Abstract
Within the nuclear receptor family, Nur77 (also known as NGFI-B) distinguishes itself by its ability to bind a target sequence (the NBRE) as a monomer and by its role in T-cell receptor (TCR)-induced apoptosis in T cells. We now report on a novel mechanism of Nur77 action that is mediated by homodimers. These dimers bind a Nur77 response element (NurRE), which has been identified as a target of CRH-induced Nur77 in the pro-opiomelanocortin (POMC) gene promoter. Both halves of the palindromic NurRE are required for responsiveness to physiological signals, like CRH in pituitary-derived AtT-20 cells. Similarly, in T-cell hybridomas, TCR activation induced NurRE but not NBRE reporters. The in vivo signaling function of Nur77 thus appears to be mediated by dimers acting on a palindromic response element of unusual spacing between its half-sites. This mechanism may represent the biologically relevant paradigm of action for this subfamily of orphan nuclear receptors.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Colforsin / pharmacology
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Corticotropin-Releasing Hormone / pharmacology
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Cyclic AMP / physiology
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DNA / metabolism
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / metabolism*
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Dimerization
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Gene Expression Regulation / physiology
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Hybridomas
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Mice
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Mutation
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Nuclear Receptor Subfamily 4, Group A, Member 1
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Pituitary Gland, Anterior / cytology
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Pituitary Gland, Anterior / physiology*
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Pro-Opiomelanocortin / genetics*
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Promoter Regions, Genetic / genetics
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Receptors, Antigen, T-Cell / physiology
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Receptors, Cytoplasmic and Nuclear / genetics
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Receptors, Cytoplasmic and Nuclear / metabolism*
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Receptors, Steroid
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Signal Transduction / physiology*
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T-Lymphocytes / cytology
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T-Lymphocytes / physiology*
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Transcription Factors / genetics
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Transcription Factors / metabolism*
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Tumor Cells, Cultured
Substances
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DNA-Binding Proteins
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Nr4a1 protein, mouse
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Nuclear Receptor Subfamily 4, Group A, Member 1
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Receptors, Antigen, T-Cell
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Receptors, Cytoplasmic and Nuclear
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Receptors, Steroid
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Transcription Factors
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Colforsin
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Pro-Opiomelanocortin
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DNA
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Corticotropin-Releasing Hormone
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Cyclic AMP