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J Biol Chem. 2009 Feb 20;284(8):5148-57. doi: 10.1074/jbc.M808890200. Epub 2008 Dec 22.

A PGC-1alpha-O-GlcNAc transferase complex regulates FoxO transcription factor activity in response to glucose.

Author information

  • 1Department of Biological Chemistry, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.

Abstract

Metabolic and stress response gene regulation is crucial for the survival of an organism to a changing environment. Three key molecules that sense nutrients and broadly affect gene expression are the FoxO transcription factors, the transcriptional co-activator PGC-1alpha, and the dynamic post-translational modification, O-linked beta-N-acetylglucosamine (O-GlcNAc). Here we identify novel post-translational modifications of PGC-1alpha, including O-GlcNAc, and describe a novel mechanism for how PGC-1alpha co-activates transcription by FoxOs. In liver, in cultured cells, and in vitro with recombinant proteins, PGC-1alpha binds to O-GlcNAc transferase and targets the enzyme to FoxOs, resulting in their increased GlcNAcylation and increased transcriptional activity. Furthermore, glucose-enhanced activation of FoxO1 occurs via this PGC-1alpha-O-GlcNAc transferase-mediated GlcNAcylation. Therefore, one mechanism by which PGC-1alpha can serve as a co-activator of transcription is by targeting the O-GlcNAc transferase to increase GlcNAcylation of specific transcription factors important to nutrient/stress sensing and energy metabolism.

PMID:
19103600
[PubMed - indexed for MEDLINE]
PMCID:
PMC2643526
Free PMC Article

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