| 2019 |
RNF34 binds to MAVS in the mitochondrial compartment after viral infection and catalyzes K27-/K29-linked ubiquitination of MAVS at Lys 297, 311, 348, and 362, serving as a recognition signal for NDP52-dependent autophagic degradation. RNF34 also initiates a K63- to K27-linked ubiquitination transition on MAVS primarily at Lys 311, facilitating autophagic degradation upon RIG-I stimulation and negatively regulating RLR-mediated antiviral immunity. |
Co-immunoprecipitation, ubiquitination assays with linkage-specific antibodies, site-directed mutagenesis of MAVS lysine residues, NDP52 interaction studies, autophagy flux assays |
The EMBO journal |
High |
31304625
|
| 2011 |
RNF34 is a nuclear E3 ubiquitin ligase that interacts with and ubiquitinates PGC-1α to promote its proteasomal degradation via its C-terminal half, independently of the previously identified N-terminal phosphodegron motif. Knockdown of RNF34 in brown fat cells increases PGC-1α protein level, UCP1 expression, and oxygen consumption; cold exposure and β3-adrenergic signaling suppress RNF34 expression. |
Luciferase-based overexpression screen, co-immunoprecipitation, ubiquitination assay, RNF34 knockdown and overexpression with ligase-dead mutant control, oxygen consumption measurement |
Molecular and cellular biology |
High |
22064484
|
| 2014 |
RNF34 interacts with the large intracellular loop of the GABAA receptor γ2 subunit and ubiquitinates it, promoting GABAAR degradation via both lysosomal and proteasomal pathways. Mutating several lysines in the γ2 intracellular loop to arginines renders the subunit resistant to RNF34-induced degradation. RNF34 overexpression in hippocampal neurons decreases γ2 GABAAR cluster density and GABAergic innervation, while RNF34 knockdown increases them. |
Yeast two-hybrid, in vitro pulldown, co-immunoprecipitation from brain extracts, co-transfection in HEK293 cells, ubiquitination assay, site-directed mutagenesis of γ2 lysines, leupeptin/MG132 inhibitor experiments, immunofluorescence of hippocampal neurons, electron microscopy immunocytochemistry, shRNA knockdown |
The Journal of biological chemistry |
High |
25193658
|
| 2014 |
RNF34 interacts with NOD1 and promotes its ubiquitination and degradation, negatively regulating NOD1-dependent NF-κB activation. RNF34 overexpression inhibits NOD1-dependent NF-κB activation, while RNF34 siRNA knockdown increases NF-κB activation upon NOD1 overexpression or ligand stimulation. |
Yeast two-hybrid screening, co-immunoprecipitation, GST pulldown, western blotting for NOD1 stability and ubiquitination, NF-κB reporter assay, siRNA knockdown |
Cellular physiology and biochemistry |
Medium |
25012219
|
| 2019 |
RNF34 interacts with PGC-1α in neurons and targets it for ubiquitin-dependent proteasomal degradation, thereby potentiating mitochondrial dysfunction-mediated oxidative stress after intracerebral hemorrhage. RNF34 overexpression exacerbated ICH-induced decreases in PGC-1α, UCP2, and MnSOD expression. |
Co-immunoprecipitation, ubiquitination assay, RNF34 transgenic mouse model, measurement of ROS, mitochondrial ROS, ATP production, western blotting |
Scientific reports |
Medium |
31704983
|
| 2022 |
RNF34 participates in peripheral quality control of CFTR by directly recognizing CFTR NBD1 and selectively promoting ubiquitination of unfolded proteins. RNF34 localizes to cytoplasm and endosomes. Simultaneous ablation of RNF34 and RFFL dramatically increases functional plasma membrane expression of ∆F508-CFTR and inhibits its degradation in post-Golgi compartments. |
In vitro ubiquitination assay with recombinant proteins, subcellular localization by fluorescence microscopy, RNF34 ablation (siRNA/knockout), CFTR-NLuc degradation assay, flow cytometry for PM density |
Frontiers in molecular biosciences |
Medium |
35355508
|
| 2021 |
RNF34 interacts with p22phox in vascular smooth muscle cells and promotes its ubiquitin-mediated proteasomal degradation. Loss of RNF34 in smooth muscle cells increases p22phox protein stability, enhancing p22phox/p47phox and p22phox/NOX2 binding, NADPH oxidase complex formation, and ROS generation, leading to cerebrovascular remodeling and hypertension. |
Immunoprecipitation, ubiquitination assay, conditional (SMC-specific) RNF34 knockout mice, ROS measurement, NADPH oxidase activity assay, p22phox knockdown rescue experiment |
Neurobiology of disease |
Medium |
34015492
|
| 2021 |
RNF34 is recruited to interact with TAX1BP1 and facilitates autophagic degradation of MAVS through K27-linked polyubiquitination. This interaction suppresses NLRP3 mitochondrial localization and inflammasome activation in cardiomyocytes under ischemic stress. Knockdown of RNF34 nullified TAX1BP1-mediated protection against MAVS mitochondrial accumulation and NLRP3 inflammasome activation. |
Co-immunoprecipitation, ubiquitination assay, siRNA knockdown of RNF34, adenoviral overexpression of TAX1BP1, mitochondrial membrane potential measurement |
Science bulletin |
Medium |
36654301
|
| 2018 |
Drosophila RNF34 (dRNF34) ubiquitinates Drosophila PGC-1 (dPGC-1) and promotes its degradation. Muscle-specific knockdown of dRNF34 in vivo promotes mitochondrial biogenesis, improves locomotor performance, and counteracts high-fat-diet-induced triglyceride accumulation; these effects are reversed by co-knockdown of dPGC-1, establishing genetic epistasis. |
Immunoprecipitation and western blotting in HEK293T cells, in vivo RNAi using muscle-specific Gal4 driver, mitochondrial biogenesis assays, climbing/exercise assays, triglyceride measurement, epistasis by double knockdown |
Acta biochimica et biophysica Sinica |
Medium |
30247505
|
| 2023 |
RNF34 forms a 'ZRR' complex with ZFYVE21 (a Rab5 effector) and Rubicon on early endosomes. Within this complex, RNF34 ubiquitinates and degradatively removes Flightless I (FliI) — an inhibitory pseudosubstrate of caspase-1 — from the signaling endosome, thereby increasing endosome-associated caspase-1 available for activation and promoting NLRP3 inflammasome activity in endothelial cells. |
Proteomics/AP-MS of FACS-sorted inflammasomes, co-immunoprecipitation, endosomal fractionation, RNF34 functional studies in endothelial cells, in vivo mouse models (three models), human tissue validation |
Nature communications |
High |
37225719
|