Identification of heme as the ligand for the orphan nuclear receptors REV-ERBalpha and REV-ERBbeta.
Nat Struct Mol Biol
; 14(12): 1207-13, 2007 Dec.
Article
em En
| MEDLINE
| ID: mdl-18037887
ABSTRACT
The nuclear receptors REV-ERBalpha (encoded by NR1D1) and REV-ERBbeta (NR1D2) have remained orphans owing to the lack of identified physiological ligands. Here we show that heme is a physiological ligand of both receptors. Heme associates with the ligand-binding domains of the REV-ERB receptors with a 11 stoichiometry and enhances the thermal stability of the proteins. Results from experiments of heme depletion in mammalian cells indicate that heme binding to REV-ERB causes the recruitment of the co-repressor NCoR, leading to repression of target genes including BMAL1 (official symbol ARNTL), an essential component of the circadian oscillator. Heme extends the known types of ligands used by the human nuclear receptor family beyond the endocrine hormones and dietary lipids described so far. Our results further indicate that heme regulation of REV-ERBs may link the control of metabolism and the mammalian clock.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Proteínas Repressoras
/
Fatores de Transcrição
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Receptores Citoplasmáticos e Nucleares
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Proteínas de Ligação a DNA
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Heme
Idioma:
En
Ano de publicação:
2007
Tipo de documento:
Article