Molecular determinants of the interactions between SRC-1 and LXR/RXR heterodimers

作者：Son You Lee; Lee Young Chul^*

来源：FEBS Letters, 2010, 584(18): 3862-3866.

DOI：10.1016/j.febslet.2010.07.056

• Liver X receptor
• Retinoid X receptor
• Heterodimer
• Steroid receptor coactivator-1
• NR box

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.
Structured summary: MINT-7986678, MINT-7986639, MINT-7986700, MINT-7986720, MINT-7986736, MINT-7986760, MINT-7986787:LXR (uniprotkb:Q13133) physically interacts (MI:0915) with SRC1 (uniprotkb:Q15788) and RXR (uniprotkb:P19793) by pull down (MI:0096)
MINT-7986596, MINT-7986621:SRC1 (uniprotkb:Q15788) physically interacts (MI:0915) with LXR (uniprotkb:Q13133) by pull down (MI:0096)
MINT-7986555, MINT-7986575:LXR (uniprotkb:Q13133) physically interacts (MI:0915) with SRC1 (uniprotkb:Q15788) by two hybrid (MI:0018)
MINT-7986808, MINT-7986907, MINT-7986890:SRC1 (uniprotkb:Q15788) binds (MI:0407) to LXR (uniprotkb:Q13133) by pull down (MI:0096)
MINT-7986822, MINT-7986848, MINT

• 出版日期2010-9-24