ArticleJCI insight2020
Increased SUMO-activating enzyme SAE1/UBA2 promotes glycolysis and pathogenic behavior of rheumatoid fibroblast-like synoviocytes.
Article in JCI insight, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 52 citations in OpenAlex.
- UBA2: the gatekeeper of the sumoylation pathway and its multifaceted roles in human diseases and therapeutic prospects.Clinical and experimental medicine · 2026Review
- Targeting post-translational modifications: novel insights into bone metabolic diseases.Journal of advanced research · 2026Review
- MSMP promotes an aberrant phenotype of fibroblast-like synoviocytes in rheumatoid arthritis by blocking autophagy via the RUNX1/GPR137B axis.Arthritis research & therapy · 2026Article
- Immunometabolic dysregulation in autoimmune rheumatic diseases: the central role of glycolytic reprogramming in pathogenesis and traditional Chinese medicine therapy.Frontiers in immunology · 2026Review
- USP5 promotes glycolysis of fibroblast-like synoviocytes by stabilizing the METTL14/mCell death discovery · 2025Article
- Exploring the ubiquitination regulatory network: opening new perspectives for rheumatoid arthritis therapy.Annals of medicine · 2025Review
- Nuclear PKM2: a signal receiver, a gene programmer, and a metabolic modulator.Journal of biomedical science · 2025Review
- Integrating Network Pharmacology and Experimental Validation to Explore the Effect and Mechanism ofPharmaceuticals (Basel, Switzerland) · 2025Article
- Unveiling the Therapeutic Potential: Targeting Fibroblast-like Synoviocytes in Rheumatoid Arthritis.Expert reviews in molecular medicine · 2025Review
- Ubiquitin-like Proteins in Autoimmune Diseases: Current Evidence and Therapeutic Opportunities.Immune network · 2025Review
- Crossing the metabolic homeostasis divide: panoramic decoding of therapeutic targets for metabolic-inflammatory crosstalk in rheumatoid arthritis.Frontiers in immunology · 2025Review
- Regulation of the immune microenvironment by SUMO in diabetes mellitus.Frontiers in immunology · 2025Review
- Metabolic reprogramming: the central mechanism driving inflammatory polarization in rheumatoid arthritis and the regulatory role of traditional Chinese medicine.Frontiers in immunology · 2025Review
- Integrated multi-omics for potential biomarkers and molecular mechanism of persistent inflammatory refractory rheumatoid arthritis.Frontiers in immunology · 2025Article
- CHAC1 blockade suppresses progression of lung adenocarcinoma by interfering with glucose metabolism via hijacking PKM2 nuclear translocation.Cell death & disease · 2024Article
- Targeting pyruvate kinase M2 for the treatment of kidney disease.Frontiers in pharmacology · 2024Review
- GLUT-1/PKM2 loop dysregulation in patients with non-ST-segment elevation myocardial infarction promotes metainflammation.Cardiovascular research · 2023Article
- SMOC2 promotes aggressive behavior of fibroblast-like synoviocytes in rheumatoid arthritis through transcriptional and post-transcriptional regulating MYO1C.Cell death & disease · 2022Article
- Review
- Mitochondrial Dysfunction and Oxidative Stress in Rheumatoid Arthritis.Antioxidants (Basel, Switzerland) · 2022Review
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Authors and funding
14 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Fibroblast-like synoviocytes (FLSs) are critical to joint inflammation and destruction in rheumatoid arthritis (RA). Increased glycolysis in RA FLSs contributes to persistent joint damage. SUMOylation, a posttranslational modification of proteins, plays an important role in initiation and development of many diseases. However, the role of small ubiquitin-like modifier-activating (SUMO-activating) enzyme 1 (SAE1)/ubiquitin like modifier activating enzyme 2 (UBA2) in regulating the pathogenic FLS behaviors is unknown. Here, we found an increased expression of SAE1 and UBA2 in FLSs and synovial tissues from patients with RA. SAE1 or UBA2 knockdown by siRNA and treatment with GA, an inhibitor of SAE1/UBA2-mediated SUMOylation, resulted in reduced glycolysis, aggressive phenotype, and inflammation. SAE1/UBA2-mediated SUMOylation of pyruvate kinase M2 (PKM2) promoted its phosphorylation and nuclear translocation and decreased PK activity. Moreover, inhibition of PKM2 phosphorylation increased PK activity and suppressed glycolysis, aggressive phenotype, and inflammation. We further demonstrated that STAT5A mediated SUMOylated PKM2-induced glycolysis and biological behaviors. Interestingly, GA treatment attenuated the severity of arthritis in mice with collagen-induced arthritis and human TNF-α transgenic mice. These findings suggest that an increase in synovial SAE1/UBA2 may contribute to synovial glycolysis and joint inflammation in RA and that targeting SAE1/UBA2 may have therapeutic potential in patients with RA.
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