O-GlcNAcylation enhances FOXO4 transcriptional regulation in response to stress.
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.
Ho
Shiuh-Rong
SR
Department of Cell Biology, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
Wang
Kai
K
Whisenhunt
Thomas R
TR
Huang
Ping
P
Zhu
Xiaolin
X
Kudlow
Jeffrey E
JE
Paterson
Andrew J
AJ
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
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