FORMATION OF RETINOID-X RECEPTOR HOMODIMERS LEADS TO REPRESSION OF T(3) RESPONSE - HORMONAL CROSS-TALK BY LIGAND-INDUCED SQUELCHING

被引:102
作者
LEHMANN, JM [1 ]
ZHANG, XK [1 ]
GRAUPNER, G [1 ]
LEE, MO [1 ]
HERMANN, T [1 ]
HOFFMANN, B [1 ]
PFAHL, M [1 ]
机构
[1] LA JOLLA CANC RES FDN, CTR CANC, LA JOLLA, CA 92037 USA
关键词
D O I
10.1128/MCB.13.12.7698
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Thyroid hormone receptors (TRs) form heterodimers with retinoid X receptors (RXRs). Heterodimerization is required for efficient TR DNA binding to most response elements and transcriptional activation by thyroid hormone. RXRs also function as auxiliary proteins for several other receptors. In addition, RXRalpha can be induced by specific ligands to form homodimers. Here we report that RXR-specific retinoids that induce RXR homodimers are effective repressors of the T3 response. We provide evidence that this repression by RXR-specific ligands occurs by sequestering of RXR from TR-RXR heterodimers into RXR homodimers. This ligand-induced squelching may represent an important mechanism by which RXR-specific retinoids and 9-cis retinoic acid mediate hormonal cross talk among a subfamily of nuclear receptors activated by structurally unrelated ligands.
引用
收藏
页码:7698 / 7707
页数:10
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