A naturally occurring 26 amino acid deletion in the serine-rich linker region of Drosophila Ge-1 confers resistance to sigma virus infection. Knockdown of the susceptible allele decreases viral titre. DCP1, which interacts with Ge-1, also protects against sigma virus. Ge-1-based resistance is not dependent on the siRNA pathway. |
Transgenic fly generation with sequence modification, viral titre assay, siRNA pathway epistasis test, knockdown experiments |
PLoS pathogens |
Medium |
26799957
|
| 2018 |
EDC4 is a member of the BRCA1-BRIP1-TOPBP1 complex and plays a key role in homologous recombination by stimulating end resection at double-strand breaks. EDC4 deficiency leads to genome instability and hypersensitivity to DNA interstrand cross-linking drugs and PARP inhibitors. |
Co-immunoprecipitation (complex membership), HR assay, DNA end resection assay, drug sensitivity assay, genome instability measurement |
Nature communications |
High |
29511213
|
| 2020 |
EDC4 interacts with MARF1 endoribonuclease and impairs MARF1 activity by preventing its LOTUS domains from binding target mRNAs. This represents a non-canonical role for EDC4 as a repressor of MARF1-mediated mRNA decay, distinct from its role as an enhancer of DCP2-mediated decapping. |
Co-immunoprecipitation, transcriptome-wide MARF1 target identification, LOTUS domain RNA binding assay, mutagenesis |
eLife |
High |
32510323
|
| 2020 |
EDC4 interacts with replication protein A (RPA) by immunoprecipitation and promotes RPA phosphorylation. EDC4 knockdown enhances cisplatin-induced DNA damage and sensitivity, while EDC4 overexpression reduces DNA damage. RPA knockdown reverses the inhibitory effect of EDC4 on cisplatin-induced DNA damage, placing RPA downstream of EDC4 in this pathway. |
Co-immunoprecipitation, siRNA knockdown, overexpression, γH2AX immunofluorescence, MTT/colony assays, epistasis by double knockdown |
Hereditas |
Medium |
33054858
|
| 2023 |
Disrupting the EDC4-XRN1 interaction or altering their stoichiometry inhibits mRNA decapping and stabilizes microRNA-targeted mRNAs in a translationally repressed state. This concomitantly leads to larger P-bodies that are responsible for preventing mRNA decapping. P-bodies support cell viability and prevent stress granule formation when XRN1 is limiting. |
Interaction disruption mutants, mRNA stability assays, P-body size measurements, microRNA reporter assays, cell viability assays, stress granule imaging |
The EMBO journal |
High |
37621215
|
| 2024 |
In C. elegans, EDC-4 counteracts EDC-3 and promotes assembly of DCAP-2 (DCP2) with the GID/CTLH complex (a ubiquitin ligase involved in maternal-to-zygotic transition), linking the mRNA decapping scaffold to the ubiquitin-proteasome system during embryonic development. |
Genetic interaction studies, co-immunoprecipitation, mRNA stability assays, fluorescence microscopy in C. elegans |
Cell reports |
Medium |
39331503
|
| 2025 |
The EDC4 C-terminal domain (residues 1266-1401) is the minimal region required for P-body formation, driving phase separation and EDC4 condensation. The microprotein Nobody (NBDY) 22-41 peptide directly binds the EDC4 C-terminal domain and inhibits its self-association, selectively dissolving P-bodies without affecting the canonical mRNA decay pathway. P-body disruption activates the p53 pathway and enhances stability of associated transcripts. |
Deletion mapping, phase separation assay, direct binding assay (NBDY peptide to EDC4 CTD), P-body dissolution assay, transcriptome profiling, p53 pathway reporter |
RNA (New York, N.Y.) |
High |
40360209
|
| 2025 |
Ebola virus VP35 protein binds the EDC4 scaffold protein through the EDC4 C-terminal subdomain, with both proteins colocalizing in EBOV-infected cells. siRNA depletion of EDC4 reduces EBOV replication by inhibiting early viral RNA synthesis. |
Proximity-dependent biotinylation (BioID), co-immunoprecipitation, colocalization imaging in infected cells, siRNA knockdown with viral RNA synthesis assay |
Nature communications |
Medium |
41006235
|