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Science 12 November 1999:
Vol. 286. no. 5443, pp. 1368 - 1371
DOI: 10.1126/science.286.5443.1368
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Reports

Activation of PPARgamma Coactivator-1 Through Transcription Factor Docking

Pere Puigserver, 1 Guillaume Adelmant, 1 Zhidan Wu, 1 Melina Fan, 1 Jianming Xu, 2 Bert O'Malley, 2 Bruce M. Spiegelman 1*

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.

1 Dana-Farber Cancer Institute and Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.
2 Department of Cell Biology, Baylor College of Medicine, Houston, TX 77040, USA.
*   To whom correspondence should be addressed. E-mail: bruce_spiegelman{at}dfci.harvard.edu

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Cold Spring Harb Symp Quant Biol 67, 339-344
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Potentiation of Glucose Uptake in 3T3-L1 Adipocytes by PPAR{gamma} Agonists Is Maintained in Cells Expressing a PPAR{gamma} Dominant-Negative Mutant: Evidence for Selectivity in the Downstream Responses to PPAR{gamma} Activation.
C. Nugent, J. B. Prins, J. P. Whitehead, D. Savage, J. M. Wentworth, V. K. Chatterjee, and S. O'Rahilly (2001)
Mol. Endocrinol. 15, 1729-1738
   Abstract »    Full Text »    PDF »
Mechanisms of Estrogen Action.
S. Nilsson, S. Makela, E. Treuter, M. Tujague, J. Thomsen, G. Andersson, E. Enmark, K. Pettersson, M. Warner, and J.-A. Gustafsson (2001)
Physiol Rev 81, 1535-1565
   Abstract »    Full Text »    PDF »
Regulation of the transcriptional coactivator PGC-1 via MAPK-sensitive interaction with a repressor.
D. Knutti, D. Kressler, and A. Kralli (2001)
PNAS
   Abstract »    Full Text »    PDF »
Nuclear Hormone Receptors and Gene Expression.
A. Aranda and A. Pascual (2001)
Physiol Rev 81, 1269-1304
   Abstract »    Full Text »    PDF »
Development of Peptide Antagonists That Target Estrogen Receptor {beta}-Coactivator Interactions.
J. M. Hall, C.-y. Chang, and D. P. McDonnell (2000)
Mol. Endocrinol. 14, 2010-2023
   Abstract »    Full Text »
The Role of CBP in Estrogen Receptor Cross-Talk with Nuclear Factor-{kappa}B in HepG2 Cells.
D. C. Harnish, M. S. Scicchitano, S. J. Adelman, C. R. Lyttle, and S. K. Karathanasis (2000)
Endocrinology 141, 3403-3411
   Abstract »    Full Text »    PDF »
Histone Binding Protein RbAp48 Interacts with a Complex of CREB Binding Protein and Phosphorylated CREB.
Q. Zhang, N. Vo, and R. H. Goodman (2000)
Mol. Cell. Biol. 20, 4970-4978
   Abstract »    Full Text »
Artificial Recruitment of TFIID, but Not RNA Polymerase II Holoenzyme, Activates Transcription in Mammalian Cells.
D. R. Dorris and K. Struhl (2000)
Mol. Cell. Biol. 20, 4350-4358
   Abstract »    Full Text »
Transcriptional regulation of adipogenesis.
E. D. Rosen, C. J. Walkey, P. Puigserver, and B. M. Spiegelman (2000)
Genes & Dev. 14, 1293-1307
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Ligand type-specific Interactions of Peroxisome Proliferator-activated Receptor gamma with Transcriptional Coactivators.
Y. Kodera, K.-i. Takeyama, A. Murayama, M. Suzawa, Y. Masuhiro, and S. Kato (2000)
J. Biol. Chem. 275, 33201-33204
   Abstract »    Full Text »    PDF »
A Zebrafish Ftz-F1 (Fushi Tarazu Factor 1) Homologue Requires Multiple Subdomains in the D and E Regions for Its Transcriptional Activity.
D. Liu, M. Chandy, S.-K. Lee, Y. Le Drean, H. Ando, F. Xiong, J. Woon Lee, and C. L. Hew (2000)
J. Biol. Chem. 275, 16758-16766
   Abstract »    Full Text »    PDF »
Functional Interaction between the Mouse Notch1 Intracellular Region and Histone Acetyltransferases PCAF and GCN5.
H. Kurooka and T. Honjo (2000)
J. Biol. Chem. 275, 17211-17220
   Abstract »    Full Text »    PDF »
Transcriptional Activation of the Human ucp1 Gene in a Rodent Cell Line. SYNERGISM OF RETINOIDS, ISOPROTERENOL, AND THIAZOLIDINEDIONE IS MEDIATED BY A MULTIPARTITE RESPONSE ELEMENT.
M. del Mar Gonzalez-Barroso, C. Pecqueur, C. Gelly, D. Sanchis, M.-C. Alves-Guerra, F. Bouillaud, D. Ricquier, and A.-M. Cassard-Doulcier (2000)
J. Biol. Chem. 275, 31722-31732
   Abstract »    Full Text »    PDF »
Peroxisome Proliferator-activated Receptor alpha Activates Transcription of the Brown Fat Uncoupling Protein-1 Gene. A LINK BETWEEN REGULATION OF THE THERMOGENIC AND LIPID OXIDATION PATHWAYS IN THE BROWN FAT CELL.
M. J. Barbera, A. Schluter, N. Pedraza, R. Iglesias, F. Villarroya, and M. Giralt (2001)
J. Biol. Chem. 276, 1486-1493
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Role of Accessory Factors and Steroid Receptor Coactivator 1 in the Regulation of Phosphoenolpyruvate Carboxykinase Gene Transcription by Glucocorticoids.
J. M. Stafford, M. Waltner-Law, and D. K. Granner (2001)
J. Biol. Chem. 276, 3811-3819
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Transcriptional Regulation of the Mouse Uncoupling Protein-2 Gene. DOUBLE E-BOX MOTIF IS REQUIRED FOR PEROXISOME PROLIFERATOR-ACTIVATED RECEPTOR-gamma -DEPENDENT ACTIVATION.
A. V. Medvedev, S. K. Snedden, S. Raimbault, D. Ricquier, and S. Collins (2001)
J. Biol. Chem. 276, 10817-10823
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Small Heterodimer Partner, an Orphan Nuclear Receptor, Augments Peroxisome Proliferator-activated Receptor gamma Transactivation.
H. Nishizawa, K. Yamagata, I. Shimomura, M. Takahashi, H. Kuriyama, K. Kishida, K. Hotta, H. Nagaretani, N. Maeda, M. Matsuda, et al. (2002)
J. Biol. Chem. 277, 1586-1592
   Abstract »    Full Text »    PDF »


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