Thyroid hormone receptor homodimers can function as ligand-sensitive repressors.
Mol Endocrinol
; 9(5): 563-78, 1995 May.
Article
em En
| MEDLINE
| ID: mdl-7565804
ABSTRACT
Unlike the steroid hormone receptors that bind their response elements as homodimers, thyroid hormone receptor (TRs) as well as retinoic acid receptors and several other receptors have been shown to require heterodimerization with retinoid X receptors (RXR) for efficient binding to most response elements. In this article we have compared in detail TR DNA binding and its gene-regulatory characteristics in the presence and absence of RXR. We observe that in the absence of RXR, TRs are able to bind with high affinity as homodimers to a subset of thyroid hormone response elements consisting of two AGGTCA motifs arranged as inverted palindromes. This binding is inhibited by T3, which prevents TR homodimers from functioning as ligand-dependent transcriptional activators. We demonstrate that TR homodimers can act as potent ligand-responsive repressors, in particular when binding to sites 3' of the TATA box. Thus, TRs appear to have important regulatory functions in the absence of RXRs. This is strongly supported by our observations that some naturally occurring TR beta mutants that have been associated with generalized thyroid hormone resistance as well as the v-erbA oncogene are defective in this activity. Thus ligand-sensitive repression by TRs is an important regulatory mechanism.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Receptores dos Hormônios Tireóideos
/
Receptores do Ácido Retinoico
Tipo de estudo:
Diagnostic_studies
Limite:
Animals
Idioma:
En
Revista:
Mol Endocrinol
Assunto da revista:
BIOLOGIA MOLECULAR
/
ENDOCRINOLOGIA
Ano de publicação:
1995
Tipo de documento:
Article
País de afiliação:
Estados Unidos