Identification of heme as the ligand for the orphan nuclear receptors REV-ERBalpha and REV-ERBbeta
| Autor: | Thomas P. Burris, Lorri L Burris, Keith R. Stayrook, Amanda K Nosie, Srilatha Raghuram, Fraydoon Rastinejad, Don B McClure, Sepideh Khorasanizadeh, Pengxiang Huang, Pamela M. Rogers |
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| Jazyk: | angličtina |
| Rok vydání: | 2007 |
| Předmět: |
Heme binding
Receptors Cytoplasmic and Nuclear Heme Biology Ligands DNA-binding protein Article Cell Line chemistry.chemical_compound Structural Biology Humans Receptor Molecular Biology Psychological repression Transcription factor Circular Dichroism Recombinant Proteins ARNTL DNA-Binding Proteins Repressor Proteins Nuclear receptor chemistry Biochemistry Gene Expression Regulation Spectrometry Mass Matrix-Assisted Laser Desorption-Ionization Nuclear Receptor Subfamily 1 Group D Member 1 Thermodynamics Spectrophotometry Ultraviolet Transcription Factors |
| Popis: | 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 1:1 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. ispartof: Nature Structural and Molecular Biology vol:14 issue:12 pages:1207-1213 ispartof: location:United States status: published |
| Databáze: | OpenAIRE |
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