TY - JOUR
T1 - Modulation of estrogen receptor-α transcriptional activity by the coactivator PGC-1
AU - Tcherepanova, Irina
AU - Puigserver, Pere
AU - Norris, John D.
AU - Spiegelman, Bruce M.
AU - McDonnell, Donald P.
PY - 2000/5/26
Y1 - 2000/5/26
N2 - A transcriptional coactivator of the peroxisome proliferator-activated receptor-γ (PPARγ), PPARγ-coactivator-1(PGC-1) interacts in a constitutive manner with the hinge domain of PPARγ and enhances its transcriptional activity. In this study we demonstrate that PGC-1 is a coactivator of estrogen receptor-α (ERα)-dependent transcriptional activity. However the mechanism by which PGC-1 interacts with ERα is different from that of PPARγ. Specifically, it was determined that the carboxyl terminus of PGC-1 interacts in a ligand-independent manner with the ERα hinge domain. In addition, an LXXLL motif within the amino terminus of PGC-1 was shown to interact in an agonist-dependent manner with the AF2 domain within the carboxyl terminus of ERα. The ability of PGC-1 to associate with and potentiate the transcriptional activity of an ERα-AF2 mutant 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 ERα coactivator, which may serve as a convergence point between PPARγ and ERα signaling.
AB - A transcriptional coactivator of the peroxisome proliferator-activated receptor-γ (PPARγ), PPARγ-coactivator-1(PGC-1) interacts in a constitutive manner with the hinge domain of PPARγ and enhances its transcriptional activity. In this study we demonstrate that PGC-1 is a coactivator of estrogen receptor-α (ERα)-dependent transcriptional activity. However the mechanism by which PGC-1 interacts with ERα is different from that of PPARγ. Specifically, it was determined that the carboxyl terminus of PGC-1 interacts in a ligand-independent manner with the ERα hinge domain. In addition, an LXXLL motif within the amino terminus of PGC-1 was shown to interact in an agonist-dependent manner with the AF2 domain within the carboxyl terminus of ERα. The ability of PGC-1 to associate with and potentiate the transcriptional activity of an ERα-AF2 mutant 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 ERα coactivator, which may serve as a convergence point between PPARγ and ERα signaling.
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U2 - 10.1074/jbc.M001364200
DO - 10.1074/jbc.M001364200
M3 - Article
C2 - 10748020
AN - SCOPUS:0034717075
SN - 0021-9258
VL - 275
SP - 16302
EP - 16308
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 21
ER -