PGC-1, a novel brown fat PPAR.gamma. coactivator

Details PGC-1, a novel brown fat PPAR.gamma. coactivator PGC-1, a novel brown fat PPAR.gamma. coactivator

1998-05-29

2000-12-26

Scheiner, Laurie

Organic compounds -- part of the class 532-570 series

Organic compounds

Carbohydrates or derivatives

536 234, 435 691, 4352523, C07H 2104

Patent

active

061661929

ABSTRACT:
The invention provides isolated nucleic acids molecules, designated PGC-1 nucleic acid molecules, which encode proteins which can modulate various adipocyte-associated activities including, for example, thermogenesis in adipocytes, e.g., brown adipocytes, and adipogenesis. The invention also provides antisense nucleic acid molecules, recombinant expression vectors containing PGC-1 nucleic acid molecules, host cells into which the expression vectors have been introduced, and nonhuman transgenic animals in which a PGC-1 gene has been introduced or disrupted. The invention still further provides isolated PGC-1 proteins, fusion proteins, antigenic peptides and anti-PGC-1 antibodies. Diagnostic, screening, and therapeutic methods utilizing compositions of the invention are also provided.

REFERENCES:
Heery et al. (1997) "A signature motif in transcriptional co-activators mediates binding to nuclear receptors". Nature 387:733-736.
Torchia et al. (1997) "The transcriptional co-activator p/CIP binds CBP and mediates nuclear-receptor function". Nature 387:677-684.
Yuryev et al. (1996) "The C-terminal domain of the largest subunit of RNA polymerase II interacts with a novel set of serine/arginine-rich proteins.". Proc. Natl. Acad. Sci. USA 93:6975-6980.
GenBank Accession No: AA107666; Feb. 4, 1997.
GenBank Accession No: AA188859; Jan. 13, 1997.
GenBank Accession No: AA242576; Mar. 7, 1997.
GenBank Accession No: AA388127; Apr. 23, 1997.
GenBank Accession No: AA388152; Apr. 23, 1997.
GenBank Accession No: AA413411; May 7, 1997.
GenBank Accession No: AA673291; Nov. 26, 1997.
GenBank Accession No: AA865326; Mar. 12, 1998.
GenBank Accession No: AI059434; Feb. 11, 1999.
GenBank Accession No:AI137178; Feb. 11, 1999.
Brun, R.P. et al. "Adipocyte Differentiation: a Transcritional Regulatory Cascade" Current Opinion in Cell Biology 8:826-832 (1996).
Cavailles, V. et al. "Nuclear Factor RIP140 Modulates Transcriptional Activation by the Estrogen Receptor" The EMBO Journal 14(15):3741-3751 (1995).
Chakravarti, D. et al. "Role of CBP/P300 in Nuclear Receptor Signalling" Nature 383:99-103 (1996).
Chen, H. et al. "Nuclear Receptor Coactibator ACTR is a Novel Histone Acetyltransferase and Forms a Multimeric Activation Complex with P/CAF and CBP/p300" Cell 90:569-580 (1997).
DiRenzo, J. et al. "Peroxisome Proliferator-Activated Receptors and Retinoic Acid Receptors Differentially Control the Interactions of Retinoid X Receptor Heterodimers with Ligands, Coactivators, and Corepressors" Molecular and Cellular Biology 17(4):2166-2176 (1997).
Flier, J.S. and Lowell, B.B. "Obesity Research Springs a Proton Leak" Nature Genetics 15:223-224 (1997).
Himms-Hagen, J. "Role of Thermogeniesis in the Regulation of Energy Balance in Relation to Obecity" Can. J. Physiol. Pharmacol. 67:374-401 (1989).
Hu, E. et al. "Inhibition of Adipogenesis Through MAP Kinase-Mediated Phosphorylation of PPAR.gamma." Science: Reprint Series:274:2100-2103 (1996).
Kamei, Y. et al. "A CBO Integrator Complex Mediates Transcriptional Activation and AP-1 Inhibition by Nuclear Receptors" Cell 85:403-414 (1996).
Kliewer, S.A. et al. "Fatty Acids and Eicosanoids Regulate Gene Expression Through Direct Interations with Peroxisome Proliferator-activated Receptors .alpha. and .gamma." Proc. Natl. Acad. Sci. USA 94:4318-4323 (1997).
Onate, S.A. et al. "Sequence and charachterization of a Coactivator for the Steroid Hormone Receptor Superfamily" Science 270:1354-1356 (1995).
Pillar, T.M. and Seitz, H.J. "Thyroid Hormone and Gene Expression in the Regulation of Mitochondrial Respiratory Function" European Journal of Endocrinology 136:231-239 (1997).
Puigserver, P. et al. "A Cold-Inducible Coactivator of Nuclear Receptors Linked to Adaptive Thermogenesis" Cell 92:829-839 (1998).
Sears, I.B. et al. "Differentiation-Dependent Expression of the Brown Adipocyte Uncoupling Protein Gene: Regulation by Peroxisome Proliferator-Activated Receptor .gamma." Molecular and Cellular Biology 16:(7):3410-3419 (1996).
Spiegelman, B.M. and Flier, J.S. "Adipogenesis and Obesity: Rounding Out the Big Picture" Cell 87:377-389 (1996).
Tontonoz, P. et al. "Stimulation of Adipogenesis in Firoblasts by PPAR.gamma.2, a Lipid-Activated Transcription Factor" Cell 79:1147-1156 (1994).
Voegel, J.J. et al. "TIF2, a 160 kDa Transcriptional Mediator for the Ligand-Dependent Activation Function AF-2 of Nuclear Receptors" The EMBO Journal 15(14):3667-3675 (1996).
Zhu, Y. et al. "Cloning and Identification of Mouse Steroid Receptor Coactivator-1 (mSRC-1), as a Coactivator of Peroxisome Proliferator-Activated Receptor .gamma." Gene Expression 6:185-195 (1996).
Zhu, Y. et al. "Isolation and Characterization of PBP, a Protein That Interacts with Peroxisome Proliferator-Acitvated Receptor" The Journal of Biological Chemistry 272(41):25500-25506 (1997).

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