| Steroid receptors possess many characteristics of transcription factors and provide a model for the role of zinc finger proteins in DNA binding
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| STEROID RECEPTOR GENE FAMILY |
| Gene superfamilies: steroid-thyroid-retinoic acid |
| The steroid receptor gene family, although large, is in fact only a subset of a much larger family of so-called nuclear hormone receptors. All members of this family have the same basic structure as the steroid hormone receptors: a hypervariable N-terminal region, a highly conserved DNA-binding region (49-85% homology), a variable hinge region, and a highly conserved ligand-binding domain (30-87% homology). They are separated into two groups. Type I receptors are a group of receptor proteins that form homodimers and bind specifically to steroid hormone response elements only in the presence of their ligand. Type II receptors form homodimers that can bind to response elements in the absence of their ligand, and may also form heterodimers with other type II receptor subunits, to form active units. The type II receptors include the thyroid hormone, vitamin D, and retinoic acid receptors. |
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| Steroid hormones have a broad range of functions in humans and are essential to normal life. They are derived from a common precursor, cholesterol, and thus share a similar structural backbone (Chapter 16). However, differences in hydroxylation of certain carbon atoms and aromatization of the steroid A-ring give rise to marked differences in biological effect. Steroids bring about their biological effects by binding to steroid-specific hormone receptors; these receptors are found in the cell cytoplasm and, on binding steroid molecules, undergo a series of changes that result in the steroid-receptor complex binding to DNA at a specific response element, a so-called steroid response element (SRE). SREs
may be found many kilobases upstream or downstream of the startpoint. The steroid-receptor complex functions as a sequence-specific transcription factor and binding of the complex to the SRE results in activation of the promoter and initiation of transcription (Fig. 33.4). As might be expected, because of the large number of steroids found in humans, there is a correspondingly large number of distinct steroid receptor proteins, and each of these recognizes a specific consensus sequence, the SRE, in the region of a promoter.
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