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Front Endocrinol (Lausanne). 2018 Oct 16;9:599. doi: 10.3389/fendo.2018.00599. eCollection 2018.

O-GlcNAc as an Integrator of Signaling Pathways.

Ong Q1,2,3,4, Han W4, Yang X1,2,3.

Author information

1
Department of Comparative Medicine, Yale University School of Medicine, New Haven, CT, United States.
2
Program in Integrative Cell Signaling and Neurobiology of Metabolism, Yale University School of Medicine, New Haven, CT, United States.
3
Department of Cellular and Molecular Physiology, Yale University School of Medicine, New Haven, CT, United States.
4
Laboratory of Metabolic Medicine, Singapore Bioimaging Consortium, Agency for Science, Technology and Research (ASTAR), Singapore, Singapore.

Abstract

O-GlcNAcylation is an important posttranslational modification governed by a single pair of enzymes-O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA). These two enzymes mediate the dynamic cycling of O-GlcNAcylation on a wide variety of cytosolic, nuclear and mitochondrial proteins in a nutrient- and stress-responsive fashion. While cellular functions of O-GlcNAcylation have been emerging, little is known regarding the precise mechanisms how the enzyme pair senses the environmental cues to elicit molecular and physiological changes. In this review, we discuss how the OGT/OGA pair acts as a metabolic sensor that integrates signaling pathways, given their capability of receiving signaling inputs from various partners, targeting multiple substrates with spatiotemporal specificity and translocating to different parts of the cell. We also discuss how the pair maintains homeostatic signaling within the cell and its physiological relevance. A better understanding of the mechanisms of OGT/OGA action would enable us to derive therapeutic benefits of resetting cellular O-GlcNAc levels within an optimal range.

KEYWORDS:

O-GlcNAc transferase; O-GlcNAcase; O-GlcNAcylation; homeostasis; metabolic sensor; posttranslational modification; signaling integrator; spatiotemporal dynamics

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