+ Resolve Article
+ Follow Us
Follow on FacebookFollow on Facebook
Follow on TwitterFollow on Twitter

+ Translate
+ Subscribe to Site Feed
GeoScience Most Shared ContentMost Shared Content

Selective ligand activity at Nur/retinoid X receptor complexes revealed by dimer-specific bioluminescence resonance energy transfer-based sensors

, : Selective ligand activity at Nur/retinoid X receptor complexes revealed by dimer-specific bioluminescence resonance energy transfer-based sensors. Faseb Journal 29(10): 4256-4267

Retinoid X receptors (RXRs) play a role as master regulators because of their capacity to form heterodimers with other nuclear receptors (NRs). Accordingly, retinoid signaling is involved in multiple biologic processes, including development, cell differentiation, metabolism, and cell death. However, the role and function of RXRs in different heterodimer complexes remain unidentified, mainly because most RXR drugs (called rexinoids) are not selective of specific heterodimer complexes. The lack of selectivity strongly limits the use of rexinoids for specific therapeutic approaches. To better characterize rexinoids at specific NR complexes, we have developed and optimized luciferase (Luc) protein complementation(PCA)-based bioluminescence resonance energy transfer (BRET) assays that can directly measure recruitment of a coactivator (CoA) motif fused to yellow fluorescent protein (YFP) by specific NR dimers. To validate the assays, we compared rexinoid modulation of CoA recruitment by the RXR homodimer and by the heterodimers Nur77/RXR and Nurr1/RXR. Results revealed that some rexinoids display selective CoA recruitment activities with homo- or heterodimer complexes. In particular, SR11237 (BMS649) has stronger potency for recruitment of CoA motif and transcriptional activity with the heterodimer Nur77/RXR than other complexes. This technology should be useful in identifying new compounds with specificity for individual dimeric species formed by NRs.


PMID: 26148973

DOI: 10.1096/fj.14-259804

Other references

Sblattero, D.; Florian, F.; Azzoni, E.; Not, T.; Ventura, A.; Bradbury, A.; Marzari, R., 2000: Site of synthesis of antibodies to a-gliadin and tissue-transglutaminase in celiac disease patients. JPGN 31(Supplement 2): S214

Anonymous, 2004: Patient card. Tips on taking an oral anticoagulant (antivitamin K). La Revue du Praticien 54(3): 310-310

Abdel Malak, K.K.I.; Makram, E.A., 1996: The proper dose of potassium fertilizer and its application timing for Giza 83 cotton cultivar grown in upper Egypt. In field trials in 1994-95 at Mallawi Agricultural Research Station, Menia governorate, cotton cv. Giza 83 was given 24 or 48 kg K2O/feddan after thinning, at the beginning of flowering or 50% after thinning + 50% at flowering. Seed cotton yield w...

Caputto, R.; Maccioni, A.H.R.; Caputto, B.L., 1977: Activation of deoxy cholate solubilized atpase by ganglioside and asialo ganglioside preparations. ATPase was prepared from [rat] brain microsomes by solubilization with sodium deoxycholate and fractionated at different concentrations of (NH4)2SO4. The Mg2+-ATPase was activated by total brain gangliosides, disialoganglioside, monosialogangliosi...

Cha-Cha, R.; Fernandes, F.; Romano, A., 2003: Conservacao de polystichum drepanum(Sw.) C. presl, pterifofito endemico da ilha da Madeira. Polystichum drepanum (Sw) C. Presl is a threatened fern endemic to Madeira Island, very rare and confined to a few forest areas in the northwest of this island. Due to this situation it is urgent the development of studies to propagate this specie...

Sie, H.G.; Valkema, A.J.; Loomeijer, F.J., 1967: Re-evaluation of radio-iodinated triolein as a test fat in fat absorption studies. The absorption of radio-iodinated triolein was compared to that of glyceryl-trioleate-14C in rats. The results obtained showed that there was no difference in the absorption of these two radioactive fats as determined by the radioactivity in the s...

Brener, S.J.; Oldroyd, K.G.; Maehara, A.; El-Omar, M.; Witzenbichler, B.; Xu, K.; Mehran, R.; Gibson, C.Michael.; Stone, G.W., 2014: Outcomes in patients with ST-segment elevation acute myocardial infarction treated with clopidogrel versus prasugrel (from the INFUSE-AMI trial). Prasugrel is more potent than clopidogrel, but it is not known whether this translates into clinical benefit in patients undergoing primary percutaneous coronary intervention (PCI) with bivalirudin for ST elevation myocardial infarction. In the In...

Bentov, Y.; Sheiner, E.; Kenigsberg, S.; Mazor, M., 2003: Mediterranean spotted fever during pregnancy: case presentation and literature review. Mediterranean spotted fever (MSF) is caused by Rickettsia conorii, an obligate intracellular parasite of eukaryotic cells. Although, usually this disease has a benign course, a rapidly fatal outcome can occur even in young healthy adults. We descr...

Euzenat, O.; Guibert, A.; Combes, D., 1997: Production of fructo-oligosaccharides by levansucrase from Bacillus subtilis C4. The production of levans from sucrose by levansucrase (EC from Bacillus subtilis C4 was studied in relation to temperature (37, 50 or 60 degrees C) and sucrose concentration (1.0-2.6 M). These experiments demonstrated the ability of leva...

Meyer, C.M., 1989: Pretreatment arbitration agreement: if you haven't done it right, you haven't done it at all!. Colorado Medicine 86(4): 68-69