Sensors for Metabolic Control

A Regulatory Network of Nuclear Receptors
  • Béatrice Desvergne
  • Liliane Michalik
  • Walter Wahli
Part of the Endocrine Updates book series (ENDO, volume 17)


Nuclear receptors are transcription factors characterized by two important properties: first, they are activated upon the binding of specific ligands for which they have high affinity and low capacity; second, they bind to specific response elements located in the vicinity of the promoter of their target genes (see Chapter 12). Thus, in a simplified view, the effector function of the nuclear receptors in a cell is to adapt the gene expression program according to the signals that they receive in form of specific ligands. Nuclear receptors share a common modular organization. A poorly structured N-terminal domain that may encompass a ligand-independent transactivation domain is followed by the DNA binding domain (DBD) comprised of two zinc fingers which is the hallmark of the nuclear receptor family. A hinge region then links the DNA binding domain to the ligand binding domain (LBD) that has a general fold structured by 12 α helices and 3 β sheets. Nuclear receptors bind to DNA in form of dimers, either homodimers or more often heterodimers with the receptor for 9-cis retinoic acid known as RXR. The DNA response element of nuclear receptors is formed of two sequences corresponding to or closely related to the hexamer AGGTCA. Their organisation in direct repeats or palindromic arrays and the length of the spacing between the two hexamers determine the specificity of these response elements towards each dimer of family members. The general scheme for transactivation via nuclear receptors is believed to occur in at least two steps. In the absence of ligand, the nuclear receptor dimer binds to a co-repressor protein that inhibits its transactivation properties. In the presence of ligand, or due to an alternative pathway of activation such as phosphorylation, the co-repressor is released and a coactivator is recruited, allowing further contacts to be made with the transcription machinery, eventually resulting in transcription enhancement (also see Chapters 12 and 13).


Bile Acid Nuclear Receptor Bile Acid Synthesis Orphan Nuclear Receptor Orphan Nuclear Hormone Receptor 
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Copyright information

© Springer Science+Business Media New York 2002

Authors and Affiliations

  • Béatrice Desvergne
    • 1
  • Liliane Michalik
    • 1
  • Walter Wahli
    • 1
  1. 1.Institute of Animal Biology, Faculty of SciencesUniversity of Lausanne, Bâtiment BiologieLausanneSwitzerland

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