Abstract
Estrogen-related receptor gamma (ERRgamma) is an orphan nuclear receptor highly expressed in heart, skeletal muscle, kidney, and brain. To identify activation function-1 (AF-1)-dependent cofactors involved in the transcriptional function of ERRgamma, we screened for human cDNAs coding for proteins that bind to the bacterial expressed AF-1 by biopanning of a phage display library. Phages displaying fusion proteins with full-length PNRC2 (proline-rich nuclear receptor co-regulatory protein 2), already shown to be a cofactor for other nuclear receptors, and with a polypeptide of the bHLH corepressor TLE1 bound to the AF-1 containing bait. Pull-down analyses demonstrated a direct interaction of the receptor with the newly identified full-length proteins. Surprisingly, not only PNRC2 but also the corepressor TLE1 functioned as ERRgamma coactivator in a reporter gene analysis.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Binding Sites
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Brain / metabolism*
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Brain Chemistry
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Cells, Cultured
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Chlorocebus aethiops
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Co-Repressor Proteins
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Humans
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Nuclear Proteins / chemistry
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Nuclear Proteins / genetics
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Nuclear Proteins / metabolism*
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Protein Binding
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Protein Structure, Tertiary
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Receptors, Cytoplasmic and Nuclear / chemistry
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Receptors, Cytoplasmic and Nuclear / genetics
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Receptors, Cytoplasmic and Nuclear / metabolism*
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Receptors, Estrogen / chemistry
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Receptors, Estrogen / genetics
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Receptors, Estrogen / metabolism*
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Receptors, Interferon / chemistry
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Receptors, Interferon / genetics
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Receptors, Interferon / metabolism*
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Recombinant Fusion Proteins / chemistry
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Recombinant Fusion Proteins / genetics
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Recombinant Fusion Proteins / metabolism
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Repressor Proteins*
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Trans-Activators / chemistry
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Trans-Activators / genetics
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Trans-Activators / metabolism*
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Transcription Factors / physiology*
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Transcriptional Activation
Substances
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Co-Repressor Proteins
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ESRRG protein, human
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IFNGR2 protein, human
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Ifngr2 protein, mouse
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Nuclear Proteins
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PNRC2 protein, human
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Receptors, Cytoplasmic and Nuclear
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Receptors, Estrogen
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Receptors, Interferon
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Recombinant Fusion Proteins
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Repressor Proteins
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TLE1 protein, human
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Trans-Activators
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Transcription Factors