Molecular determinants of the interactions between SRC-1 and LXR/RXR heterodimers.
Liver X receptor (LXR)/retinoid X receptor (RXR) heterodimers have been shown to perform critical functions in cholesterol and lipid metabolism. Here, we have conducted a comparative analysis of the contributions of LXR and RXR binding to steroid receptor coactivator-1 (SRC-1), which contains three copies of the NR box. We demonstrated that the coactivator-binding surface of LXR, but not that of RXR, is critically important for physical and functional interactions with SRC-1, thereby confirming that RXR functions as an allosteric activator of SRC-1-LXR interaction. Notably, we identified NR box-2 and -3 as the essential binding targets for the SRC-1-induced stimulation of LXR transactivity, and observed the competitive in vitro binding of NR box-2 and -3 to LXR.
Son
You Lee
YL
Hormone Research Center, School of Biological Sciences and Technology, Chonnam National University, Gwangju, South Korea.
Lee
Young Chul
YC
D001667:Binding, Competitive; D002460:Cell Line; D006801:Humans; D000071518:Liver X Receptors; D056920:Nuclear Receptor Coactivator 1 / Q000235:genetics / Q000378:metabolism*; D057093:Orphan Nuclear Receptors / Q000235:genetics / Q000378:metabolism*; D055503:Protein Multimerization; D047488:Retinoid X Receptors / Q000235:genetics / Q000378:metabolism*; D020798:Two-Hybrid System Techniques
D000071518:Liver X Receptors; D057093:Orphan Nuclear Receptors; D047488:Retinoid X Receptors; D056920:Nuclear Receptor Coactivator 1