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Sci. STKE, 29 November 2005
Vol. 2005, Issue 312, p. re13
[DOI: 10.1126/stke.3122005re13]
REVIEWS
The Hexosamine Signaling Pathway: Deciphering the "O-GlcNAc Code"
Dona C. Love and
John A. Hanover*
Laboratory of Cell Biochemistry and Biology, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD 20892, USA.
Gloss: Glycosylation is not usually considered a "signaling" modification. However, a dynamic cycle of addition and removal of O-linked N-acetylglucosamine (O-GlcNAc) at serine and threonine residues is emerging as a key regulator of nuclear and cytoplasmic protein activity. More than a hundred proteins have been identified with this modification. Among these diverse targets are transcription factors, cytosolic enzymes, cytoskeletal proteins, and nuclear pore proteins. Like phosphorylation, this unique modification is dynamic and reversible, serving to either enhance or repress target protein activity. Most targets are also phosphoproteins, and the action of glycosylation and phosphorylation may be complementary or mutually exclusive. Whereas phosphorylation is controlled by many unique kinases and phosphatases, O-GlcNAc cycling is controlled by the efficient use of just two genes to produce differentially targeted enzymes. These enzymes are responsive to fluctuations in nutrient stores, allowing real-time control of signaling. This review will begin to answer how the enzymes of O-GlcNAc cycling are regulated and how the cycle may interface with other cellular signaling pathways.
Reduced O-GlcNAcylation links lower brain glucose metabolism and tau pathology in Alzheimer's disease.
F. Liu, J. Shi, H. Tanimukai, J. Gu, J. Gu, I. Grundke-Iqbal, K. Iqbal, and C.-X. Gong (2009)
Brain
132, 1820-1832
|Abstract »|Full Text »|PDF »
Identification of protein O-GlcNAcylation sites using electron transfer dissociation mass spectrometry on native peptides.
R. J. Chalkley, A. Thalhammer, R. Schoepfer, and A. L. Burlingame (2009)
PNAS
106, 8894-8899
|Abstract »|Full Text »|PDF »
A PGC-1{alpha}-O-GlcNAc Transferase Complex Regulates FoxO Transcription Factor Activity in Response to Glucose.
M. P. Housley, N. D. Udeshi, J. T. Rodgers, J. Shabanowitz, P. Puigserver, D. F. Hunt, and G. W. Hart (2009)
J. Biol. Chem.
284, 5148-5157
|Abstract »|Full Text »|PDF »
Up-regulation of O-GlcNAc Transferase with Glucose Deprivation in HepG2 Cells Is Mediated by Decreased Hexosamine Pathway Flux.
R. P. Taylor, T. S. Geisler, J. H. Chambers, and D. A. McClain (2009)
J. Biol. Chem.
284, 3425-3432
|Abstract »|Full Text »|PDF »
Site-Specific GlcNAcylation of Human Erythrocyte Proteins: Potential Biomarker(s) for Diabetes.
Z. Wang, K. Park, F. Comer, L. C. Hsieh-Wilson, C. D. Saudek, and G. W. Hart (2009)
Diabetes
58, 309-317
|Abstract »|Full Text »|PDF »
Glucosamine improves cardiac function following trauma-hemorrhage by increased protein O-GlcNAcylation and attenuation of NF-{kappa}B signaling.
L. Zou, S. Yang, V. Champattanachai, S. Hu, I. H. Chaudry, R. B. Marchase, and J. C. Chatham (2009)
Am J Physiol Heart Circ Physiol
296, H515-H523
|Abstract »|Full Text »|PDF »
NF{kappa}B activation is associated with its O-GlcNAcylation state under hyperglycemic conditions.
W. H. Yang, S. Y. Park, H. W. Nam, D. H. Kim, J. G. Kang, E. S. Kang, Y. S. Kim, H. C. Lee, K. S. Kim, and J. W. Cho (2008)
PNAS
105, 17345-17350
|Abstract »|Full Text »|PDF »
Identification of Structural and Functional O-Linked N-Acetylglucosamine-bearing Proteins in Xenopus laevis Oocyte.
V. Dehennaut, M.-C. Slomianny, A. Page, A.-S. Vercoutter-Edouart, C. Jessus, J.-C. Michalski, J.-P. Vilain, J.-F. Bodart, and T. Lefebvre (2008)
Mol. Cell. Proteomics
7, 2229-2245
|Abstract »|Full Text »|PDF »
O-GlcNAc Regulates FoxO Activation in Response to Glucose.
M. P. Housley, J. T. Rodgers, N. D. Udeshi, T. J. Kelly, J. Shabanowitz, D. F. Hunt, P. Puigserver, and G. W. Hart (2008)
J. Biol. Chem.
283, 16283-16292
|Abstract »|Full Text »|PDF »
An Extracellular Glycoprotein Is Implicated in Cell-Cell Contacts in the Toxic Cyanobacterium Microcystis aeruginosa PCC 7806.
Y. Zilliges, J.-C. Kehr, S. Mikkat, C. Bouchier, N. T. de Marsac, T. Borner, and E. Dittmann (2008)
J. Bacteriol.
190, 2871-2879
|Abstract »|Full Text »|PDF »
Protein Modification by O-Linked GlcNAc Reduces Angiogenesis by Inhibiting Akt Activity in Endothelial Cells.
B. Luo, Y. Soesanto, and D. A. McClain (2008)
Arterioscler Thromb Vasc Biol
28, 651-657
|Abstract »|Full Text »|PDF »
Functional Analysis of SPINDLY in Gibberellin Signaling in Arabidopsis.
A. L. Silverstone, T.-S. Tseng, S. M. Swain, A. Dill, S. Y. Jeong, N. E. Olszewski, and T.-p. Sun (2007)
Plant Physiology
143, 987-1000
|Abstract »|Full Text »|PDF »
Role of protein O-linked N-acetyl-glucosamine in mediating cell function and survival in the cardiovascular system.
N. Fulop, R. B. Marchase, and J. C. Chatham (2007)
Cardiovasc Res
73, 288-297
|Abstract »|Full Text »|PDF »
delayed flowering1 Encodes a Basic Leucine Zipper Protein That Mediates Floral Inductive Signals at the Shoot Apex in Maize.
M. G. Muszynski, T. Dam, B. Li, D. M. Shirbroun, Z. Hou, E. Bruggemann, R. Archibald, E. V. Ananiev, and O. N. Danilevskaya (2006)
Plant Physiology
142, 1523-1536
|Abstract »|Full Text »|PDF »
Role of Insulin, Adipocyte Hormones, and Nutrient-Sensing Pathways in Regulating Fuel Metabolism and Energy Homeostasis: A Nutritional Perspective of Diabetes, Obesity, and Cancer.
