Receptor-Selective Coactivators as Tools to Define the Biology of Specific Receptor-Coactivator Pairs

Stéphanie Gaillard, Linda L. Grasfeder, Christiane L. Haeffele, Edward K. Lobenhofer, Tzu Ming Chu, Russ Wolfinger, Dmitri Kazmin, Timothy R. Koves, Deborah M. Muoio, Ching yi Chang, Donald P. McDonnell

Research output: Contribution to journalArticlepeer-review

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-1α and its use to study the biology of the estrogen-related receptor α (ERRα) in cultured liver cells.

Original languageEnglish (US)
Pages (from-to)797-803
Number of pages7
JournalMolecular cell
Volume24
Issue number5
DOIs
StatePublished - Dec 8 2006
Externally publishedYes

Keywords

  • DNA
  • SIGNALING

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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