Ligand-activated transcription

The mechanisms of corticosteroid receptor regulation of transcription have been elucidated. Both type I and type II corticosteroid receptors are members of a superfamily of ligand-activated transcription factors defined by protein sequence similarity. Included in this superfamily are various other steroid receptors, such as the estrogen receptor, as well as members of the retinoic acid receptor... 

The physiological effects of progesterone are mediated by two progesterone receptor isoforms termed PR-A and PR-E. These arise from a single gene and act as ligand-activated transcription factors to regulate the expression of... 

Ligand-activated transcription factors are also important in embryo genesis. TCDD also causes malformations via this mechanism, as do retinoids and glucocorticoids. The importance... 

Proteins in a family of ligand-activated transcription factors, the peroxisome proliferator-activated receptors (PPARs), respond to changes in dietary lipid by... 

Burbach KM, Poland A, Bradfield CA. 1992. Cloning of the Ah-receptor cDNA reveals a novel ligand-activated transcription factor. Proc Natl Acad Sci USA 89 8185-8189. 

Like other nuclear receptors (e.g., steroid hormone receptors, thyroid hormone receptors) the PPARs function as ligand-activated transcription factors. As illustrated in Fig. 1 (see color insert) individual PPARs function as dimers with members of the retinoid X receptor (RXR) family (23). Evidence for an interaction of PPARs with RXRs includes co-expression studies that were performed with yeast lacking endogenous nuclear receptors (24). 

Interaction with intracellular receptor which acts as a ligand-activated transcription factor the product of which affect immune response by unknown mechanisms... 

Fig. 8.2 The ligand-binding domain of the nuclear receptor RXR binds the small molecule 9-cis retinoic acid 9-cis RA). In the apo-structure on the left, helix 12 (H12) extends out into the solution. Upon binding 9-cis RA, HI2 folds back on top of the ligand and LBD creating a binding site for the transcription machinery. The transcription machinery is thereby recruited to the transcription start site, resulting in activation of transcription. Nuclear receptors generally follo A/ this mechanism of ligand-activated transcription. Coordinates from ILBD [9] and 1 FBY [10].

Nuclear receptors (NR) function as ligand-activated transcription factors that regulate expression of a host of genes, including those coding for key drug-metabolizing enzymes and transporters. It is now known that the induction... 

The mechanisms of induction or inhibition of the induction of these CYPs are primarily due to activation or inhibition of ligand-activated transcription... 

Nuclear hormone receptors (NRs) are ligand-activated transcription factors that regulate gene expression by interacting with hormone response elements on target genes (see also Chapter 12). This occurs via the formation of monomers, homodimers, or heterodimers generally with the retinoid X receptor (RXR) and interaction with the hormone response element [83,84],... 

Peroxisome proliferator activated receptors (PPARs) are members of the nuclear hormone receptors superfamily of ligand-activated transcription factors that are related to retinoid, steroid and thyroid receptors. All members of this superfamily have a similar structure the amino-terminal region allows ligand-independent activation, confers con-... 

Ligand-Activated Transcription Factors Xenobiotic Detection... 

Dioxin-like compounds are those chemicals that act as ligands for the aryl hydrocarbon receptor (AhR), which appears to be present in most vertebrate classes92. The AhR functions as a ligand-activated transcription factor and is responsible for most of the toxic consequences of dioxin-like compounds150, which can be diverse and include cardiovascular dysfunctions, immunosuppression and embryotoxicity24. Usually, the most potent ligand for the AhR and the most toxic compound is TCDD. Some important classes of ecotoxicants contain members that are AhR active (Table 4). 

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