Isolated nuclear receptor genes

The cDNAs for the glucocorticoid and the oestrogen receptors were isolated more than 15 years ago. They were among the first genes, coding for transcriptional gene activators, to be identified. The family of nuclear receptors is the largest family of transcription factors. Until now, more than 150 different members of the superfamily of nuclear receptors, from worms to insects to humans, have been described. The discovery of an insect receptor for a steroid hormone, ecdysone, indicated that this kind of receptor must have evolved prior to the separation of vertebrates and invertebrates. 

Recently, this system was used to identify several factors putatively involved in the mechanism of steroid hormone-mediated gene transcription. In a two-hybrid screen to identify factors that interact with the vitamin D receptor (VDR), we isolated transcription factor IIB (TFIIB) as a VDR-mteractive clone (2). The interaction of VDR, retinoic-acid receptors and other steroid-hormone receptors with TFIIB may represent a fundamental step in the mechanism of transcription mediated by the nuclear-receptor family (3-5) The two-hybrid system has also identified several putative coactivator and corepressor proteins that contact retinoid receptors, thyroid receptors, vitamin D receptors, and other members of the nuclear-receptor family (6-9) Thus, the two-hybrid system is playing an instrumental role in the identification of factors involved in nuclear receptor-mediated gene expression This chapter discusses several procedures and strategies used to establish a two-hybrid system to examine proteins that interact with retinoid receptors, with the VDR, or with nuclear receptors in general. 

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