O-GlcNAcylation enhances FOXO4 transcriptional regulation in response to stress

Ho, Shiuh-Rong; Wang, Kai; Whisenhunt, Thomas R.; Huang, Ping; Zhu, Xiaolin; Kudlow, Jeffrey E.; Paterson, Andrew J.

doi:10.1016/j.febslet.2009.11.059

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Volume 584, Issue 1 , Pages 49-54, 4 January 2010

O-GlcNAcylation enhances FOXO4 transcriptional regulation in response to stress

Edited by Quan Chen

Shiuh-Rong Ho
- Department of Cell Biology, University of Alabama at Birmingham, Birmingham, AL 35294, USA
Kai Wang
- Department of Medicine, Division of Endocrinology, Diabetes and Metabolism, University of Alabama at Birmingham, Birmingham, AL 35294, USA
Thomas R. Whisenhunt
- Department of Cell Biology, University of Alabama at Birmingham, Birmingham, AL 35294, USA
Ping Huang
- Department of Pharmacology and Toxicology, University of Alabama at Birmingham, Birmingham, AL 35294, USA
Xiaolin Zhu
- Department of Cell Biology, University of Alabama at Birmingham, Birmingham, AL 35294, USA
Jeffrey E. Kudlow
- Department of Cell Biology, University of Alabama at Birmingham, Birmingham, AL 35294, USA
- Department of Medicine, Division of Endocrinology, Diabetes and Metabolism, University of Alabama at Birmingham, Birmingham, AL 35294, USA
- Department of Pharmacology and Toxicology, University of Alabama at Birmingham, Birmingham, AL 35294, USA
- Department of Physiology and Biophysics, University of Alabama at Birmingham, Birmingham, AL 35294, USA
Andrew J. Paterson
- Department of Cell Biology, University of Alabama at Birmingham, Birmingham, AL 35294, USA
- Department of Medicine, Division of Endocrinology, Diabetes and Metabolism, University of Alabama at Birmingham, Birmingham, AL 35294, USA
- Department of Physiology and Biophysics, University of Alabama at Birmingham, Birmingham, AL 35294, USA
- Corresponding author. Address: Department of Cell Biology, University of Alabama at Birmingham, Birmingham, AL 35294, USA. Fax: +1 205 934 4389.

Received 10 August 2009; received in revised form 30 October 2009; accepted 15 November 2009. published online 20 November 2009.

Abstract

The FOXO4 transcription factor plays an important role in cell survival in response to oxidative stress. The regulation of FOXO4 is orchestrated by post-translational modifications including phosphorylation, acetylation, and ubiquitination. Here, we demonstrate that O-GlcNAcylation also contributes to the FOXO4-dependent oxidative stress response. We show that hydrogen peroxide treatment of HEK293 cells increases FOXO4 association with OGT, the enzyme that adds O-GlcNAc to proteins, causing FOXO4 O-GlcNAcylation and enhanced transcriptional activity under acute oxidative stress. O-GlcNAcylation is known to be protective for cells under stress conditions, including oxidative stress. Our data provide a mechanism of FOXO4 anti-oxidative protection through O-GlcNAcylation.

Structured summary

MINT-7299700, MINT-7299716: Foxo4 (uniprotkb:Q9WVH3) physically interacts (MI:0915) with Ogt (uniprotkb:P56558) by anti tag coimmunoprecipitation (MI:0007)

MINT-7299691: Ogt (uniprotkb:O15294) physically interacts (MI:0915) with Foxo4 (uniprotkb:P98177) by anti bait coimmunoprecipitation (MI:0006)

Keywords: OGT, NCOAT, Hydrogen peroxide, O-GlcNAc, p27^Kip1