TY - JOUR
AU - De Luca, Luigi M.
AB - <p>The divergent response and the molecular mechanisms underlying the anti-cancer effects of retinoid X receptor (RXR) ligand (rexinoid) therapy are poorly understood. This study demonstrates that ligand-activated RXR homodimer facilitated G<sub>1</sub> arrest by up-regulation of p21 <i>in vitro</i> and <i>in vivo</i> but failed to induce G<sub>1</sub> arrest when p21 expression was blocked by p21 small interfering RNA. RXR ligand-dependent p21 up-regulation was transcriptionally controlled through the direct binding of RXR homodimers to two consecutive retinoid X response elements in the p21 promoter. Structural overlap of a retinoic acid response element with these retinoid X response elements led to a high affinity binding of retinoic acid receptor/RXR heterodimer to the retinoic acid response element, resulting in the prevention of RXR ligand-mediated p21 transactivation. These data show that p21 is a potential and novel molecular target for RXR ligand-mediated anti-cancer therapy and that the expression level of retinoic acid receptor and RXR in tumors may be crucial to induce p21-mediated cell growth arrest in RXR ligand therapy.</p>
TI - p21WAF1/CIP1 Is a Common Transcriptional Target of Retinoid Receptors: PLEIOTROPIC REGULATORY MECHANISM THROUGH RETINOIC ACID RECEPTOR (RAR)/RETINOID X RECEPTOR (RXR) HETERODIMER AND RXR/RXR HOMODIMER * 
JO - Journal of Biological Chemistry
DO - 10.1074/jbc.m701700200
DA - 2007-10-12
UR - https://www.deepdyve.com/lp/american-society-for-biochemistry-and-molecular-biology/p21waf1-cip1-is-a-common-transcriptional-target-of-retinoid-receptors-VB8kfQ9AET
SP - 29987
EP - 29997
VL - 282
IS - 41
DP - DeepDyve
ER -