Document Detail


O-GlcNAc protein modification in cancer cells increases in response to glucose deprivation through glycogen degradation.
MedLine Citation:
PMID:  19833729     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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:
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
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-10-15
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  284     ISSN:  1083-351X     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  2009 Dec 
Date Detail:
Created Date:  2009-12-07     Completed Date:  2010-02-05     Revised Date:  2010-12-14    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  34777-84     Citation Subset:  IM    
Affiliation:
Department of Biology, Oral Cancer Research Institute, Korea.
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MeSH Terms
Descriptor/Qualifier:
AMP-Activated Protein Kinases / metabolism
Acetylglucosamine / metabolism*
Animals
Cell Line
Glucose / metabolism*
Glycogen / metabolism*
Humans
N-Acetylglucosaminyltransferases / metabolism
Neoplasms / metabolism*
Protein Processing, Post-Translational*
Chemical
Reg. No./Substance:
50-99-7/Glucose; 7512-17-6/Acetylglucosamine; 9005-79-2/Glycogen; EC 2.4.1.-/N-Acetylglucosaminyltransferases; EC 2.4.1.-/O-GlcNAc transferase; EC 2.7.11.1/AMP-Activated Protein Kinases

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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