COUP receptor

RXR can form heterodimers with a wide variety of other nuclear-acting receptors, including those for vitamin D (section 11.3.3), thyroid hormone (section 11.15.3-3), long-chain polyunsaturated fatty acids derivatives (the so-called PPAR receptor) and one for which the physiological ligand has not yet been identified (the COUP receptor). 

Figure 2.6. Interactions of all-trans- and 9-cis-retinoic acids (and other active retinoids) with retinoid receptors. COUP, chicken ovaibumin upstream promoter.

Nuclear receptors for the steroid hormone ecdysone in Drosophila deserve special consideration, for several reasons. First, the insect hormone ecdysone (Fig. 11.2) was the first steroid hormone shown to act at the level of the gene, because it induced puffs in the giant chromosomes of the fruitfly. Secondly, ecdysone activates the developmental programme of Drosophila, and, finally, the sequences of the DNA-binding domain (DBD) of the Drosophila nuclear ecdysone receptor and of receptor homologues (for example, the COUP-TFs chicken ovalbumin upstream promoter transcription factors) are highly conserved and nearly identical in vertebrates and humans. 

McCormack, D. G., Mak, J. C. W., Coupe, M. O., and Barnes, P. J. (1989). Calcitonin gene-related peptide vasodilation of human pulmonary vessels receptor mapping and functional studies. J. Appl. Physiol. 67, 1265-1270. 

Abbreviations IR inverted repeat DR direct repeat ER everted repeat NR no repeat . Numbers of HREs give the number of pairs separating the half-sites. R purine. Y pyrimidine. NGFI Nerve growth factor induced receptor COUP-TF CHicken ovalbumin upstream promoter transcription factor ROR Retinoic acid related orphan receptor, a, p und y are receptor subtypes coded by distinct genes. After Mangelsdorf et al, 1995. 

Wu, Q., Li, Y., Liu, R., Agadir, A., Lee, M.O., Liu, Y. and Zhang, X. (1997) Modulation of retinoic acid sensitivity in lung cancer cells through dynamic balance of orphan receptors nur77 and COUP-TF and their heterodimerization. The EMBO Journal, 16, 1656-1669. 

Schrader, M., Danielsson, C., Wiesenberg, I., and Carlberg, C. (1996) Identification of natural monomeric response elements of the nuclear receptor RZR/ROR. They also bind COUP-TF homodimers. J. Biol. Chem. 271, 19732-19736. 

These are DNA-binding proteins that show homologies with steroid hormone receptors and possess the double zinc finger motif, but for whom the true physiological ligands are unknown. One of these, COUP-TF, and a structurally very similar COUP-TF... 

Tsai, Tsai O Malley, 1991). These elements have a core sequence of an imperfect repeat A/GGGTCA, separated by a single nucleotide (GTGTCAAAG-GTCAAA). COUP-TF is a 45 kDa protein able to bind to many different A/GGGTCA repeats, which are also bound by dihydroxycalciferol, thyroid and retinoic acid receptors (Cooney et al, 1993) and can activate or repress transcription depending on the promoter context. It has been found in a number of different tissues in different species. Hepatic nuclear factor (HNF-4) is another orphan member of this superfamily. 

COUP-TFI and HNF-4 Binds to a Nnclear Receptor-Responsive Elemoit (NRRE) in the Mitochondrial HMG-CoA Synthase Gene... 

The abbreviations used are HMG-CoA, 3-hydroxy-3-melhylglutaryl-CoA CAT, chloramphenicol acetyltransferase PPAR, peroxisome proliferator-activated receptor PPRE, peroxisome proliferator-responsive element NRRE, nuclear receptor responsive element RXR, retinoid X receptor hRXRa, human 9-cis-retinoic acid receptor a mPPARa, mouse peroxisome proliferator-activated receptor a COUP-TP, chicken ovalbumin upstream-promoter transcription factor, HNF-4, hepatocyte nuclear factor 4 EMSA, electrophoretic mobility shift analysis tk, thymidine kinase NEFA, nonesterified fatty acids... 

Kruse, S. W., K. Suino-Powell, X. E. Zhou, et al. 2008. Identification of Coup-Tfii Orphan Nuclear Receptor as a Retinoic Acid-Activated Receptor. Plos Biol 6, no 9 2002-15. Lampert, J. M., J. Holzschuh, S. Hessel, et al. 2003. Provitamin A Conversion to Retinal Via the P,P-Carotene-15,15 -Oxygenase (Bcox) Is Essential for Pattern Formation and Differentiation During Zehrafish Emhryogenesis. Development 130, no 10 2173-86. 

Khewer, S. A., Umesono, K., Heyman, R A., Mangelsdorf, D J., Dyck, J. A, and Evans, R M (1992a) Retinoid X receptor-COUP-TF interactions modulate retinoic acid signaling. PNAS, 89, 1448-1452. 

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