| 2014 |
TRIM4 associates with RIG-I and targets it for K63-linked polyubiquitination, positively regulating RIG-I-mediated type I interferon induction and activation of IRF3 and NF-κB in response to viral RNA. |
Co-immunoprecipitation, overexpression and knockdown with reporter assays for IRF3, NF-κB, and IFN-β activation |
Journal of molecular cell biology |
Medium |
24755855
|
| 2015 |
TRIM4 forms cytoplasmic speckle-like structures that transiently interact with mitochondria, induces mitochondrial aggregation and increased mitochondrial ROS in the presence of H2O2, potentiates loss of mitochondrial transmembrane potential and cytochrome c release, and interacts with peroxiredoxin 1 (PRX1); this interaction is critical for H2O2-induced cell death sensitization. |
Subcellular localization imaging, overexpression/knockdown cell death assays, Co-immunoprecipitation/mass spectrometry for PRX1 interaction, mitochondrial ROS and membrane potential measurements |
Free radical biology & medicine |
Medium |
26524401
|
| 2022 |
TRIM4 interacts with SET via its RING and B-box domains (and SET's carboxyl terminus) and catalyzes K48-linked polyubiquitination of SET at K150 and K172, promoting proteasomal degradation of SET, which releases p53 and PP2A to promote ESR1 transcription and enhance ER-α expression. |
Co-immunoprecipitation, domain-mapping experiments, in vitro/cell-based ubiquitination assays with site-specific mutagenesis (K150/K172), in vivo xenograft models |
Advanced science (Weinheim, Baden-Wurttemberg, Germany) |
High |
35843886
|
| 2023 |
TRIM4 acts as an E3 ubiquitin ligase for MDA5, mediating K63-linked polyubiquitination of MDA5 to activate antiviral innate immune responses; SARS-CoV-2 Nsp8 binds both MDA5 and TRIM4 to impair this ubiquitination and suppress IFN induction. |
Co-immunoprecipitation, ubiquitination assays, reporter assays for IFN-β/NF-κB/ISRE, overexpression/knockdown functional studies |
PLoS pathogens |
Medium |
37956198
|
| 2020 |
TRIM4 interacts with TRPM8 via its SPRY domain and promotes K63-linked ubiquitination of TRPM8 at lysine K423, reducing TRPM8 cell-surface expression and negatively regulating TRPM8-mediated currents; this regulation requires the E1 enzyme UBA1. |
Co-immunoprecipitation (SPRY domain mapping), patch-clamp electrophysiology, cell-surface biotinylation, site-directed mutagenesis (K423), UBA1 knockdown |
Journal of cellular physiology |
High |
33037615
|
| 2022 |
TRIM4 inhibits PRRSV replication by ubiquitinating and degrading the viral NSP2 protein via the proteasome; TRIM4 knockdown increases virus titers and MG132 treatment blocks TRIM4-driven NSP2 degradation. |
Overexpression/siRNA knockdown viral replication assays, ubiquitination assays, proteasome inhibitor (MG132) rescue experiments |
BMC veterinary research |
Medium |
35637527
|
| 2023 |
TRIM4 uses its E3 ubiquitin ligase activity to degrade influenza A virus NP protein (within incoming vRNP and newly synthesized NP), thereby inhibiting IAV replication; ABTB1 counteracts this by interacting with TRIM4 and promoting TRIM4 degradation through the proteasome. |
Immunoprecipitation and mass spectrometry, overexpression/knockdown viral replication assays, ubiquitination assays, proteasome inhibitor rescue |
Emerging microbes & infections |
Medium |
37823597
|
| 2024 |
TRIM4 is the E3 ligase that binds and degrades TPL2 kinase via polyubiquitination at lysines K415 and K439; TRIM4 itself is stabilized by E3 ligase TRIM21, which is regulated by KRAS—mutant KRAS recruits RNF185 to degrade TRIM21, thereby destabilizing TRIM4 and stabilizing TPL2, leading to GSK3β phosphorylation/degradation and β-catenin/Wnt pathway activation. |
Proximity-dependent biotin identification (BioID), Co-immunoprecipitation, ubiquitination assays with site-specific mutagenesis (K415, K439), genetic perturbation of KRAS/TRIM21/RNF185 |
Cell reports |
High |
39178114
|
| 2024 |
TRIM4 binds hnRNPDL via its RING and B-box domains and promotes K48-linked ubiquitination and proteasomal degradation of hnRNPDL; hnRNPDL in turn binds CDKN2C isoform 2 mRNA and suppresses its expression via alternative splicing, thereby weakening sensitivity to CDK4/6 inhibitors. |
Co-immunoprecipitation, GST pull-down (domain mapping), ubiquitination assays, RIP (RNA immunoprecipitation) assay, in vivo siTRIM4 experiments |
Frontiers of medicine |
Medium |
39643799
|
| 2024 |
TRIM4 promotes ABTB1 degradation through K6, K27, K29, and K33-linked ubiquitination (mediated by the TRIM4 53–500 aa region), thereby preventing ABTB1 from ubiquitinating CDK1 (via K27-linked ubiquitination) and stabilizing CDK1 to promote G2/M progression in glioblastoma. |
Co-immunoprecipitation, ubiquitination assays with domain/lysine-specific mutagenesis, protein turnover assays, flow cytometry (cell cycle), xenograft tumor models |
International journal of biological macromolecules |
Medium |
42034143
|
| 2024 |
TRIM4 acts as an E3 ligase (atypical neddylation pathway) facilitating the neddylation and proteasomal degradation of CORO1A when bound to the small molecule Aurovertin B, functioning as a molecular glue mechanism; TRIM4-CORO1A interaction was confirmed by Co-IP, mass spectrometry, and SPPIER assay. |
Co-immunoprecipitation, mass spectrometry, SPPIER (separation of phases-based protein interaction reporter), phenotypic drug screen with multi-omics, patient-derived organoids |
Theranostics |
Medium |
39629122
|
| 2022 |
Macaca mulatta TRIM4 overexpression upregulates IFN-alpha, IFN-beta, RIG-I, MAVS, IRF3, IRF7, and antiviral gene expression, and increases IFN-β, NF-κB, and ISRE reporter activity; siRNA knockdown of TRIM4 downregulates the IFN pathway, confirming a conserved positive regulatory role in the interferon signaling pathway. |
Overexpression and siRNA knockdown with luciferase reporter assays and qRT-PCR in primate cells |
Frontiers in veterinary science |
Low |
35242838
|