Activation of PPARgamma coactivator-1 through transcription factor docking.
Transcriptional coactivators have been viewed as constitutively active components, using transcription factors mainly to localize their functions. Here, it is shown that PPARgamma coactivator-1 (PGC-1) promotes transcription through the assembly of a complex that includes the histone acetyltransferases steroid receptor coactivator-1 (SRC-1) and CREB binding protein (CBP)/p300. PGC-1 has a low inherent transcriptional activity when it is not bound to a transcription factor. The docking of PGC-1 to peroxisome proliferator-activated receptor gamma (PPARgamma) stimulates an apparent conformational change in PGC-1 that permits binding of SRC-1 and CBP/p300, resulting in a large increase in transcriptional activity. Thus, transcription factor docking switches on the activity of a coactivator protein.
Puigserver
P
P
Dana-Farber Cancer Institute and Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.
Adelmant
G
G
Wu
Z
Z
Fan
M
M
Xu
J
J
O'Malley
B
B
Spiegelman
B M
BM
D000818:Animals; D001665:Binding Sites; D019556:COS Cells; D004268:DNA-Binding Proteins / Q000378:metabolism; D050881:E1A-Associated p300 Protein; D005786:Gene Expression Regulation; D051548:Histone Acetyltransferases; D051379:Mice; D009687:Nuclear Proteins / Q000737:chemistry / Q000378:metabolism*; D056920:Nuclear Receptor Coactivator 1; D051264:Nuclear Respiratory Factors; D011485:Protein Binding; D011487:Protein Conformation; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D015534:Trans-Activators / Q000737:chemistry / Q000378:metabolism*; D014157:Transcription Factors / Q000737:chemistry / Q000378:metabolism*; D014158:Transcription, Genetic; D014162:Transfection
D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D051264:Nuclear Respiratory Factors; D018160:Receptors, Cytoplasmic and Nuclear; D011993:Recombinant Fusion Proteins; D015534:Trans-Activators; D014157:Transcription Factors; C111264:peroxisome-proliferator-activated receptor-gamma coactivator-1; D050881:E1A-Associated p300 Protein; C494361:Ep300 protein, mouse; D051548:Histone Acetyltransferases; C538861:Ncoa1 protein, mouse; D056920:Nuclear Receptor Coactivator 1