The role of O-linked GlcNAc modification on the glucose response of ChREBP

Haruhiko Sakiyama, Noriko Fujiwara, Takahiro Noguchi, Hironobu Eguchi, Daisaku Yoshihara, Kosaku Uyeda, Keiichiro Suzuki

Research output: Contribution to journalArticle

36 Scopus citations

Abstract

The carbohydrate response element-binding protein (ChREBP) functions as a transcription factor in mediating the glucose-activated gene expression of multiple liver enzymes, which are responsible for converting excess carbohydrate to storage fat. ChREBP is translocated into the nucleus in response to high glucose levels, and then up-regulates transcriptional activity. Although this glucose activation of ChREBP is generally observed only in liver cells, overexpression of wild type max-like protein X (Mlx), but not an inactive mutant Mlx, resulted in the exhibition of the ChREBP functions also in a human kidney cell line. Because high glucose conditions induce the glycosylation of cellular proteins, the effect of O-linked GlcNAc modification on ChREBP functions was examined. Treatment with an O-GlcNAcase inhibitor (PUGNAc), which increases the O-linked GlcNAc modification of cellular proteins, caused an increase in the glucose response of ChREBP. In contrast, treatment with a glutamine fructose amidotransferase inhibitor (DON), which decreases O-GlcNAcylation by inhibiting the hexosamine biosynthetic pathway, completely blocked the glucose response of ChREBP. These results suggest that the O-linked glycosylation of ChREBP itself or other proteins that regulate ChREBP is essential for the production of functional ChREBP.

Original languageEnglish (US)
Pages (from-to)784-789
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume402
Issue number4
DOIs
Publication statusPublished - Nov 26 2010

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Keywords

  • ChREBP
  • Mlx
  • O-GlcNAc
  • Subcellular localization
  • Transcription factor

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Cell Biology
  • Molecular Biology

Cite this

Sakiyama, H., Fujiwara, N., Noguchi, T., Eguchi, H., Yoshihara, D., Uyeda, K., & Suzuki, K. (2010). The role of O-linked GlcNAc modification on the glucose response of ChREBP. Biochemical and Biophysical Research Communications, 402(4), 784-789. https://doi.org/10.1016/j.bbrc.2010.10.113