期刊
CELL METABOLISM
卷 3, 期 6, 页码 429-438出版社
CELL PRESS
DOI: 10.1016/j.cmet.2006.04.013
关键词
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资金
- NIDDK NIH HHS [DK06627] Funding Source: Medline
Hormonal and nutrient regulation of hepatic gluconeogenesis mainly occurs through modulation of the transcriptional coactivator PGC-1 alpha. The identity of endogenous proteins and their enzymatic activities that regulate the functions and form part of PGC-1 alpha complex are unknown. Here, we show that PGC-1 alpha is in a multiprotein complex containing the acetyltransferase GCN5. PGC-1 alpha is directly acetylated by GCN5 resulting in a transcriptionally inactive protein that relocalizes from promoter regions to nuclear foci. Adenoviral-mediated expression of GCN5 in cultured hepatocytes and in mouse liver largely represses activation of gluconeogenic enzymes and decreases hepatic glucose production. Thus, we have identified the endogenous PGC-1 alpha protein complex and provided the molecular mechanism by which PGC-1 alpha acetylation by GCN5 turns off the transcriptional and biological function of this metabolic coactivator. GCN5 might be a pharmacological target to regulate the activity of PGC-1 alpha, providing a potential treatment for metabolic disorders in which hepatic glucose output is dysregulated.
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