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Dynamic Intracellular Glycosylation: O‐GlcNAc, is a Key Modulator of Glutamine‐Mediated Cellular Protection and Heat Shock Protein 72 Induction
Author(s) -
Haserodt Sarah Kristen,
Pett Virginia,
Zachara Natasha E
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.648.3
Subject(s) - glutamine , heat shock protein , serine , intracellular , microbiology and biotechnology , glycosylation , phosphorylation , heat shock , biochemistry , knockout mouse , hsp70 , chemistry , biology , amino acid , gene
The enzyme O‐ GlcNAc transferase (OGT) dynamically modifies over 500 intracellular proteins by adding O‐ linked β‐ N‐ acetylglucosamine ( O ‐GlcNAc) to threonine and serine residues, regulating protein function in a manner analogous to protein phosphorylation. In response to numerous stressful stimuli, O‐GlcNAc attachment to proteins increases. Augmenting O‐GlcNAc modification prior to cellular injury improves cellular survival, suggesting that this is a pro‐survival response of cells. The mechanism by which O‐GlcNAc increases cellular survival is unknown. However, increased O‐GlcNAc correlates with the enhanced expression of heat shock protein 72 (HSP 72); in contrast, decreased O‐GlcNAc is associated with the reduced expression of HSP72. Interestingly, Glutamine is known to modulate both O‐GlcNAc and HSP72 levels, and supplementation with glutamine improves survival rates in both in vivo and in vitro models. In this study we have used Cre‐Lox technology to delete OGT and to determine if glutamine could modulate either cellular survival or the expression of HSP72. Our data show that in the OGT knockout, glutamine is not protective and can not alter HSP72 expression levels. Moreover, HSP72 induction is ablated in the OGT knockout. We are currently investigating the molecular mechanism by which O‐GlcNAc mediates the expression of HSP72 at the transcriptional level.