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LCBB, NIDDK, National Institutes of Health, Bethesda, Maryland 20892, USA
1Correspondence: Chief, LCBB, NIDDK, National Institutes of Health, Bldg. 8, Rm. 402, Bethesda, MD 20892, USA. E-mail: jah{at}helix.nih.gov
The addition of O-linked N-acetylglucosamine (O-GlcNAc) to target proteins may serve as a signaling modification analogous to protein phosphorylation. Like phosphorylation, O-GlcNAc is a dynamic modification occurring in the nucleus and cytoplasm. Various analytical methods have been developed to detect O-GlcNAc and distinguish it from glycosylation in the endomembrane system. Many target molecules have been identified; these targets are typically components of supramolecular complexes such as transcription factors, nuclear pore proteins, or cytoskeletal components. The enzymes responsible for O-GlcNAc addition and removal are highly conserved molecules having molecular features consistent with a signaling role. The O-GlcNAc transferase and O-GlcNAcase are likely to act in consort with kinases and phosphatases generating various isoforms of physiological substrates. These isoforms may differ in such properties as protein–protein interactions, protein stability, and enzymatic activity. Since O-GlcNAc plays a critical role in the regulation of signaling pathways of higher plants, the glycan modification is likely to perform similar signaling functions in mammalian cells. Glucose and amino acid metabolism generates hexosamine precursors that may be key regulators of a nutrient sensing pathway involving O-GlcNAc signaling. Altered O-linked GlcNAc metabolism may also occur in human diseases including neurodegenerative disorders, diabetes mellitus and cancer.—Hanover, J. A. Glycan-dependent signaling: O-linked N-acetylglucosamine.
Key Words: O-GlcNAc • hexosaminidase C • diabetes mellitus • OGT
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