ArticleDiabetologia2003
A dominant negative PPARgamma mutant shows altered cofactor recruitment and inhibits adipogenesis in 3T3-L1 cells.
Article in Diabetologia, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 44 citations in OpenAlex.
- Perspective to precision medicine in scleroderma.Frontiers in immunology · 2023Article
- Artemisia scoparia promotes adipogenesis in the absence of adipogenic effectors.Obesity (Silver Spring, Md.) · 2021Article
- Tri-2-Hydroxyarachidonein Induces Cytocidal Autophagy in Pancreatic Ductal Adenocarcinoma Cancer Cell Models.Frontiers in physiology · 2021Article
- Dominant-negative and knockdown approaches to studying PPAR activity.Methods in molecular biology (Clifton, N.J.) · 2013Article
- Clinical and molecular characterization of a severe form of partial lipodystrophy expanding the phenotype of PPARγ deficiency.Journal of lipid research · 2012Article
- Pro- and antiatherogenic effects of a dominant-negative P465L mutation of peroxisome proliferator-activated receptor-γ in apolipoprotein E-Null mice.Arteriosclerosis, thrombosis, and vascular biology · 2012Article
- Electrophilic PPARγ ligands inhibit corneal fibroblast to myofibroblast differentiation in vitro: a potentially novel therapy for corneal scarring.Experimental eye research · 2012Article
- Leptin Antagonizes Peroxisome Proliferator-Activated Receptor-γ Signaling in Growth Plate Chondrocytes.PPAR research · 2012Article
- TGFβ1 Controls PPARγ Expression, Transcriptional Potential, and Activity, in Part, through Smad3 Signaling in Murine Lung Fibroblasts.PPAR research · 2012Article
- Article
- Relaxin signaling activates peroxisome proliferator-activated receptor gamma.Molecular and cellular endocrinology · 2010Article
- Altering PPARgamma ligand selectivity impairs adipogenesis by thiazolidinediones but not hormonal inducers.Obesity (Silver Spring, Md.) · 2009Article
- PPARgamma in human and mouse physiology.Biochimica et biophysica acta · 2007Review
- Non-DNA binding, dominant-negative, human PPARgamma mutations cause lipodystrophic insulin resistance.Cell metabolism · 2006Article
- Peroxisome Proliferator-Activated Receptor-gamma Promotes Adipogenic Changes in Growth Plate Chondrocytes In Vitro.PPAR research · 2006Article
- Induction of cyclin D2 in rat granulosa cells requires FSH-dependent relief from FOXO1 repression coupled with positive signals from Smad.The Journal of biological chemistry · 2005Article
- Neuronal microtubule-associated protein 2D is a dual a-kinase anchoring protein expressed in rat ovarian granulosa cells.The Journal of biological chemistry · 2004Article
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aims/hypothesisPPARgamma, a member of the nuclear hormone receptor family of transcription factors, plays a key role in adipocyte differentiation and insulin sensitivity. The aim of this study was to identify a potential dominant negative murine PPARgamma mutant and to characterize the in vitro functional properties of this mutant.
methodsIn vitro transient transfections and mammalian two-hybrid assays in TSA201 cells were used to characterize the transcriptional activity of the L466A mutant and to study the molecular interaction of transcriptional cofactors with the L466A mutant in an attempt to elucidate the mechanism of its dominant negative activity. Adenoviral constructs expressing PPARgamma wild-type (AdWT) or the L466A mutant (AdL466A) were infected into the murine 3T3-L1 cell line to study the mutant's effect on adipogenesis.
resultsThe L466A mutant alone is transcriptionally defective. However, it retains DNA binding and inhibits the ligand-dependent and -independent activity of the wild-type receptor, consistent with dominant negative properties. In mammalian two-hybrid studies, the L466A mutant does not bind nuclear receptor coactivators. However, it more avidly recruits corepressors due to enhanced binding to the corepressor ID1 domain, leading to pronounced transcriptional repression. The AdL466A mutant inhibits adipogenesis induced by either a differentiation cocktail or by thiazolidinedione ligand. AdL466A infection also blocked the upregulation of the adipocyte marker genes aP2 and adipsin.
conclusionWe conclude that the L466A PPARgamma mutant possesses potent dominant negative activity based on preferential corepressor recruitment and it inhibits adipogenesis and the expression of adipocyte-specific genes.
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