O-GlcNAcylation enhances FOXO4 transcriptional regulation in response to stress

Academic Article

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). © 2009 Federation of European Biochemical Societies.
  • Published In

  • FEBS Letters  Journal
  • Digital Object Identifier (doi)

    Author List

  • Ho SR; Wang K; Whisenhunt TR; Huang P; Zhu X; Kudlow JE; Paterson AJ
  • Start Page

  • 49
  • End Page

  • 54
  • Volume

  • 584
  • Issue

  • 1