GO:0061944 negative regulation of protein K48-linked ubiquitination: Degradation Control, Genes, Functions and Research Methods
Research-grade guide for scientists and biopharma professionals
Key Takeaways
• GO:0061944 describes any process that stops, prevents or reduces K48-linked ubiquitination, the polyubiquitin chain type that targets substrate proteins for proteasomal degradation.
• Negative regulation of K48-linked ubiquitination is achieved by deubiquitinases that cleave K48 chains, by E3 ligase inhibition, or by shielding substrate lysine residues.
• This process is a central checkpoint in inflammation, cell death and stress responses, and its dysregulation contributes to cancer, cardiovascular injury and pregnancy disorders.
• Key regulators include the E3 ligases MARCH2, RNF99 and NEDD4, and deubiquitinase-containing complexes such as PSMD14-associated machinery.
• Experimental dissection relies on ubiquitination assays, proteasome inhibitors, knockout and point-mutant cell models, and CRISPR library screening.
• EDITGENE provides knockout, point-mutation, knock-in, overexpression cell models and CRISPR library screening to study K48-linked ubiquitination regulators.
Description
Protein ubiquitination is a post-translational modification in which ubiquitin is covalently attached to substrate proteins, and the topology of the ubiquitin chain determines the biological outcome. When ubiquitin monomers are linked through lysine 48 (K48), the resulting polymer typically serves as a signal for proteasomal degradation, thereby controlling the abundance of short-lived regulatory proteins. The Gene Ontology term GO:0061944, negative regulation of protein K48-linked ubiquitination, captures the processes that oppose this modification and thereby stabilize substrates that would otherwise be degraded. Understanding this term is important because the balance between K48-linked ubiquitination and its negative regulation sets the half-life of many signaling proteins, and shifting this balance can alter cell survival, immune signaling and stress responses. For example, MARCH2 limits K48-linked ubiquitination of PGAM5/MAVS/NLRP3 axis components to suppress pyroptosis during myocardial ischemia-reperfusion injury, while RNF99 promotes K48-linked ubiquitination of TAB2 to restrain TLR-mediated inflammation. Conversely, deubiquitinase-driven removal of K48 chains can stabilize oncoproteins and promote tumor stemness. Researchers therefore study GO:0061944 to identify the enzymes and adaptors that set substrate stability, and to test whether manipulating these regulators can change disease phenotypes.
negative regulation of protein K48-linked ubiquitination At A Glance
| GO ID | GO:0061944 |
|---|---|
| GO term | negative regulation of protein K48-linked ubiquitination |
| Ontology | biological_process |
| Synonym | none |
| Major function | Opposes K48-linked polyubiquitination, thereby preventing or reducing proteasomal degradation of substrate proteins |
| Definition source | QuickGO definition: Any process that stops, prevents or reduces the frequency, rate or extent of K48-linked ubiquitination, a protein ubiquitination process in which a polymer of ubiquitin, formed by linkages between lysine residues at position 48 of the ubiquitin monomers, is added to a protein; K48-linked ubiquitination targets the substrate protein for degradation |
| Related process | Protein K48-linked ubiquitination (GO:0070936) and its positive regulation |
| Example regulators | MARCH2, RNF99, NEDD4, PSMD14-associated complexes |
| Disease relevance | Cancer, myocardial ischemia-reperfusion injury, preeclampsia, intestinal ischemia/reperfusion |
What Is GO:0061944?
GO:0061944, negative regulation of protein K48-linked ubiquitination, is a biological process that stops, prevents or reduces the frequency, rate or extent of K48-linked ubiquitination. K48-linked ubiquitination is a protein ubiquitination process in which a polymer of ubiquitin, formed by linkages between lysine residues at position 48 of the ubiquitin monomers, is added to a protein, and this chain type targets the substrate protein for degradation. Negative regulation of this process therefore includes mechanisms that remove or prevent K48 chains, such as deubiquitinase-mediated chain cleavage, inhibition of the responsible E3 ligases, or protection of substrate lysine residues, all of which can increase substrate stability.
Why Is negative regulation of protein K48-linked ubiquitination Important in Cell Biology?
Negative regulation of K48-linked ubiquitination is important because it determines whether a substrate protein is degraded or preserved, and this decision controls the amplitude and duration of many signaling pathways. By opposing K48 chain formation, this process can stabilize proteins that restrain cell death, inflammation or stress responses, as shown for MARCH2 in myocardial ischemia-reperfusion injury and for RNF99 in TLR signaling. Conversely, loss of such negative regulation can accelerate degradation of protective factors and worsen disease, as seen when SOCS2-enhanced ubiquitination of SLC7A11 promotes ferroptosis and radiosensitization in hepatocellular carcinoma. Because the same principle applies across cancer, cardiovascular and pregnancy-related disorders, GO:0061944 is a focal point for mechanistic studies and therapeutic target discovery.
• Controls substrate protein half-life by opposing K48-linked polyubiquitination and proteasomal degradation.
• Shapes inflammatory signaling, as RNF99 negatively regulates TLR-mediated immune responses via K48-linked ubiquitination of TAB2.
• Modulates cell death pathways including pyroptosis and necroptosis in cardiovascular and pregnancy disorders.
• Influences ferroptosis and radiosensitivity in hepatocellular carcinoma through SOCS2-mediated ubiquitination of SLC7A11.
• Contributes to cancer stemness and immune escape when deubiquitination stabilizes oncoproteins such as c-Myc.
• Is relevant to ER stress and apoptosis in intestinal ischemia/reperfusion through HRD1-induced TMEM2 ubiquitination.
• Provides candidate therapeutic nodes in melanoma, where PSMD14-SP1-GYS1 axis components are linked to metabolism and prognosis.
• Can be studied with proteasome inhibitors, ubiquitination assays and CRISPR-engineered cell models.
• Supports drug-resistance research, as circRNA-CREIT destabilizes PKR to overcome doxorubicin resistance in TNBC.
• Offers a framework for target validation using knockout, point-mutation, knock-in and overexpression models.
What Happens During negative regulation of protein K48-linked ubiquitination?
Recognition of K48-linked chains on substrate proteins
In simple terms: The cell first needs to detect that a protein carries a K48-linked ubiquitin chain.
Negative regulation of K48-linked ubiquitination begins with recognition of the substrate and its K48-linked chain by regulatory factors. In the MARCH2 pathway, MARCH2 acts on the PGAM5/MAVS/NLRP3 axis to limit K48-linked ubiquitination and thereby inhibit pyroptosis during myocardial ischemia-reperfusion injury. Similarly, RNF99 negatively regulates TLR-mediated inflammatory immune responses via K48-linked ubiquitination of TAB2, illustrating that chain recognition and enzyme recruitment are substrate-specific. These examples show that the first step is a molecular handshake between a regulatory enzyme and a defined substrate.
Removal or prevention of K48 chain elongation
In simple terms: Once detected, the K48 chain is either trimmed or blocked from growing.
The core event of GO:0061944 is the removal or prevention of K48-linked chain elongation. Deubiquitinase-containing complexes can cleave K48 chains, while inhibitory interactions can block the responsible E3 ligases. In melanoma, the PSMD14-SP1-GYS1 axis reveals how proteasome-associated machinery and transcriptional regulators intersect with ubiquitination control. In TNBC, deacetylation-mediated c-Myc deubiquitylation facilitates mutant TP53 transcription, showing that reducing K48-linked ubiquitination can stabilize a transcription factor and drive stemness. Thus, negative regulation can occur at the level of chain editing or enzyme inhibition.
Stabilization of the substrate protein
In simple terms: If the K48 chain is removed or prevented, the protein is no longer sent to the proteasome and survives longer.
A direct consequence of negative regulation of K48-linked ubiquitination is substrate stabilization. When MARCH2 restrains K48-linked ubiquitination of the PGAM5/MAVS/NLRP3 axis, the affected proteins escape degradation and the downstream pyroptotic response is dampened. When RNF99 controls TAB2 ubiquitination, the stability of TAB2 and the intensity of TLR signaling are adjusted. This stabilization step is what connects GO:0061944 to measurable phenotypes such as reduced cell death, altered cytokine output or changed stress tolerance.
Downstream physiological and pathological outcomes
In simple terms: The stabilized proteins then change how cells behave in health and disease.
The ultimate output of negative regulation of K48-linked ubiquitination is a change in cell fate or tissue response. SOCS2-enhanced ubiquitination of SLC7A11 promotes ferroptosis and radiosensitization in hepatocellular carcinoma, demonstrating that shifting ubiquitination balance can sensitize tumors to therapy. Thrombospondin-1 regulates trophoblast necroptosis via NEDD4-mediated ubiquitination of TAK1 in preeclampsia, linking this process to pregnancy disorders. HRD1-induced TMEM2 ubiquitination promotes ER stress-mediated apoptosis through a non-canonical pathway in intestinal ischemia/reperfusion. These outcomes illustrate why GO:0061944 is studied across multiple disease contexts.
Feedback and crosstalk with stress and immune signaling
In simple terms: The process is not one-way; it feeds back into stress and immune circuits.
Negative regulation of K48-linked ubiquitination is embedded in feedback loops that tune stress and immune signaling. CircRNA-CREIT inhibits stress granule assembly and overcomes doxorubicin resistance in TNBC by destabilizing PKR, showing crosstalk between RNA-based regulation and protein stability. MARCH2-dependent control of the PGAM5/MAVS/NLRP3 axis links mitochondrial stress to innate immune activation. RNF99-dependent control of TAB2 sets the threshold for TLR responses. Together, these findings indicate that GO:0061944 operates within broader signaling networks rather than as an isolated event.
Key Genes Involved in GO:0061944 negative regulation of protein K48-linked ubiquitination
The following genes and proteins have been experimentally linked to negative regulation of K48-linked ubiquitination or to the K48-linked ubiquitination events it controls.
| Gene | Major Role | Research Relevance |
|---|---|---|
| MARCH2 | E3 ubiquitin ligase that negatively regulates K48-linked ubiquitination of the PGAM5/MAVS/NLRP3 axis | Protects against myocardial ischemia-reperfusion injury by inhibiting pyroptosis |
| RNF99 | E3 ligase that negatively regulates TLR-mediated inflammatory immune response via K48-linked ubiquitination of TAB2 | Model for inflammation control and TLR signaling |
| NEDD4 | E3 ligase mediating ubiquitination of TAK1 | Linked to trophoblast necroptosis in preeclampsia |
| SOCS2 | Promotes ubiquitination of SLC7A11 | Drives ferroptosis and radiosensitization in hepatocellular carcinoma |
| SLC7A11 | Substrate whose ubiquitination promotes ferroptosis | Therapeutic target in hepatocellular carcinoma radiosensitivity |
| TAB2 | Adaptor protein whose K48-linked ubiquitination is negatively regulated by RNF99 | Key node in TLR-mediated inflammatory immune response |
| TAK1 | Kinase whose ubiquitination is mediated by NEDD4 | Regulates trophoblast necroptosis in preeclampsia |
| PGAM5 | Component of the PGAM5/MAVS/NLRP3 axis | Mitochondrial stress and pyroptosis regulation |
| MAVS | Component of the PGAM5/MAVS/NLRP3 axis | Innate immune signaling and pyroptosis |
| NLRP3 | Component of the PGAM5/MAVS/NLRP3 axis | Inflammasome-related pyroptosis |
| PSMD14 | Proteasome-associated deubiquitinase component in the PSMD14-SP1-GYS1 axis | Melanoma prognosis and therapeutic vulnerability |
| SP1 | Transcription factor in the PSMD14-SP1-GYS1 axis | Melanoma metabolism and prognosis model |
| GYS1 | Glycogen synthase in the PSMD14-SP1-GYS1 axis | Melanoma metabolic vulnerability |
| c-Myc | Oncoprotein stabilized by deubiquitylation | TNBC stemness and immunoescape |
| PKR | Kinase destabilized by circRNA-CREIT | Stress granule assembly and doxorubicin resistance in TNBC |
| HRD1 | E3 ligase inducing TMEM2 ubiquitination | ER stress-mediated apoptosis in intestinal ischemia/reperfusion |
| TMEM2 | Substrate of HRD1-mediated ubiquitination | Non-canonical ER stress apoptosis pathway |
| CircCFL1 | Circular RNA promoting c-Myc deubiquitylation | TNBC stemness and immunoescape |
How Is negative regulation of protein K48-linked ubiquitination Regulated?
Negative regulation of K48-linked ubiquitination is itself regulated at multiple levels. Substrate availability and adaptor recruitment determine which proteins are targeted, as shown for the PGAM5/MAVS/NLRP3 axis controlled by MARCH2 and for TAB2 controlled by RNF99. The activity of E3 ligases and deubiquitinases can be modulated by interacting proteins and post-translational modifications, as illustrated by deacetylation-mediated c-Myc deubiquitylation in TNBC. Stress conditions such as ER stress and ischemia/reperfusion can shift the balance, as seen with HRD1-induced TMEM2 ubiquitination and with NEDD4-mediated TAK1 ubiquitination in preeclampsia. Metabolic state also influences this process, as indicated by the PSMD14-SP1-GYS1 axis in melanoma. Finally, non-coding RNAs can participate, as circRNA-CREIT destabilizes PKR and affects stress granule assembly and drug resistance.
negative regulation of protein K48-linked ubiquitination and Human Disease
| Gene | Disease / Biology | Potential Experimental Model |
|---|---|---|
| SOCS2 / SLC7A11 | Hepatocellular carcinoma ferroptosis and radiosensitization | Knockout and overexpression hepatocellular carcinoma cell lines with radiation treatment |
| MARCH2 | Myocardial ischemia-reperfusion injury and pyroptosis | Cardiomyocyte knockout and point-mutation models with hypoxia/reoxygenation |
| NEDD4 / TAK1 | Preeclampsia and trophoblast necroptosis | Trophoblast cell models with knock-in of ubiquitination-site mutations |
| PSMD14 / SP1 / GYS1 | Melanoma metabolism and prognosis | Melanoma cell lines with knockout or overexpression of axis components |
| HRD1 / TMEM2 | Intestinal ischemia/reperfusion and ER stress apoptosis | Intestinal epithelial cells with knockout and ER stress induction |
Cancer and therapy resistance
Negative regulation of K48-linked ubiquitination influences tumor cell survival, stemness and treatment response. SOCS2-enhanced ubiquitination of SLC7A11 promotes ferroptosis and radiosensitization in hepatocellular carcinoma, indicating that manipulating this balance can sensitize tumors to radiation. In melanoma, a metabolism-driven prognostic model and the PSMD14-SP1-GYS1 axis reveal therapeutic vulnerabilities linked to ubiquitination-related machinery. CircCFL1 promotes TNBC stemness and immunoescape via deacetylation-mediated c-Myc deubiquitylation, showing that reduced K48-linked ubiquitination can stabilize oncoproteins. CircRNA-CREIT inhibits stress granule assembly and overcomes doxorubicin resistance in TNBC by destabilizing PKR, further linking this process to chemotherapy response.
Cardiovascular and ischemia-reperfusion injury
The MARCH2 pathway protects against myocardial ischemia-reperfusion injury through negative regulation of the PGAM5/MAVS/NLRP3 axis and inhibition of pyroptosis. In intestinal ischemia/reperfusion, HRD1-induced TMEM2 ubiquitination promotes ER stress-mediated apoptosis through a non-canonical pathway. These studies show that K48-linked ubiquitination and its negative regulation are central to ischemia-reperfusion pathology in multiple organs.
Pregnancy disorders and inflammation
Thrombospondin-1 regulates trophoblast necroptosis via NEDD4-mediated ubiquitination of TAK1 in preeclampsia, connecting this process to placental pathology. RNF99 negatively regulates TLR-mediated inflammatory immune responses via K48-linked ubiquitination of TAB2, providing a mechanism for inflammatory threshold control. Together, these findings position GO:0061944 as a modulator of both sterile and infection-associated inflammation.
From negative regulation of protein K48-linked ubiquitination-Related Genes to Experimental Models
| Research Question | Suitable Model |
|---|---|
| Is the candidate gene required for negative regulation of K48-linked ubiquitination? | Knockout cell model with ubiquitination and stability assays |
| Does a specific lysine residue on the substrate mediate K48 chain formation? | Point-mutation knock-in of the acceptor lysine to arginine |
| Does a disease-associated variant alter substrate stability? | Knock-in of the patient variant with proteasome inhibitor treatment |
| Where and when does the regulator interact with the substrate? | Tagged knock-in with imaging and co-immunoprecipitation |
| Does increased regulator abundance change cell death or drug response? | Overexpression model with ferroptosis, pyroptosis or apoptosis readouts |
| Which genes modify the phenotype in a genome-wide manner? | CRISPR library screening followed by bioinformatics analysis |
How to Study the negative regulation of protein K48-linked ubiquitination Process
| Method | What It Measures | Typical Application |
|---|---|---|
| K48-linkage-specific immunoblot after immunoprecipitation | Abundance of K48-linked ubiquitin chains on a substrate | Testing whether a regulator opposes K48-linked ubiquitination |
| Cycloheximide chase | Substrate protein half-life | Confirming stabilization downstream of negative regulation |
| Proteasome inhibitor treatment | Dependence of substrate turnover on the proteasome | Validating degradation-linked phenotypes |
| Mass spectrometry ubiquitination profiling | Global ubiquitination sites and chain types | Identifying substrates and crosstalk networks |
| RNA sequencing | Transcriptional changes after perturbation | Linking ubiquitination control to gene expression programs |
| CRISPR library screening | Genes that modify a phenotype of interest | Discovering novel regulators and therapeutic targets |
| Cell death assays | Pyroptosis, necroptosis, ferroptosis or apoptosis | Phenotypic validation of ubiquitination regulators |
| Imaging of stress granules and localization | Spatial organization of RNA and protein complexes | Studying crosstalk with stress responses |
Ubiquitination and stability assays
Direct measurement of K48-linked ubiquitination typically uses immunoprecipitation of the substrate followed by immunoblotting with K48-linkage-specific antibodies, combined with proteasome inhibitors to prevent degradation. Substrate half-life can be assessed by cycloheximide chase, and chain removal can be tested by expressing candidate deubiquitinases or ligase inhibitors. These assays are the primary readout for GO:0061944 because they distinguish K48 chain abundance from total ubiquitination.
Proteomics and interactome mapping
Mass spectrometry-based proteomics can identify ubiquitination sites and interaction partners of regulators such as MARCH2, RNF99 and NEDD4. DiGly enrichment or K48-specific enrichment workflows allow global profiling of ubiquitination changes after genetic perturbation. Interactome mapping helps define which substrates are controlled by a given negative regulator and whether adaptor proteins are required.
Transcriptomic and functional genomics readouts
RNA sequencing after knockout or overexpression reveals downstream transcriptional consequences of altered K48-linked ubiquitination, as illustrated by studies of c-Myc-driven transcription in TNBC and by prognostic modeling in melanoma. CRISPR library screening can nominate modifiers of the phenotype, and bioinformatics integration of screening data with expression datasets helps prioritize candidates. These approaches connect molecular changes to pathway-level outputs.
Cell death and stress phenotyping
Because negative regulation of K48-linked ubiquitination affects pyroptosis, necroptosis, ferroptosis and apoptosis, phenotypic assays should include lactate dehydrogenase release, caspase or inflammasome readouts, lipid peroxidation measurement and ER stress markers. Imaging of stress granules and subcellular localization adds spatial information, as shown for circRNA-CREIT and PKR. Combining these readouts with ubiquitination assays provides causal evidence for the role of a regulator in GO:0061944.
How CRISPR Can Be Used to Study GO:0061944 negative regulation of protein K48-linked ubiquitination
Knockout
CRISPR knockout of candidate E3 ligases, deubiquitinases or substrates is used to test whether a gene is required for negative regulation of K48-linked ubiquitination. For example, knocking out MARCH2 or RNF99 would be expected to alter K48 chain abundance on their respective substrates and change pyroptosis or inflammatory output. Knockout models are typically validated by immunoblotting for the target protein and by K48-linkage-specific ubiquitination assays.
Point Mutation
Point mutation is used to map the specific lysine residues that accept K48-linked ubiquitin chains or the catalytic residues of regulatory enzymes. Replacing an acceptor lysine with arginine prevents chain formation and can phenocopy negative regulation, while mutating a catalytic cysteine in a deubiquitinase can abolish chain removal. These models provide residue-level causal evidence that distinguishes K48-linked events from other ubiquitination topologies.
Knock-in
Knock-in of disease-associated variants, epitope tags or fluorescent tags allows study of regulator localization, interaction and function at endogenous expression levels. Tagged knock-in enables imaging of substrate trafficking and co-immunoprecipitation under physiological conditions. Variant knock-in can reveal whether a patient mutation alters K48-linked ubiquitination and downstream phenotypes such as ferroptosis or ER stress apoptosis.
Overexpression
Overexpression of a negative regulator or its substrate is used to test sufficiency in reducing K48-linked ubiquitination and to amplify phenotypes for biochemical detection. Overexpression models are particularly useful when baseline ubiquitination is low or when the goal is to test whether increased regulator abundance protects against cell death or drug resistance. Combining overexpression with proteasome inhibitors helps distinguish stabilization from increased synthesis.
How EDITGENE Supports negative regulation of protein K48-linked ubiquitination Research
Researchers studying negative regulation of protein K48-linked ubiquitination-related genes often need to determine whether a candidate gene is causally involved in substrate stabilization, cell death or disease phenotypes. Establishing causality requires clean genetic models in which the candidate regulator, substrate or ubiquitination site is precisely altered, followed by quantitative readouts of K48 chain abundance and downstream biology. EDITGENE provides the engineered cell models and screening services needed to move from correlation to mechanism.
Contact EDITGENE today to design your custom CRISPR model for negative regulation of protein K48-linked ubiquitination research.
Frequently Asked Questions About negative regulation of protein K48-linked ubiquitination
What is negative regulation of protein K48-linked ubiquitination?
It is the biological process, annotated as GO:0061944, that stops, prevents or reduces K48-linked ubiquitination, the polyubiquitin chain type that targets proteins for proteasomal degradation.
What is the GO ID for negative regulation of protein K48-linked ubiquitination?
The GO ID is GO:0061944, and it belongs to the biological_process ontology.
What genes are involved in negative regulation of protein K48-linked ubiquitination?
Reported regulators and related genes include MARCH2, RNF99, NEDD4, SOCS2, PSMD14, SP1, GYS1, c-Myc, PKR, HRD1 and TMEM2.
Why is K48-linked ubiquitination associated with protein degradation?
K48-linked polyubiquitin chains are a canonical signal that delivers substrate proteins to the proteasome for degradation.
How does MARCH2 regulate K48-linked ubiquitination?
MARCH2 negatively regulates the PGAM5/MAVS/NLRP3 axis through K48-linked ubiquitination control, which inhibits pyroptosis and protects against myocardial ischemia-reperfusion injury.
How does RNF99 control inflammation?
RNF99 negatively regulates TLR-mediated inflammatory immune responses via K48-linked ubiquitination of TAB2.
Is negative regulation of K48-linked ubiquitination important in cancer?
Yes, it affects ferroptosis and radiosensitization in hepatocellular carcinoma, melanoma metabolism and prognosis, and TNBC stemness and drug resistance.
What methods are used to study K48-linked ubiquitination?
Common methods include K48-linkage-specific immunoblotting after immunoprecipitation, cycloheximide chase, proteasome inhibitor treatment, mass spectrometry, RNA sequencing and CRISPR screening.
Can CRISPR be used to study negative regulation of K48-linked ubiquitination?
Yes, knockout, point mutation, knock-in and overexpression CRISPR models are used to test causality and to map ubiquitination sites.
What diseases are linked to defects in this process?
Reported links include hepatocellular carcinoma, melanoma, TNBC, myocardial ischemia-reperfusion injury, intestinal ischemia/reperfusion and preeclampsia.
Conclusion
GO:0061944, negative regulation of protein K48-linked ubiquitination, defines the processes that oppose the degradation-linked K48 polyubiquitin signal and thereby stabilize key regulatory proteins. Experimental evidence across cancer, cardiovascular injury, intestinal ischemia/reperfusion and pregnancy disorders shows that this process controls cell death, inflammation and therapy response. Because the balance between K48-linked ubiquitination and its negative regulation is decisive for substrate fate, precise genetic models are essential for mechanistic and translational studies. EDITGENE supports this work with knockout, point-mutation, knock-in, overexpression cell models and CRISPR library screening combined with bioinformatics analysis.
References
- 1. Chen Q et al.. 2023. SOCS2-enhanced ubiquitination of SLC7A11 promotes ferroptosis and radiosensitization in hepatocellular carcinoma.. Cell Death Differ 30(1):137-151 PMID: 35995846
- 2. Liu S et al.. 2024. The E3 ubiquitin ligase MARCH2 protects against myocardial ischemia-reperfusion injury through inhibiting pyroptosis via negative regulation of PGAM5/MAVS/NLRP3 axis.. Cell Discov 10(1):24 PMID: 38409220
- 3. Hu H et al.. 2024. Thrombospondin-1 Regulates Trophoblast Necroptosis via NEDD4-Mediated Ubiquitination of TAK1 in Preeclampsia.. Adv Sci (Weinh) 11(21):e2309002 PMID: 38569496
- 4. Xie J et al.. 2026. A Metabolism-Driven Prognostic Model and PSMD14-SP1-GYS1 Axis Reveal Therapeutic Vulnerabilities in Melanoma.. J Invest Dermatol 146(4):1074-1088.e5 PMID: 40967300
- 5. Zhao X et al.. 2024. HRD1-induced TMEM2 ubiquitination promotes ER stress-mediated apoptosis through a non-canonical pathway in intestinal ischemia/reperfusion.. Cell Death Dis 15(2):154 PMID: 38378757
- 6. Wang Z et al.. 2024. CircCFL1 Promotes TNBC Stemness and Immunoescape via Deacetylation-Mediated c-Myc Deubiquitylation to Facilitate Mutant TP53 Transcription.. Adv Sci (Weinh) 11(34):e2404628 PMID: 38981022
- 7. Zhang J et al.. 2023. E3 ligase RNF99 negatively regulates TLR-mediated inflammatory immune response via K48-linked ubiquitination of TAB2.. Cell Death Differ 30(4):966-978 PMID: 36681779
- 8. Wang X et al.. 2022. CircRNA-CREIT inhibits stress granule assembly and overcomes doxorubicin resistance in TNBC by destabilizing PKR.. J Hematol Oncol 15(1):122 PMID: 36038948
