Nuclear receptor-regulated gene transcription

Small molecules constitute the ultimate goal in the search for compounds that can directly block the nuclear receptor-cofactor interaction. Such compounds would not only constitute a new pharmacological and cell biological tool to modulate nuclear receptor-regulated gene transcription, but are also envisaged to provide a new entry in nuclear receptor antagonism. 

Another example is a recently discovered second mode of action by which nuclear receptors modulate transcription. In contrast to DNA-binding-dependent mechanisms, cross talk refers here to gene regulation by protein-protein-interaction of nuclear receptors with other transcription factors, such as AP-1 or NF-kB. Consequently, the nuclear receptor acts as a corepressor or coactivator of transcription. 

Nuclear Receptor Regulation of Hepatic Cytochrome P450 Enzymes. Figure 1 General mechanism for transcriptional activation of CYP genes by xenochemicals that activate their cognate xeno-receptor proteins. In the case of Ah receptor, the receptor s heterodimerization partner is Arnt, whereas in the case of the nuclear receptors CAR, PXR, and PPARa, the heterodimerization partner is RXR. The coactivator and basal transcription factor complexes shown are each comprised of a large number of protein components. 

Boonyaratanakomkit V, Bi Y, Rudd M, Edwards DP (2008) The role and mechanism of progesterone receptor activation of extra-nuclear signaling pathways in regulating gene transcription and ceU cycle progression. Steroids 73 922-928... 

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