Open AccessDifferential Recognition of Liganded and Unliganded Thyroid Hormone Receptor by Retinoid X Receptor Regulates Transcriptional Repression
Author(s) -
J Zhang,
Iris Zamir,
Mitchell A. Lazar
Publication year - 1997
Publication title -
molecular and cellular biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.14
H-Index - 327
eISSN - 1067-8824
pISSN - 0270-7306
DOI - 10.1128/mcb.17.12.6887
Subject(s) - corepressor , thyroid hormone receptor , retinoid x receptor , biology , psychological repression , nuclear receptor , receptor , microbiology and biotechnology , thyroid hormone receptor beta , heptad repeat , transcription factor , hormone receptor , genetics , gene , peptide sequence , gene expression , cancer , breast cancer
Thyroid hormone receptor (TR) functions as part of multiprotein complexes that also include retinoid X receptor (RXR) and transcriptional coregulators. We have found that both the TR CoR box and ninth heptad are required for RXR interaction and in turn for interaction with corepressor proteins N-CoR and SMRT. Remarkably, the recruitment of RXR to repression-defective CoR box and ninth-heptad mutants via a heterologous dimerization interface restores both corepressor interaction and repression. The addition of thyroid hormone obviates the CoR box requirement for RXR interaction, provided that the AF2 activation helix at the C terminus of TR is intact. These results indicate that RXR differentially recognizes the unliganded and liganded conformations of TR and that these differences appear to play a major role in the recruitment of corepressors to TR-RXR heterodimers.