ArticleMolecular metabolism2019
Natural helix 9 mutants of PPARγ differently affect its transcriptional activity.
Article in Molecular metabolism, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 24 citations in OpenAlex.
- A simple and robust reporter-based framework for deep functional characterization of PPARγ mutants.Endocrinology · 2026Article
- Improved VPS4B O-GlcNAc modification triggers lipid droplets transferring from adipocytes to nasopharyngeal carcinoma cells.Cancer & metabolism · 2025Article
- Peroxisome proliferator-activated receptor gamma mutation in familial partial lipodystrophy type three: A case report and review of literature.World journal of diabetes · 2024Article
- Agonists of the Nuclear Receptor PPARγ Can Produce Biased Signaling.Molecular pharmacology · 2024Article
- Case report: two novel PPARG pathogenic variants associated with type 3 familial partial lipodystrophy in Brazil.Diabetology & metabolic syndrome · 2024Article
- Familial partial lipodystrophy resulting from loss-of-function PPARγ pathogenic variants: phenotypic, clinical, and genetic features.Frontiers in endocrinology · 2024Review
- Identification of an Evolutionarily Conserved Allosteric Network in Steroid Receptors.Journal of chemical information and modeling · 2023Article
- A structural mechanism of nuclear receptor biased agonism.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- PPARγ lipodystrophy mutants reveal intermolecular interactions required for enhancer activation.Nature communications · 2022Article
- Case Report: A New Peroxisome Proliferator-Activated Receptor Gamma Mutation Causes Familial Partial Lipodystrophy Type 3 in a Chinese Patient.Frontiers in endocrinology · 2022Article
- PPARgamma in Metabolism, Immunity, and Cancer: Unified and Diverse Mechanisms of Action.Frontiers in endocrinology · 2021Review
- Article
- Peroxisome proliferator-activated receptor gamma-ligand-binding domain mutations associated with familial partial lipodystrophy type 3 disrupt human trophoblast fusion and fibroblast migration.Journal of cellular and molecular medicine · 2020Article
- What lipodystrophies teach us about the metabolic syndrome.The Journal of clinical investigation · 2019Review
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Authors and funding
16 authors at 5 institutions in 2 countries.
Funding
Abstract
objectiveThe nuclear receptor PPARγ is the master regulator of adipocyte differentiation, distribution, and function. In addition, PPARγ induces terminal differentiation of several epithelial cell lineages, including colon epithelia. Loss-of-function mutations in PPARG result in familial partial lipodystrophy subtype 3 (FPDL3), a rare condition characterized by aberrant adipose tissue distribution and severe metabolic complications, including diabetes. Mutations in PPARG have also been reported in sporadic colorectal cancers, but the significance of these mutations is unclear. Studying these natural PPARG mutations provides valuable insights into structure-function relationships in the PPARγ protein. We functionally characterized a novel FPLD3-associated PPARγ L451P mutation in helix 9 of the ligand binding domain (LBD). Interestingly, substitution of the adjacent amino acid K450 was previously reported in a human colon carcinoma cell line.
methodsWe performed a detailed side-by-side functional comparison of these two PPARγ mutants.
resultsPPARγ L451P shows multiple intermolecular defects, including impaired cofactor binding and reduced RXRα heterodimerisation and subsequent DNA binding, but not in DBD-LBD interdomain communication. The K450Q mutant displays none of these functional defects. Other colon cancer-associated PPARγ mutants displayed diverse phenotypes, ranging from complete loss of activity to wildtype activity.
conclusionsAmino acid changes in helix 9 can differently affect LBD integrity and function. In addition, FPLD3-associated PPARγ mutations consistently cause intra- and/or intermolecular defects; colon cancer-associated PPARγ mutations on the other hand may play a role in colon cancer onset and progression, but this is not due to their effects on the most well-studied functional characteristics of PPARγ.
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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.