title: 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.
authors.affiliation: Department of Cell Biology, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
authors.forename: Shiuh-Rong
authors.initials: SR
authors.lastname: Ho
authors.forename: Kai
authors.initials: K
authors.lastname: Wang
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Whisenhunt
authors.forename: Ping
authors.initials: P
authors.lastname: Huang
authors.forename: Xiaolin
authors.initials: X
authors.lastname: Zhu
authors.forename: Jeffrey E
authors.initials: JE
authors.lastname: Kudlow
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Paterson
mesh_terms: D000117:Acetylglucosamine / Q000378:metabolism*; D000215:Acylation; D018797:Cell Cycle Proteins; D002460:Cell Line; D051858:Forkhead Transcription Factors; D005786:Gene Expression Regulation; D006801:Humans; D017351:N-Acetylglucosaminyltransferases / Q000378:metabolism; D018384:Oxidative Stress / Q000235:genetics*; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic; D001619:beta-N-Acetylhexosaminidases / Q000378:metabolism
chemical_list: D018797:Cell Cycle Proteins; C108803:FOXO4 protein, human; D051858:Forkhead Transcription Factors; D014157:Transcription Factors; D017351:N-Acetylglucosaminyltransferases; C449880:O-GlcNAc transferase; C110628:hexosaminidase C; D001619:beta-N-Acetylhexosaminidases; D000117:Acetylglucosamine