O-GlcNAc a sensor of cellular state: the role of nucleocytoplasmic glycosylation in modulating cellular function in response to nutrition and stress.
Myriad nuclear and cytoplasmic proteins in metazoans are modified on Ser and Thr residues by the monosaccharide O-linked beta-N-acetylglucosamine (O-GlcNAc). The rapid and dynamic change in O-GlcNAc levels in response to extracellular stimuli, morphogens, the cell cycle and development suggests a key role for O-GlcNAc in signal transduction pathways. Modulation of O-GlcNAc levels has profound effects on the functioning of cells, in part mediated through a complex interplay between O-GlcNAc and O-phosphate. In many well-studied proteins, the O-GlcNAc modification and phosphorylation are reciprocal. That is, they occur on different subsets of the protein population, as the site of attachment occurs on the same or adjacent Ser/Thr residues. Recently, O-GlcNAc has been implicated in the etiology of type II diabetes, the regulation of stress response pathways, and in the regulation of the proteasome.
Zachara
Natasha E
NE
Department of Biological Chemistry, The Johns Hopkins University School of Medicine, 725 N. Wolfe Street, Baltimore, MD 21205-2185, USA.
Hart
Gerald W
GW
D000117:Acetylglucosamine / Q000378:metabolism*; D000118:Acetylglucosaminidase / Q000378:metabolism*; D000818:Animals; D016923:Cell Death; D002467:Cell Nucleus / Q000378:metabolism*; D003593:Cytoplasm / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000209:etiology; D005947:Glucose / Q000378:metabolism; D006031:Glycosylation; D051548:Histone Acetyltransferases; D006801:Humans; D009097:Multienzyme Complexes; D009747:Nutritional Physiological Phenomena; D010766:Phosphorylation; D011506:Proteins / Q000378:metabolism*; D015398:Signal Transduction; D013312:Stress, Physiological / Q000378:metabolism; D001619:beta-N-Acetylhexosaminidases
D009097:Multienzyme Complexes; D011506:Proteins; D051548:Histone Acetyltransferases; C110628:hexosaminidase C; D000118:Acetylglucosaminidase; D001619:beta-N-Acetylhexosaminidases; D005947:Glucose; D000117:Acetylglucosamine