| 2016 |
UBA52 encodes a ubiquitin-RPL40 fusion protein that must be cleaved to simultaneously supply both RPL40 and ubiquitin to the ribosomal complex; the RPL40 portion alone is insufficient to maintain cyclin D expression or protein synthesis, and UBA52-deficient cells show decreased protein synthesis and cell-cycle arrest rescued by UBA52 overexpression. |
Uba52 knockout mouse model, cell-cycle analysis, protein synthesis assay, overexpression rescue, ribosomal complex fractionation/co-immunoprecipitation |
Scientific reports |
High |
27829658
|
| 2018 |
UBA52 is essential for preimplantation embryo development; CRISPR/Cas9-mediated biallelic disruption of Uba52 in porcine oocytes arrests embryos at the 4-cell stage (around major zygotic genomic activation) and prevents blastocyst formation, with reduced UBA52 and proteasome protein levels and abnormal nuclear morphology. |
CRISPR/Cas9 gene editing in porcine oocytes followed by in vitro fertilization, embryo culture, immunolabeling, Western blotting |
Biology open |
High |
30135083
|
| 2019 |
RPL40 (the C-terminal product of UBA52 cleavage) functions in the ribosomal protein–MDM2–p53 pathway; the lncRNA LUCAT1 binds UBA52 (shown by chromatin isolation by RNA purification + mass spectrometry and RNA immunoprecipitation), suppressing this pathway and thereby inhibiting p53-mediated cell cycle arrest and apoptosis in colorectal cancer cells. |
ChIRP-MS, RNA immunoprecipitation, LUCAT1 knockdown with p53 pathway readouts |
Cancer science |
Medium |
30690837
|
| 2019 |
UBA52 promotes ubiquitination-dependent degradation of CCNB1 (cyclin B1) through APC11; knockdown of APC11 prevents UBA52-driven CCNB1 degradation and causes G2/M arrest even when UBA52 is overexpressed, placing UBA52 upstream of APC11 in CCNB1 proteolysis and cell cycle progression. |
Co-immunoprecipitation, shRNA/siRNA knockdown, CCNB1 overexpression/knockdown, cell cycle analysis, xenograft tumor model |
American journal of translational research |
Medium |
31814919
|
| 2022 |
UBA52 interacts with α-synuclein, HSP90, and the E3 ubiquitin ligase CHIP; the lysine-63 residue of UBA52 is required for CHIP-mediated K63-linked ubiquitylation of HSP90, as shown by in vitro ubiquitylation assay with UBA52 mutants; UBA52 also co-localizes with α-synuclein at mitochondria. |
In silico prediction, mass spectrometry, co-immunoprecipitation, in vitro ubiquitylation assay with K63 mutant, confocal co-localization, Myc-UBA52 overexpression in neuronal PD models |
Cells |
High |
36497031
|
| 2023 |
UBA52 interacts with mitochondrial outer membrane channel VDAC1 and participates in CHIP-mediated ubiquitylation of VDAC1; UBA52 overexpression in neurons preserves mitochondrial membrane potential, complex I activity, cytochrome c retention, and calcium homeostasis, inhibiting apoptotic and autophagic cell death in a Parkinson's disease model. |
Mass spectrometry, co-immunoprecipitation, in vitro ubiquitylation assay, mitochondrial membrane potential assay (JC-1), complex I activity assay, cytochrome c fractionation, Myc-UBA52 overexpression/knockdown |
ACS chemical neuroscience |
High |
36755387
|
| 2023 |
UBA52 (via its C-terminal L40/ribosomal fragment) interacts with H2A/H2AX histones and RNF168, is recruited to laser-induced DNA damage sites, and the L40 fragment inhibits RNF168-mediated H2A/H2AX ubiquitination at K13/K15 by masking the nucleosome acidic patch (E143/E144), thereby limiting 53BP1 recruitment and fine-tuning DNA repair. |
Co-immunoprecipitation, laser micro-irradiation recruitment assay, ectopic expression of ribosomal fragments, H2A/H2AX ubiquitination assay, 53BP1 recruitment assay, UBA52 knockdown |
The Journal of biological chemistry |
High |
37451480
|
| 2023 |
RPL40 (UBA52 C-terminal product) knockdown does not stabilize p53 in U2OS cells, contrasting with most ribosomal proteins; however, combined knockdown of RPS27a and RPL40 robustly induces p53 in MCF7 and LNCaP cells. Both proteins are required for rRNA production in all cell lines tested, indicating cell-type-specific roles in p53 signaling but universal roles in ribosome biogenesis. |
siRNA knockdown, Western blotting for p53 stabilization, actinomycin D treatment, rRNA production assays across multiple cell lines |
Biomolecules |
Medium |
37371478
|
| 2024 |
SMYD5 directly methyltransferases RPL40 (the ribosomal protein encoded within UBA52) at lysine 22 to produce K22me3; this modification regulates mRNA translation output and ribosome elongation fidelity (evidenced by ribosome collision upon SMYD5/K22me3 loss), and promotes oncogenic gene expression in gastric adenocarcinoma. |
Biochemical-proteomics substrate identification, in vitro methyltransferase assay with recombinant SMYD5, SMYD5 knockout cells (mass spectrometry for K22me3 loss), polysome profiling, ribosome collision assay, in vivo mouse GAC models and PDX xenografts |
Nature |
High |
39048817 39103523
|
| 2024 |
SMYD5 requires a KXY motif for recognition and trimethylation of RPL40 K22; active site mutations in recombinant SMYD5 ablate this activity; SMYD5 knockout cells lose all RPL40 K22me3 and show decreased polysome levels, confirming the enzymatic requirement for translation. |
Systematic mass spectrometry of ribosomal methylation sites, in vitro fractionated-lysate methylation assay, recombinant SMYD5 with active site mutagenesis, SMYD5 knockout, polysome profiling, recognition motif scanning |
Cell reports |
High |
40184250
|
| 2024 |
MLKL binds UBA52 under physiological conditions; loss of Mlkl prevents UBA52 cleavage and decreases free ubiquitin levels in brain; the deubiquitinase USP7 mediates UBA52 processing in a manner regulated by MLKL; reduced ubiquitin leads to decreased K63-linked polyubiquitination of BECN1 and ULK1, impairing autophagy and contributing to neurodegeneration. |
Co-immunoprecipitation (MLKL–UBA52 interaction), mlkl knockout mice (ubiquitin level measurement), USP7 deubiquitinase assay, K63 polyubiquitination analysis of BECN1/ULK1, single-nucleus RNA sequencing, cognitive behavioral tests |
Autophagy |
High |
39193909
|
| 2024 |
Knockdown of UBA52 induces autophagy through EMC6 in hepatocellular carcinoma cells, reducing HCC cell growth and metastasis both in vitro and in vivo; UBA52 thus promotes HCC proliferation and migration by suppressing EMC6-mediated autophagy. |
UBA52 knockdown/overexpression, CCK-8, colony formation, wound healing, Transwell assays, subcutaneous and metastatic xenograft mouse models, bioinformatic autophagy association analysis |
Journal of cellular and molecular medicine |
Medium |
38445807
|
| 2023 |
UBA52 drives ubiquitination and proteasomal degradation of ferroportin (Fpn) in dorsal root ganglion neurons following peripheral nerve injury; the drug hydralazine competitively binds UBA52, blocking Fpn ubiquitination, thereby reducing intracellular iron accumulation, lipid peroxidation, and neuronal ferroptosis, and accelerating axon regeneration. |
In vitro and in vivo ubiquitination assays, co-immunoprecipitation (UBA52–Fpn), competitive binding assay (hydralazine vs UBA52), ROS/iron/lipid peroxidation measurements, peripheral nerve injury mouse model with motor function readout |
Journal of pharmaceutical analysis |
High |
38352945
|
| 2018 |
UBA52 interacts with H5N1 influenza A virus PA, PA-N155, and PA-N182 proteins in chicken cells (identified by immunoprecipitation/mass spectrometry); knockdown of UBA52 significantly decreases H5N1 viral titer and attenuates proinflammatory cytokine production, establishing UBA52 as a host factor required for influenza replication. |
Immunoprecipitation followed by mass spectrometry, UBA52 knockdown, viral titer measurement, cytokine production assay |
Frontiers in microbiology |
Medium |
29867845
|
| 2002 |
The UbA52 promoter contains functional glucose-responsive E-box sequences and stress response elements (STRE); mutation of the first E-box or STRE reduces glucose-induced promoter activity; UbA52 mRNA and protein are upregulated in renal tubules of diabetic mice in proportion to blood glucose levels, and in MDCK cells under high-glucose conditions in both cell lysates and ribosomal fractions. |
Promoter deletion constructs with SEAP reporter assay, site-directed mutagenesis of E-box and STRE, in situ hybridization, immunohistochemistry, ribosomal fractionation |
The Journal of biological chemistry |
Medium |
12171997
|
| 2025 |
ROCK2 stabilizes DRP1 protein by competing with UBA52 to bind DRP1, thereby preventing UBA52-mediated ubiquitination and proteasomal degradation of DRP1; this ROCK2/UBA52/DRP1 axis drives mitochondrial dynamics and pemigatinib resistance in cholangiocarcinoma. |
Co-immunoprecipitation (ROCK2–DRP1 and UBA52–DRP1), DRP1 ubiquitination assay, ROCK2 knockdown/overexpression, DRP1 overexpression rescue experiments, in vivo xenograft model |
Cell death & disease |
Medium |
40615369
|
| 2025 |
NUDT7 interacts with UBA52 and targets it for proteasomal degradation, thereby reducing UBA52-mediated K11/K27/K48-linked polyubiquitination of the lipogenic transcription factor SREBF1, stabilizing SREBF1 and promoting lipid droplet formation to support PRRSV replication. |
Co-immunoprecipitation (NUDT7–UBA52), ubiquitination assay (K11/K27/K48 linkage-specific), NUDT7 overexpression/knockdown, SREBF1 stability assay, lipid droplet staining, viral replication assay |
International journal of biological sciences |
Medium |
41608635
|
| 2026 |
UBA52 overexpression in neurons promotes ubiquitination and degradation of the pro-apoptotic protein Daxx (identified by IP-LC/MS and Co-IP), reducing ICH-induced apoptosis and mitochondrial dysfunction; Daxx overexpression abolishes the neuroprotective effect of UBA52, placing UBA52 upstream of Daxx in the apoptosis pathway. |
IP-LC/MS, co-immunoprecipitation, AAV9-UBA52 overexpression in ICH mouse model, TUNEL assay, caspase-3/9 levels, Mitotracker/JC-1 staining, ATP measurement, Daxx rescue experiment |
Molecular neurobiology |
Medium |
41553582
|
| 2008 |
UBA52 protein is restrictedly localized to the surface of marginal cells of the stria vascularis in the cochlea of rats and mice, as determined by confocal immunocytochemistry and postembedding immunogold electron microscopy. |
Confocal microscopic immunocytochemistry on cryostat sections, postembedding immunogold cytochemistry (ultrastructural localization) |
Neuroscience |
Medium |
18448257
|
| 2025 |
Sparc binds UBA52 (confirmed by immunoprecipitation/mass spectrometry and co-immunoprecipitation) and upregulates its expression in microglia; UBA52 knockdown abolishes the anti-inflammatory and mitochondrial-protective effects of Sparc overexpression in LPS-stimulated BV2 cells, and also reverses Sparc-mediated neuroprotection in co-cultured HT-22 neurons. |
Immunoprecipitation + mass spectrometry, co-immunoprecipitation, immunofluorescence, Uba52 siRNA epistasis, cytokine ELISA, mitochondrial membrane potential assay, neurite outgrowth assay |
Frontiers in bioscience (Landmark edition) |
Medium |
40917064
|
| 2026 |
EMMPRIN downregulates UBA52 expression, reducing the free ubiquitin pool and decreasing K63-linked polyubiquitination of monocarboxylate transporter 1 (MCT1), destabilizing MCT1 and promoting global protein lactylation; this UBA52-MCT1 axis mediates EMMPRIN-driven metabolic reprogramming in metabolic-associated steatohepatitis. |
Proteomic sequencing, mass spectrometry, co-immunoprecipitation, Western blotting, EMMPRIN hepatocyte-specific KO and overexpression mouse models, K63 ubiquitination analysis |
Frontiers in pharmacology |
Medium |
41660506
|
| 2025 |
During non-segmented negative-sense virus infection, rpL40 (the ribosomal protein product of UBA52 cleavage) is recruited to a noncanonical site on the small (40S) ribosomal subunit near the mRNA entry site, forming specialized ribosomes that preferentially bind and translate viral mRNAs; this remodeling pathway is co-opted from an endogenous metabolic stress response that alters ribosome composition to promote cell survival. |
Cryo-EM or structural ribosome analysis (implied by site identification), viral infection models, preferential mRNA binding assays, metabolic stress experiments |
bioRxivpreprint |
Medium |
bio_10.1101_2025.10.24.684008
|