title: O-GlcNAc protein modification in cancer cells increases in response to glucose deprivation through glycogen degradation.
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.
authors.affiliation: Department of Biology, Oral Cancer Research Institute, Korea.
authors.forename: Jeong Gu
authors.initials: JG
authors.lastname: Kang
authors.forename: Sang Yoon
authors.initials: SY
authors.lastname: Park
authors.forename: Suena
authors.initials: S
authors.lastname: Ji
authors.forename: Insook
authors.initials: I
authors.lastname: Jang
authors.forename: Sujin
authors.initials: S
authors.lastname: Park
authors.forename: Hyun Sil
authors.initials: HS
authors.lastname: Kim
authors.forename: Sung-Min
authors.initials: SM
authors.lastname: Kim
authors.forename: Jong In
authors.initials: JI
authors.lastname: Yook
authors.forename: Yong-Il
authors.initials: YI
authors.lastname: Park
authors.forename: Jürgen
authors.initials: J
authors.lastname: Roth
authors.forename: Jin Won
authors.initials: JW
authors.lastname: Cho
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D000117:Acetylglucosamine / Q000378:metabolism*; D000818:Animals; D002460:Cell Line; D005947:Glucose / Q000378:metabolism*; D006003:Glycogen / Q000378:metabolism*; D006801:Humans; D017351:N-Acetylglucosaminyltransferases / Q000378:metabolism; D009369:Neoplasms / Q000378:metabolism*; D011499:Protein Processing, Post-Translational
chemical_list: D006003:Glycogen; D017351:N-Acetylglucosaminyltransferases; C449880:O-GlcNAc transferase; D055372:AMP-Activated Protein Kinases; D005947:Glucose; D000117:Acetylglucosamine