Identification of PNRC2 and TLE1 as activation function-1 cofactors of the orphan nuclear receptor ERRgamma
Hentschke, M.; Borgmeyer, U.
Biochemical and Biophysical Research Communications 312(4): 975-982
2003
ISSN/ISBN: 0006-291X PMID: 14651967 Document Number: 564391
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.