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PMID:12588810

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Citation

Puigserver, P and Spiegelman, BM (2003) Peroxisome proliferator-activated receptor-gamma coactivator 1 alpha (PGC-1 alpha): transcriptional coactivator and metabolic regulator. Endocr. Rev. 24:78-90

Abstract

Investigations of biological programs that are controlled by gene transcription have mainly studied the regulation of transcription factors. However, there are examples in which the primary focus of biological regulation is at the level of a transcriptional coactivator. We have reviewed here the molecular mechanisms and biological programs controlled by the transcriptional coactivator peroxisome proliferator-activated receptor-gamma coactivator 1 alpha (PGC-1 alpha). Key cellular signals that control energy and nutrient homeostasis, such as cAMP and cytokine pathways, strongly activate PGC-1 alpha. Once PGC-1 alpha is activated, it powerfully induces and coordinates gene expression that stimulates mitochondrial oxidative metabolism in brown fat, fiber-type switching in skeletal muscle, and multiple aspects of the fasted response in liver. The regulation of these metabolic and cell fate decisions by PGC-1 alpha is achieved through specific interaction with a variety of transcription factors such as nuclear hormone receptors, nuclear respiratory factors, and muscle-specific transcription factors. PGC-1 alpha therefore constitutes one of the first and clearest examples in which biological programs are chiefly regulated by a transcriptional coactivator in response to environmental stimuli. Finally, PGC-1 alpha's control of energy homeostasis suggests that it could be a target for anti-obesity or diabetes drugs.

Links

PubMed

Keywords

Acetyltransferases; Adipocytes; Animals; Cytokines; Energy Metabolism; Gene Expression; Gluconeogenesis; Histone Acetyltransferases; Homeostasis; Humans; Mitogen-Activated Protein Kinases/metabolism; Phosphorylation; Saccharomyces cerevisiae Proteins; Thermogenesis; Transcription Factors/physiology; p38 Mitogen-Activated Protein Kinases

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

HUMAN:PRGC1

located_in

GO:0005634: nucleus

ECO:0000304: author statement supported by traceable reference used in manual assertion

C

Seeded From UniProt

complete

HUMAN:PRGC1

enables

GO:0140297: DNA-binding transcription factor binding

ECO:0000304: author statement supported by traceable reference used in manual assertion

F

Seeded From UniProt

complete

HUMAN:PRGC1

enables

GO:0003723: RNA binding

ECO:0000304: author statement supported by traceable reference used in manual assertion

F

Seeded From UniProt

complete

HUMAN:PRGC1

part_of

GO:0005634: nucleus

ECO:0000304: author statement supported by traceable reference used in manual assertion

C

Seeded From UniProt

complete

HUMAN:PRGC1

involved_in

GO:0006397: mRNA processing

ECO:0000304: author statement supported by traceable reference used in manual assertion

P

Seeded From UniProt

complete

HUMAN:PRGC1

enables

GO:0008134: transcription factor binding

ECO:0000304: author statement supported by traceable reference used in manual assertion

F

Seeded From UniProt

complete

HUMAN:PRGC1

involved_in

GO:0008380: RNA splicing

ECO:0000304: author statement supported by traceable reference used in manual assertion

P

Seeded From UniProt

complete

HUMAN:PRGC1

involved_in

GO:0045722: positive regulation of gluconeogenesis

ECO:0000304: author statement supported by traceable reference used in manual assertion

P

Seeded From UniProt

complete

HUMAN:PRGC1

involved_in

GO:0046321: positive regulation of fatty acid oxidation

ECO:0000304: author statement supported by traceable reference used in manual assertion

P

Seeded From UniProt

complete

HUMAN:PRGC1

involved_in

GO:0050873: brown fat cell differentiation

ECO:0000304: author statement supported by traceable reference used in manual assertion

P

Seeded From UniProt

complete

HUMAN:PPARG

involved_in

GO:0050872: white fat cell differentiation

ECO:0000304: author statement supported by traceable reference used in manual assertion

P

Seeded From UniProt

complete


See also

References

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