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O-GlcNAcylation enhances FOXO4 transcriptional regulation in response to stress.


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.

SUBMITTER: Ho SR 

PROVIDER: S-EPMC2802345 | biostudies-literature | 2010 Jan

REPOSITORIES: biostudies-literature

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O-GlcNAcylation enhances FOXO4 transcriptional regulation in response to stress.

Ho Shiuh-Rong SR   Wang Kai K   Whisenhunt Thomas R TR   Huang Ping P   Zhu Xiaolin X   Kudlow Jeffrey E JE   Paterson Andrew J AJ  

FEBS letters 20100101 1


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 FOXO  ...[more]

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