Marcel

NRs in the absence of ligand binding are associated with other proteins either in the cytoplasm or in the nucleus. In the absence of ligand, steroid receptors form quaternary complexes with chaperones like heat shock proteins that prevent their interaction with DNA. RXR-heterodimeric receptors bind to their cognate DNA-response elements in the absence of ligand and cause transcrip-tional repression. In absence of ligand, NR is often associated with corepressor proteins inhibiting basal transcription of target genes. On ligand binding, steroid receptors dissociate from the chaperone proteins and associate with hormone response elements on the DNA and interact with coactivation proteins. Ligand binding changes the conformation of RXR-heterodimeric receptors and activates or

Figure 5 Schematic illustration of a nuclear hormone receptor. The highly conserved DBD (C) is flanked by less well conserved N-terminal and C-terminal regions. Ligand binds to the LBD (E), which is moderately conserved. Dimerization functions are located in the C and E regions. Ligand-dependent (AF2) and independent (AF1) transactivation functions are located in the receptor A/B and E domains, respectively. DNA binding is regulated by residues in the DBD (C) in cooperation with residues in the N-terminal (A/ B) region and hinge region (D).

Figure 5 Schematic illustration of a nuclear hormone receptor. The highly conserved DBD (C) is flanked by less well conserved N-terminal and C-terminal regions. Ligand binds to the LBD (E), which is moderately conserved. Dimerization functions are located in the C and E regions. Ligand-dependent (AF2) and independent (AF1) transactivation functions are located in the receptor A/B and E domains, respectively. DNA binding is regulated by residues in the DBD (C) in cooperation with residues in the N-terminal (A/ B) region and hinge region (D).

represses transcription of the genes by binding to various coactivators or corepres-sors.

Orphan Nuclear Receptors. Molecular cloning has identified several orphan receptors sharing similar structure to the nuclear receptors (Table 3). However, the ligands for these orphan receptors are not known at present. Some of these receptors have been recently matched with physiological ligands, e.g., 9-cis retinoic acid was found to bind and activate three of the nuclear receptors classified originally as orphan receptors and later named as RARs [2]. Similarly, though the physiological ligands of many orphan nuclear receptors have not been identified at present, they provided potentially important drug targets as in the case of orphan receptors like peroxisome proliferator activation receptor-y (PPARy), which plays a role in adipogenesis and the discovery of thiazolidienedi-ones in the treatment of noninsulin dependent diabetes and regulation of cholesterol metabolism by steroidogenic receptor (SF-1), liver L receptor a (LXRa), and farnesoid L receptor (FXR).

Was this article helpful?

0 0
Diabetes Sustenance

Diabetes Sustenance

Get All The Support And Guidance You Need To Be A Success At Dealing With Diabetes The Healthy Way. This Book Is One Of The Most Valuable Resources In The World When It Comes To Learning How Nutritional Supplements Can Control Sugar Levels.

Get My Free Ebook


Post a comment