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Current Signal Transduction Therapy


ISSN (Print): 1574-3624
ISSN (Online): 2212-389X

Protein O-GlcNAcylation: A Critical Regulator of the Cellular Response to Stress

Author(s): John C. Chatham and Richard B. Marchase

Volume 5, Issue 1, 2010

Page: [49 - 59] Pages: 11

DOI: 10.2174/157436210790226492

Price: $65


The post-translational modification of serine and threonine residues of nuclear and cytoplasmic proteins by the O-linked attachment of the monosaccharide ß-N-acetyl-glucosamine (O-GlcNAc) is a highly dynamic and ubiquitous protein modification that plays a critical role in regulating numerous biological processes. Much of our understanding of the mechanisms underlying the role of O-GlcNAc on cellular function has been in the context of chronic disease processes. However, there is increasing evidence that O-GlcNAc levels are increased in response to stress and that acute augmentation of this response is cytoprotective, at least in the short term. Conversely, a reduction in O-GlcNAc levels appears to be associated with decreased cell survival in response to an acute stress. Here we summarize our current understanding of protein O-GlcNAcylation on the cellular response to stress and in mediating cellular protective mechanisms focusing primarily on the cardiovascular system as an example. We consider the potential link between O-GlcNAcylation and cardiomyocyte calcium homeostasis and explore the parallels between O-GlcNAc signaling and redox signaling. We also discuss the apparent paradox between the reported adverse effects of increased O-GlcNAcylation with its recently reported role in mediating cell survival mechanisms.

Keywords: Hexosamine biosynthesis, protein O-glycosylation, capacitative calcium entry (CCE), oxidative stress, heart, ischemia

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