IDEAS home Printed from https://ideas.repec.org/a/nat/nature/v396y1998i6709d10.1038_24634.html
   My bibliography  Save this article

Interdomain communication regulating ligand binding by PPAR-γ

Author

Listed:
  • Dalei Shao

    (Diabetes, and Metabolism)

  • Shamina M. Rangwala

    (Diabetes, and Metabolism)

  • Shannon T. Bailey

    (Diabetes, and Metabolism)

  • Samuel L. Krakow

    (Diabetes, and Metabolism)

  • Mauricio J. Reginato

    (Departments of Pharmacology)

  • Mitchell A. Lazar

    (Diabetes, and Metabolism
    Genetics, University of Pennsylvania School of Medicine)

Abstract

Binding to receptors in the cell nucleus is crucial for the action of lipophilic hormones and ligands. PPAR-γ (for peroxisome proliferator-activated receptor) is a nuclear hormone receptor that mediates adipocyte differentiation1,2 and modulates insulin sensitivity3, cell proliferation4 and inflammatory processes5,6. PPAR-γ ligands have been implicated in the development of atherogenic foam cells7 and as potential cancer treatments8. Transcriptional activity of PPAR-γ is induced by binding diverse ligands, including natural fatty acid derivatives9,10,11, antidiabetic thiazolidinediones12, and non-steroidal anti-inflammatory drugs13. Ligand binding by PPAR-γ, as well as by the entire nuclear-receptor superfamily, is an independent property of the carboxy-terminal ligand-binding domain (LBD) of the receptor14,15. Here we show that ligand binding by PPAR-γ is regulated by intramolecular communication between its amino-terminal A/B domain and its carboxy-terminal LBD. Modification of the A/B domain, for example by physiological phosphorylation by MAP kinase, reduces ligand-binding affinity, thus negatively regulating the transcriptional and biological functions of PPAR-γ. The ability of the A/B domain to regulate ligand binding has important implications for the evaluation and mechanism of action of potentially therapeutic ligands that bind PPAR-γ and that are likely to extend to other members of the nuclear-receptor superfamily.

Suggested Citation

  • Dalei Shao & Shamina M. Rangwala & Shannon T. Bailey & Samuel L. Krakow & Mauricio J. Reginato & Mitchell A. Lazar, 1998. "Interdomain communication regulating ligand binding by PPAR-γ," Nature, Nature, vol. 396(6709), pages 377-380, November.
  • Handle: RePEc:nat:nature:v:396:y:1998:i:6709:d:10.1038_24634
    DOI: 10.1038/24634
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/24634
    File Function: Abstract
    Download Restriction: Access to the full text of the articles in this series is restricted.

    File URL: https://libkey.io/10.1038/24634?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    As the access to this document is restricted, you may want to search for a different version of it.

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. Justin A Lemkul & Stephanie N Lewis & Josep Bassaganya-Riera & David R Bevan, 2015. "Phosphorylation of PPARγ Affects the Collective Motions of the PPARγ-RXRα-DNA Complex," PLOS ONE, Public Library of Science, vol. 10(5), pages 1-21, May.
    2. Maria Stahl Madsen & Marjoleine F. Broekema & Martin Rønn Madsen & Arjen Koppen & Anouska Borgman & Cathrin Gräwe & Elisabeth G. K. Thomsen & Denise Westland & Mariette E. G. Kranendonk & Marian Groot, 2022. "PPARγ lipodystrophy mutants reveal intermolecular interactions required for enhancer activation," Nature Communications, Nature, vol. 13(1), pages 1-19, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:nature:v:396:y:1998:i:6709:d:10.1038_24634. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    We have no bibliographic references for this item. You can help adding them by using this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.