O-GlcNAc protein modification in cancer cells increases in response to glucose deprivation through glycogen degradation

Jeong Gu Kang, Sang Yoon Park, Suena Ji, Insook Jang, Sujin Park, Hyun Sil Kim, Sung Min Kim, Jong In Yook, Yong Il Park, Jürgen Roth, Jin Won Cho

Research output: Contribution to journalArticlepeer-review

54 Citations (Scopus)

Abstract

When cellular glucose concentrations fall below normal levels, in general the extent of protein O-GlcNAc modification (O-GlcNAcylation) decreases. However, recent reports demonstrated increased O-GlcNAcylation by glucose deprivation in HepG2 and Neuro-2a cells. Here, we report increased O-GlcNAcylation in non-small cell lung carcinoma A549 cells and various other cells in response to glucose deprivation. Although the level of O-GlcNAc transferase was unchanged, the enzyme contained less O-GlcNAc, and its activity was increased. Moreover, O-GlcNAcase activity was reduced. The studied cells contain glycogen, and we show that its degradation in response to glucose deprivation provides a source for UDP-GlcNAc required for increased O-GlcNAcylation under this condition. This required active glycogen phosphorylase and resulted in increased glutamine:fructose-6-phosphate amidotransferase, the first and rate-limiting enzyme in the hexosamine biosynthetic pathway. Interestingly, glucose deprivation reduced the amount of phosphofructokinase 1, a regulatory glycolytic enzyme, and blocked ATP synthesis. These findings suggest that glycogen is the source for increased O-GlcNAcylation but not for generating ATP in response to glucose deprivation and that this may be useful for cancer cells to survive.

Original languageEnglish
Pages (from-to)34777-34784
Number of pages8
JournalJournal of Biological Chemistry
Volume284
Issue number50
DOIs
Publication statusPublished - 2009 Dec 11

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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