I. Tcherepanova et al., Modulation of estrogen receptor-alpha transcriptional activity by the coactivator PGC-1, J BIOL CHEM, 275(21), 2000, pp. 16302-16308
A transcriptional coactivator of the peroxisome proliferator-activated rece
ptor-gamma (PPAR gamma), PPAR gamma-coactivator-1(PGC-1) interacts in a con
stitutive manner with the hinge domain of PPAR gamma and enhances its trans
criptional activity. In this study we demonstrate that PGC-1 is a coactivat
or of estrogen receptor-alpha (ER alpha)-dependent transcriptional activity
. However the mechanism by which PGC-1 interacts with ER alpha is different
from that of PPAR gamma. Specifically, it was determined that the carboxyl
terminus of PGC-1 interacts in a ligand-independent manner with the ER alp
ha hinge domain. In addition, an LXXLL motif within the amino terminus of P
GC-1 was shown to interact in an agonist-dependent manner with the AF2 doma
in within the carboxyl terminus of ER alpha. The ability of PGC-1 to associ
ate with and potentiate the transcriptional activity of an ER alpha-AF2 mut
ant that is unable to interact with the p160 class of coactivators suggests
that this coactivator may have a unique role in estrogen signaling. It is
concluded from these studies that PGC-1 is a bona fide ER alpha coactivator
, which may serve as a convergence point between PPAR gamma and ER alpha si
gnaling.