A PGC-1alpha-O-GlcNAc Transferase Complex Regulates FoxO Transcription Factor Activity in Response to Glucose

Overview

Journal J Biol Chem

Specialty Biochemistry

Date 2008 Dec 24

PMID 19103600

Citations 118

Authors

Michael P Housley

Namrata D Udeshi

Joseph T Rodgers

Jeffrey Shabanowitz

Pere Puigserver

Donald F Hunt

Gerald W Hart

Affiliations

Soon will be listed here.

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.

Citing Articles

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