ArticleToxicological sciences : an official journal of the Society of Toxicology2009
Regulation of peroxisome proliferator-activated receptor-alpha by MDM2.
Article in Toxicological sciences : an official journal of the Society of Toxicology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
What it found
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
21 citing papers in PubMed, 28 citations in OpenAlex.
- Loss of hepatic ME1 ameliorates MASLD by Suppressing peroxisomal β-Oxidation and Activating Lipophagy/Lipolysis.Journal of advanced research · 2026Article
- USP25 directly interacts with and deubiquitinates PPARα to increase PPARα stability in hepatocytes and attenuate high-fat diet-induced MASLD in mice.Cell death and differentiation · 2025Article
- Transferrin promotes fatty acid oxidation and liver tumor growth through PHD2-mediated PPARα hydroxylation in an iron-dependent manner.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Comparison of transcriptomic profiles between HFPO-DA and prototypical PPARα, PPARγ, and cytotoxic agents in wild-type and PPARα knockout mouse hepatocytes.Toxicological sciences : an official journal of the Society of Toxicology · 2024Article
- IGF2BP3 modified GLI2 transcriptionally regulates SYVN1 and facilitates sepsis liver injury through autophagy.iScience · 2024Article
- PPARα alleviates iron overload-induced ferroptosis in mouse liver.EMBO reports · 2022Article
- MDM2-Mediated Ubiquitination of RXRβ Contributes to Mitochondrial Damage and Related Inflammation in Atherosclerosis.International journal of molecular sciences · 2022Article
- PPARα: An emerging target of metabolic syndrome, neurodegenerative and cardiovascular diseases.Frontiers in endocrinology · 2022Review
- Peroxisome Proliferator-Activated Receptors (PPARs) and Oxidative Stress in Physiological Conditions and in Cancer.Antioxidants (Basel, Switzerland) · 2021Review
- E3 ubiquitin ligases: styles, structures and functions.Molecular biomedicine · 2021Review
- The roles and regulation of MDM2 and MDMX: it is not just about p53.Genes & development · 2021Review
- MDM2 and MDMX promote ferroptosis by PPARα-mediated lipid remodeling.Genes & development · 2020Article
- Hepatic PPARα function is controlled by polyubiquitination and proteasome-mediated degradation through the coordinated actions of PAQR3 and HUWE1.Hepatology (Baltimore, Md.) · 2018Article
- Functional Regulation of PPARs through Post-Translational Modifications.International journal of molecular sciences · 2018Review
- Do Mesenchymal Stem Cells Derived From Atypical Lipomatous Tumors Have Greater Differentiation Potency Than Cells From Normal Adipose Tissues?Clinical orthopaedics and related research · 2017Article
- Peroxisome Proliferator-Activated Receptor Modulation during Metabolic Diseases and Cancers: Master and Minions.PPAR research · 2016Review
- The ubiquitin ligase MuRF1 regulates PPARα activity in the heart by enhancing nuclear export via monoubiquitination.Molecular and cellular endocrinology · 2015Article
- Disruptive environmental chemicals and cellular mechanisms that confer resistance to cell death.Carcinogenesis · 2015Review
- Molecular mechanisms responsible for the reduced expression of cholesterol transporters from macrophages by low-dose endotoxin.Arteriosclerosis, thrombosis, and vascular biology · 2013Article
- The story so far: post-translational regulation of peroxisome proliferator-activated receptors by ubiquitination and SUMOylation.American journal of physiology. Heart and circulatory physiology · 2012Review
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Peroxisome proliferator-activated receptor-alpha (PPARalpha) belongs to the nuclear receptor (NR) family of transcription factors and regulates lipid and glucose metabolism. Like other NRs, the regulation of gene expression by PPARalpha depends on cofactor recruitment to the transcription complex and multiple protein-protein interactions. In this study, Murine Double Minute 2 (MDM2), an E3 ubiquitin ligase, is identified as a PPARalpha-interacting protein that regulates PPARalpha transcriptional activity. MDM2 modulated the transcriptional activity of PPARalpha and PPARbeta/delta, but not PPARgamma in reporter assays. Knockdown of MDM2 by small interfering RNA in rat hepatoma cells inhibited ligand-induced mRNA levels of several PPARalpha target genes involved in lipid metabolism. MDM2 associated with PPARalpha on target gene promoters, and this association increased in response to Wy14,643 treatment. MDM2 interacted with PPARalpha and this interaction occurred with the A/B domain of PPARalpha. Coexpression of MDM2 increased PPARalpha ubiquitination and the E3 ubiquitin ligase activity of MDM2 affected PPARalpha protein expression and transcriptional activity. MDM2 expression was decreased in response to clofibrate in wild-type (WT), but not in PPARalpha null mice, indicating a PPARalpha-dependent regulation. These studies identify a role for MDM2 in regulating PPARalpha-mediated pathways of lipid metabolism.
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What OpenQuestion holds
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.