Stress-Induced O-GlcNAcylation, an Adaptive Process of Injured Cells

Abstract

In the 30 years since the discovery of nucleocytoplasmic glycosylation, O-GlcNAc has been implicated in regulating cellular processes as diverse as protein folding, localization, degradation, activity, post-translational modifications, and interactions. The cell coordinates these molecular events, on thousands of cellular proteins, in concert with environmental and physiological cues to fine-tune epigenetics, transcription, translation, signal transduction, cell cycle, and metabolism. The cellular stress response is no exception: diverse forms of injury result in dynamic changes to the O-GlcNAc sub-proteome that promote survival. In this review, we discuss the biosynthesis of O-GlcNAc, the mechanisms by which O-GlcNAc promotes cytoprotection, and the clinical significance of these data.

Summary Statement

Protein modification by the sugar O-GlcNAc is elevated following injury, including heart attack. This increase promotes survival. This review describes the current understanding of the mechanisms by which O-GlcNAc protects cells during stress and injury and discusses the clinical implications of these data.