RGD Reference Report - New insights into metabolic signaling and cell survival: the role of beta-O-linkage of N-acetylglucosamine. - Rat Genome Database

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New insights into metabolic signaling and cell survival: the role of beta-O-linkage of N-acetylglucosamine.

Authors: Ngoh, GA  Jones, SP 
Citation: Ngoh GA and Jones SP, J Pharmacol Exp Ther. 2008 Dec;327(3):602-9. Epub 2008 Sep 3.
RGD ID: 5130015
Pubmed: PMID:18768779   (View Abstract at PubMed)
PMCID: PMC6545568   (View Article at PubMed Central)
DOI: DOI:10.1124/jpet.108.143263   (Journal Full-text)

The involvement of glucose in fundamental metabolic pathways represents a core element of biology. Late in the 20th century, a unique glucose-derived signal was discovered, which appeared to be involved in a variety of cellular processes, including mitosis, transcription, insulin signaling, stress responses, and potentially, Alzheimer's disease, and diabetes. By definition, this glucose-fed signaling system was a post-translational modification to proteins. However, unlike classical cotranslational N-glycosylation occurring in the endoplasmic reticulum and Golgi apparatus, this process occurs elsewhere throughout the cell in a highly dynamic fashion, similar to the quintessential post-translational modification, phosphorylation. This more recently described post-translational modification, the beta-O-linkage of N-acetylglucosamine (i.e., O-GlcNAc) to nucleocytoplasmic proteins, represents an under-investigated area of biology. This signaling system operates in all of the tissues examined and seems to have persisted throughout all multicellular eukaryotes. Thus, it comes with little surprise that O-GlcNAc signaling is an integral system and viable target for biomedical investigation. This system may be a boundless source for insight into a variety of diseases and yield numerous opportunities for drug design. This Perspective will address recent insights into O-GlcNAc signaling in the cardiovascular system as a paradigm for its involvement in other biological systems.


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