ArticleCell death and differentiation2014
Suppression of PPARγ through MKRN1-mediated ubiquitination and degradation prevents adipocyte differentiation.
Article in Cell death and differentiation, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 68 papers.
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Who cites it
68 citing papers in PubMed, 97 citations in OpenAlex.
- Post-translational modification-regulating biomaterials for regeneration.Bioactive materials · 2026Review
- The Ageing Adipose Paradox: Implications for Metabolic Health.Diabetes, obesity & metabolism · 2026Review
- Mycobacterium tuberculosis IDH-PPARγ interaction suppresses GPX4 to drive macrophage ferroptosis and sustain persistent infection.Nature communications · 2026Article
- TRIM28 orchestrates SUMO-ubiquitin crosstalk to stabilize PPARG and drive bladder cancer progression.Cell death & disease · 2026Article
- Caspase-6 Controls Lipid and Energy Metabolism in Diet-Induced Obesity.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Mitochondrial retrograde signal through GCN5L1 transition-mediated PPARγ stabilization promotes MASLD development.JCI insight · 2026Article
- Mixtures ofToxics · 2025Article
- MKRN1 degrades AGC1 to trigger chemotherapy resistance of colorectal Cancer.Molecular medicine (Cambridge, Mass.) · 2025Article
- The deubiquitinase USP28 maintains the expression of PPARγ and its inactivation protects mice from diet-induced MASH and hepatocarcinoma.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- The emerging role of E3 ubiquitin ligases and deubiquitinases in metabolic dysfunction-associated steatotic liver disease.Journal of translational medicine · 2025Review
- Preventive Effect of Oleanolic Acid on Ulcerative Colitis Caused by Dextran Sulfate Sodium via a PPARγ-Involved Mechanism in Mice.Drug design, development and therapy · 2025Article
- Oxidative Stress and the Nrf2/PPARγ Axis in the Endometrium: Insights into Female Fertility.Cells · 2024Review
- Microglial Pdcd4 deficiency mitigates neuroinflammation-associated depression via facilitating Daxx mediated PPARγ/IL-10 signaling.Journal of neuroinflammation · 2024Article
- RNA-Seq Analysis Reveals the Molecular Mechanisms Regulating the Development of Different Adipose Tissues in Broiler Chicks.Animals : an open access journal from MDPI · 2024Article
- Regulation of PPARγ2 Stability and Activity by SHP-1.Molecular and cellular biology · 2024Article
- Obesity-Linked PPARγ Ser273 Phosphorylation Promotes Beneficial Effects on the Liver, despite Reduced Insulin Sensitivity in Mice.Biomolecules · 2023Article
- Lysine 222 in PPAR γ1 functions as the key site of MuRF2-mediated ubiquitination modification.Scientific reports · 2023Article
- Roles of Protein Post-Translational Modifications During Adipocyte Senescence.International journal of biological sciences · 2023Review
- The Potential Roles of Post-Translational Modifications of PPARγ in Treating Diabetes.Biomolecules · 2022Review
- Lineage-selective super enhancers mediate core regulatory circuitry during adipogenic and osteogenic differentiation of human mesenchymal stem cells.Cell death & disease · 2022Article
8 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The central regulator of adipogenesis, PPARγ, is a nuclear receptor that is linked to obesity and metabolic diseases. Here we report that MKRN1 is an E3 ligase of PPARγ that induces its ubiquitination, followed by proteasome-dependent degradation. Furthermore, we identified two lysine sites at 184 and 185 that appear to be targeted for ubiquitination by MKRN1. Stable overexpression of MKRN1 reduced PPARγ protein levels and suppressed adipocyte differentiation in 3T3-L1 and C3H10T1/2 cells. In contrast, MKRN1 depletion stimulated adipocyte differentiation in these cells. Finally, MKRN1 knockout MEFs showed an increased capacity for adipocyte differentiation compared with wild-type MEFs, with a concomitant increase of PPARγ and adipogenic markers. Together, these data indicate that MKRN1 is an elusive PPARγ E3 ligase that targets PPARγ for proteasomal degradation by ubiquitin-dependent pathways, and further depict MKRN1 as a novel target for diseases involving PPARγ.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.