Identification of PNRC2 and TLE1 as activation function-1 cofactors of the orphan nuclear receptor ERRgamma.
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.
Hentschke
Moritz
M
Zentrum für Molekulare Neurobiologie, Institut für Entwicklungsneurobiologie, Universität Hamburg, Martinistrasse 52, D-20246, Hamburg, Germany.
Borgmeyer
Uwe
U
D000818:Animals; D001665:Binding Sites; D001921:Brain / Q000378:metabolism*; D001923:Brain Chemistry; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D056970:Co-Repressor Proteins; D006801:Humans; D009687:Nuclear Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D018160:Receptors, Cytoplasmic and Nuclear / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011960:Receptors, Estrogen / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D017471:Receptors, Interferon / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins; D015534:Trans-Activators / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000502:physiology*; D015533:Transcriptional Activation
D056970:Co-Repressor Proteins; C490917:ESRRG protein, human; C086185:IFNGR2 protein, human; C490116:Ifngr2 protein, mouse; D009687:Nuclear Proteins; C437718:PNRC2 protein, human; D018160:Receptors, Cytoplasmic and Nuclear; D011960:Receptors, Estrogen; D017471:Receptors, Interferon; D011993:Recombinant Fusion Proteins; D012097:Repressor Proteins; C499043:TLE1 protein, human; D015534:Trans-Activators; D014157:Transcription Factors