Overview of Nuclear Receptors

The adaptive response to xenobiotics is orchestrated in the cell by a subset of receptors that act primarily in the nucleus. For this chapter, we will employ a liberal definition of nuclear receptor (NR) that includes all signaling molecules that function as ligand-binding transcription factors that bind to specific DNA enhancer sequences and upregulate the transcription of CYP genes. Two classes of NRs will be discussed in this chapter. Members of the nuclear hormone receptor (NHR) superfamily to be reviewed include the constitutive androstane receptor (CAR), the pregnane X-receptor (PXR), and the peroxisome prolifera-tor activated receptors (PPARs). A single member of the PAS superfamily, the aryl hydrocarbon receptor (AHR), will also be discussed. 

Susanne N. Williams, Elizabeth Dunham, and Christopher A. Bradfield 

Cytochrome P450 Structure, Mechanism, and Biochemistry, 3e, edited by Paul R. Ortiz de Montellano Kluwer Academic / Plenum Publishers, New York, 2005. 

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Here we will focus on current progress in structural analyses of nuclear hormone receptors, and how these proteins interact with their ligands, both natural and pharmaceutical. We will provide first a general overview of nuclear receptors and then using several nuclear receptors as examples, we will discuss the receptor-ligand specificity throughout the nuclear receptor... 

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