Biochemia Medica, Vol. 17 No. 2, 2007.
Review article
Protein-associated O-GIcNAc, a multifunctional mechanism in cell signaling and its role in the pathogenesis of diabetes, stress and malignant diseases
Tamas Nagy
Attila Miseta
Gabor L. Kovacs
Abstract
Growing evidence suggests that hexosamine biosynthesis pathway (HBP) plays a significant role in the modulation of intracellular signaling transduc-tion pathways. Its end product, UDP-GlcNAc is a substrate for the addition of O-linked β-N-acetylglucosamine (O-GlcNAc) to Ser/Thr residues. This process regulates a wide range of proteins usually by interfering with phosphoryla-tion. O-GlcNAc is a dynamic posttranslational modification, which is essential in normal mammalian cellular function; however, its main significance has been revealed in pathological processes. Since HBP requires glucose, high glucose intake considerably increases the flux through HBP and also increases the ratio of O-GlcNAc-associated proteins. This has an impact on various cellular functions, involving either the traditionally recognized detrimental effects in diabetes and diabetic complications or, as found recently, O-GlcNAc might be beneficial in ischemia/reperfusion injuries. In this review we summarize the current findings in O-GlcNAc research concerning its participation in signaling pathways and cellular processes. We also focus on the impact of O-GlcNAc in diseases such as diabetes, inflammation, development of malignancies or hypoxia-induced injuries.
Keywords
O-GlcNAc; Ca2+; diabetes; stress response; malignancy
Hrčak ID:
18131
URI
Publication date:
28.11.2007.
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