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Mol. Cell. Biol., Dec 1997, 6887-6897, Vol 17, No. 12
Copyright © 1997, American Society for Microbiology

Differential recognition of liganded and unliganded thyroid hormone receptor by retinoid X receptor regulates transcriptional repression

J Zhang, I Zamir and MA Lazar
Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia 19104, USA.

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.

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