HX531, a retinoid X receptor antagonist, inhibited the 9-cis retinoic acid-induced binding with steroid receptor coactivator-1 as detected by surface plasmon resonance. Export

@article{citeulike:2352923, abstract = {HX531 is a retinoid X receptor (RXR) antagonist that inhibits 9-cis retinoic acid-induced neutrophilic differentiation of HL-60 cells. In order to elucidate the inhibitory mechanism of HX531, we have developed a novel ligand sensor assay for RXR in which the receptor-coactivator interaction is directly monitored using surface plasmon resonance (SPR) biosensor technology. A 20-mer peptide from steroid receptor coactivator-1 (SRC-1), containing nuclear receptor interaction motif LXXLL was immobilized on the surface of a BIAcore sensor chip. Injection of human recombinant RXR with or without 9-cis retinoic acid resulted in ligand-dependent interaction with the SRC-1 peptide. Kinetic analysis revealed dissociation constants (KD) of 9-cis RA-preincubated RXR to SRC-1 was 5.92 x 10(-8)M. Using this technique, we found that 1 microM HX531 reduced the ka value of liganded-RXR with SRC-1, suggesting that HX531 reduced the affinity of RXR to SRC-1. This SPR assay system was applied to obtain quantitative kinetic data of RXR ligand binding to the SRC-1 peptide and the alteration of these data by antagonists.}, address = {National Institute of Health Sciences, 1-18-1, Kamiyoga, Setagaya-ku, 158-8501 Tokyo, Japan.}, author = {Kanayasu-Toyoda, T. and Fujino, T. and Oshizawa, T. and Suzuki, T. and Nishimaki-Mogami, T. and Sato, Y. and Sawada, J. and Inoue, K. and Shudo, K. and Ohno, Y. and Yamaguchi, T.}, citeulike-article-id = {2352923}, citeulike-linkout-0 = {http://dx.doi.org/10.1016/j.jsbmb.2004.11.007}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/15857749}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=15857749}, doi = {10.1016/j.jsbmb.2004.11.007}, issn = {0960-0760}, journal = {J Steroid Biochem Mol Biol}, keywords = {9-cisra, hl-60, rxr}, month = {March}, number = {4}, pages = {303--309}, posted-at = {2008-02-08 10:33:07}, priority = {4}, title = {HX531, a retinoid X receptor antagonist, inhibited the 9-cis retinoic acid-induced binding with steroid receptor coactivator-1 as detected by surface plasmon resonance.}, url = {http://dx.doi.org/10.1016/j.jsbmb.2004.11.007}, volume = {94}, year = {2005} }

TY - JOUR ID - citeulike:2352923 L3 - citeulike-article-id:2352923 N2 - HX531 is a retinoid X receptor (RXR) antagonist that inhibits 9-cis retinoic acid-induced neutrophilic differentiation of HL-60 cells. In order to elucidate the inhibitory mechanism of HX531, we have developed a novel ligand sensor assay for RXR in which the receptor-coactivator interaction is directly monitored using surface plasmon resonance (SPR) biosensor technology. A 20-mer peptide from steroid receptor coactivator-1 (SRC-1), containing nuclear receptor interaction motif LXXLL was immobilized on the surface of a BIAcore sensor chip. Injection of human recombinant RXR with or without 9-cis retinoic acid resulted in ligand-dependent interaction with the SRC-1 peptide. Kinetic analysis revealed dissociation constants (KD) of 9-cis RA-preincubated RXR to SRC-1 was 5.92 x 10(-8)M. Using this technique, we found that 1 microM HX531 reduced the ka value of liganded-RXR with SRC-1, suggesting that HX531 reduced the affinity of RXR to SRC-1. This SPR assay system was applied to obtain quantitative kinetic data of RXR ligand binding to the SRC-1 peptide and the alteration of these data by antagonists. IS - 4 JF - J Steroid Biochem Mol Biol SN - 0960-0760 AD - National Institute of Health Sciences, 1-18-1, Kamiyoga, Setagaya-ku, 158-8501 Tokyo, Japan. EP - 309 TI - HX531, a retinoid X receptor antagonist, inhibited the 9-cis retinoic acid-induced binding with steroid receptor coactivator-1 as detected by surface plasmon resonance. VL - 94 SP - 303 KW - 9-cisra KW - hl-60 KW - rxr AU - Kanayasu-Toyoda, T AU - Fujino, T AU - Oshizawa, T AU - Suzuki, T AU - Nishimaki-Mogami, T AU - Sato, Y AU - Sawada, J AU - Inoue, K AU - Shudo, K AU - Ohno, Y AU - Yamaguchi, T PY - 2005/03// UR - http://dx.doi.org/10.1016/j.jsbmb.2004.11.007 ER -