Dynamic O-GlcNAcylation and its roles in the cellular stress response and homeostasis

Jennifer A. Groves, Albert Lee, Gokben Yildirir, Natasha E. Zachara

Research output: Contribution to journalReview articleResearchpeer-review

Abstract

O-linked N-acetyl-β-d-glucosamine (O-GlcNAc) is a ubiquitous and dynamic post-translational modification known to modify over 3,000 nuclear, cytoplasmic, and mitochondrial eukaryotic proteins. Addition of O-GlcNAc to proteins is catalyzed by the O-GlcNAc transferase and is removed by a neutral-N-acetyl-β-glucosaminidase (O-GlcNAcase). O-GlcNAc is thought to regulate proteins in a manner analogous to protein phosphorylation, and the cycling of this carbohydrate modification regulates many cellular functions such as the cellular stress response. Diverse forms of cellular stress and tissue injury result in enhanced O-GlcNAc modification, or O-GlcNAcylation, of numerous intracellular proteins. Stress-induced O-GlcNAcylation appears to promote cell/tissue survival by regulating a multitude of biological processes including: the phosphoinositide 3-kinase/Akt pathway, heat shock protein expression, calcium homeostasis, levels of reactive oxygen species, ER stress, protein stability, mitochondrial dynamics, and inflammation. Here, we will discuss the regulation of these processes by O-GlcNAc and the impact of such regulation on survival in models of ischemia reperfusion injury and trauma hemorrhage. We will also discuss the misregulation of O-GlcNAc in diseases commonly associated with the stress response, namely Alzheimer's and Parkinson's diseases. Finally, we will highlight recent advancements in the tools and technologies used to study the O-GlcNAc modification.

LanguageEnglish
Pages535-558
Number of pages24
JournalCell Stress and Chaperones
Volume18
Issue number5
DOIs
Publication statusPublished - Sep 2013
Externally publishedYes

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Homeostasis
Heat-Shock Proteins
Proteins
Mitochondrial Dynamics
Biological Phenomena
Hexosaminidases
Tissue Survival
1-Phosphatidylinositol 4-Kinase
Protein Stability
Mitochondrial Proteins
Glucosamine
Tissue
Wounds and Injuries
Post Translational Protein Processing
Reperfusion Injury
Phosphorylation
Parkinson Disease
Reactive Oxygen Species
Cell Survival
Alzheimer Disease

Cite this

Groves, Jennifer A. ; Lee, Albert ; Yildirir, Gokben ; Zachara, Natasha E. / Dynamic O-GlcNAcylation and its roles in the cellular stress response and homeostasis. In: Cell Stress and Chaperones. 2013 ; Vol. 18, No. 5. pp. 535-558.
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Dynamic O-GlcNAcylation and its roles in the cellular stress response and homeostasis. / Groves, Jennifer A.; Lee, Albert; Yildirir, Gokben; Zachara, Natasha E.

In: Cell Stress and Chaperones, Vol. 18, No. 5, 09.2013, p. 535-558.

Research output: Contribution to journalReview articleResearchpeer-review

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