Abstract
In the absence of specific high-affinity agonists and antagonists, it has been difficult to define the target genes and biological responses attributable to many of the orphan nuclear receptors (ONRs). Indeed, it appears that many members of this receptor superfamily are not regulated by classical small molecules but rather their activity is controlled by interacting cofactors. Motivated by this finding, we have developed an approach to genetically isolate specific receptor-cofactor pairs in cells, allowing us to define the biological responses attributable to each complex. This is accomplished by using combinatorial peptide phage display to engineer the receptor interacting domain of each cofactor such that it interacts selectively with one nuclear receptor. In this study, we describe the customization of PGC-1alpha and its use to study the biology of the estrogen-related receptor alpha (ERRalpha) in cultured liver cells.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
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Cell Line, Tumor
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ERRalpha Estrogen-Related Receptor
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Enzymes / metabolism
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Fatty Acids / metabolism
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HeLa Cells
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Heat-Shock Proteins / chemistry
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Heat-Shock Proteins / metabolism*
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Hepatocytes / metabolism
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Humans
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Oxidation-Reduction
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Peptide Library
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Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
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RNA, Messenger / antagonists & inhibitors
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RNA, Small Interfering / pharmacology
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Receptors, Estrogen / antagonists & inhibitors
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Receptors, Estrogen / genetics
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Receptors, Estrogen / metabolism*
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Transcription Factors / chemistry
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Transcription Factors / metabolism*
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Tumor Cells, Cultured
Substances
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Enzymes
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Fatty Acids
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Heat-Shock Proteins
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PPARGC1A protein, human
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Peptide Library
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Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
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RNA, Messenger
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RNA, Small Interfering
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Receptors, Estrogen
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Transcription Factors