ArticleMolecular and cellular endocrinology2015
The ubiquitin ligase MuRF1 regulates PPARα activity in the heart by enhancing nuclear export via monoubiquitination.
Article in Molecular and cellular endocrinology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 50 citations in OpenAlex.
- CRSP8-driven fatty acid metabolism reprogramming enhances hepatocellular carcinoma progression by inhibiting RAN-mediated PPARα nucleus-cytoplasm shuttling.Journal of experimental & clinical cancer research : CR · 2025Article
- Exploring Negative Feedback Mechanisms in the PTEN-ACE Axis: Application of Electrosorb Hydrogel-Based Gene Delivery for Intervertebral Disc Regeneration.International journal of biological sciences · 2025Article
- Knockout of the Muscle-Specific E3 Ligase MuRF1 Affects Liver Lipid Metabolism upon Dexamethasone Treatment in Mice.ACS omega · 2024Article
- Post-translational modifications in diabetic cardiomyopathy.Journal of cellular and molecular medicine · 2024Review
- Ubiquitin Proteasome System Role in Diabetes-Induced Cardiomyopathy.International journal of molecular sciences · 2023Article
- Hyodeoxycholic acid ameliorates nonalcoholic fatty liver disease by inhibiting RAN-mediated PPARα nucleus-cytoplasm shuttling.Nature communications · 2023Article
- Lysine 222 in PPAR γ1 functions as the key site of MuRF2-mediated ubiquitination modification.Scientific reports · 2023Article
- PPARα: An emerging target of metabolic syndrome, neurodegenerative and cardiovascular diseases.Frontiers in endocrinology · 2022Review
- E3 ubiquitin ligases: styles, structures and functions.Molecular biomedicine · 2021Review
- Role of UPP pathway in amelioration of diabetes-associated complications.Environmental science and pollution research international · 2021Review
- Identification of the MuRF1 Skeletal Muscle Ubiquitylome Through Quantitative Proteomics.Function (Oxford, England) · 2021Article
- MuRF1/TRIM63, Master Regulator of Muscle Mass.International journal of molecular sciences · 2020Review
- Cellular Protein Quality Control in Diabetic Cardiomyopathy: From Bench to Bedside.Frontiers in cardiovascular medicine · 2020Review
- Self-regulation of the inflammatory response by peroxisome proliferator-activated receptors.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2019Review
- Proteasome biology and therapeutics in cardiac diseases.Translational research : the journal of laboratory and clinical medicine · 2019Review
- Elucidating the Beneficial Role of PPAR Agonists in Cardiac Diseases.International journal of molecular sciences · 2018Review
- Muscle-specific regulation of right ventricular transcriptional responses to chronic hypoxia-induced hypertrophy by the muscle ring finger-1 (MuRF1) ubiquitin ligase in mice.BMC medical genetics · 2018Article
- Role of RNF20 in cancer development and progression - a comprehensive review.Bioscience reports · 2018Review
- Adverse Effects of Fenofibrate in Mice Deficient in the Protein Quality Control Regulator, CHIP.Journal of cardiovascular development and disease · 2018Article
- Hepatic PPARα function is controlled by polyubiquitination and proteasome-mediated degradation through the coordinated actions of PAQR3 and HUWE1.Hepatology (Baltimore, Md.) · 2018Article
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 2 countries.
Funding
Abstract
The transcriptional regulation of peroxisome proliferator-activated receptor (PPAR) α by post-translational modification, such as ubiquitin, has not been described. We report here for the first time an ubiquitin ligase (muscle ring finger-1/MuRF1) that inhibits fatty acid oxidation by inhibiting PPARα, but not PPARβ/δ or PPARγ in cardiomyocytes in vitro. Similarly, MuRF1 Tg+ hearts showed significant decreases in nuclear PPARα activity and acyl-carnitine intermediates, while MuRF1-/- hearts exhibited increased PPARα activity and acyl-carnitine intermediates. MuRF1 directly interacts with PPARα, mono-ubiquitinates it, and targets it for nuclear export to inhibit fatty acid oxidation in a proteasome independent manner. We then identified a previously undescribed nuclear export sequence in PPARα, along with three specific lysines (292, 310, 388) required for MuRF1's targeting of nuclear export. These studies identify the role of ubiquitination in regulating cardiac PPARα, including the ubiquitin ligase that may be responsible for this critical regulation of cardiac metabolism in heart failure.
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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.