| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
J Biol Chem, Vol. 273, Issue 6, 3611-3617, February 6, 1998
From the Department of Biochemistry and Cell Biology, Institute for
Cell and Developmental Biology, State University of New York,
Stony Brook, New York 11794-5215
O-Linked
N-acetylglucosamine (O-GlcNAc) is a ubiquitous
and abundant post-translational modification found on nuclear and cytoplasmic proteins and is thought to be a dynamically regulated modification much like phosphorylation. In this study we have demonstrated that
O-(2-acetamido-2-deoxy-D-glucopyranosylidene)amino-N-phenylcarbamate (PUGNAc), a potent in vitro inhibitor of the enzyme
responsible for the removal of O-GlcNAc from proteins
(peptide O-GlcNAc-
Modulation of O-Linked
N-Acetylglucosamine Levels on Nuclear and Cytoplasmic
Proteins in Vivo Using the Peptide
O-GlcNAc-
-N-acetylglucosaminidase Inhibitor
O-(2-Acetamido-2-deoxy-Dglucopyranosylidene)amino-N-phenylcarbamate
-N-acetylglucosaminidase), can be used to increase O-GlcNAc levels on nuclear and
cytoplasmic proteins in vivo. Overall, PUGNAc caused
approximately a 2-fold increase in O-GlcNAc levels in the
human colon cancer cells, HT29, although the effects on individual
proteins varied. The increase appeared to be the result of the direct
inhibition of the peptide O-GlcNAc--N-acetylglucosaminidase since
neither the O-GlcNAc transferase nor UDP-GlcNAc levels were
affected by the treatment. O-GlcNAc levels in other cell
lines tested (NIH 3T3, CV-1, and HeLa) were also affected by PUGNAc,
although the effects on HeLa cells were minimal. At the concentrations
tested, PUGNAc was non-toxic and had no affect on the growth rate of
any of the cell lines examined. Interestingly, we demonstrated that an
increase in O-GlcNAc levels on the transcription factor Sp1
resulted in a reciprocal decrease in its level of phosphorylation,
supporting the hypothesis that O-GlcNAc competes with
phosphate on some proteins. These studies demonstrate that PUGNAc is an
effective inhibitor of O-GlcNAc turnover within cells and
can be used to selectively alter the extent of O-GlcNAc on
cellular proteins.
Copyright © 1998 by The American Society for Biochemistry and Molecular Biology, Inc.
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  G. A. Ngoh and S. P. Jones New Insights into Metabolic Signaling and Cell Survival: The Role of {beta}-O-Linkage of N-Acetylglucosamine J. Pharmacol. Exp. Ther., December 1, 2008; 327(3): 602 - 609. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 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 NF{kappa}B activation is associated with its O-GlcNAcylation state under hyperglycemic conditions PNAS, November 11, 2008; 105(45): 17345 - 17350. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Y. Jiang, B. A. Woda, B. F. Banner, G. F. Whalen, K. A. Dresser, and D. Lu Sp1, a New Biomarker That Identifies a Subset of Aggressive Pancreatic Ductal Adenocarcinoma Cancer Epidemiol. Biomarkers Prev., July 1, 2008; 17(7): 1648 - 1652. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. J. Copeland, J. W. Bullen, and G. W. Hart Cross-talk between GlcNAcylation and phosphorylation: roles in insulin resistance and glucose toxicity Am J Physiol Endocrinol Metab, July 1, 2008; 295(1): E17 - E28. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Luo, Y. Soesanto, and D. A. McClain Protein Modification by O-Linked GlcNAc Reduces Angiogenesis by Inhibiting Akt Activity in Endothelial Cells Arterioscler. Thromb. Vasc. Biol., April 1, 2008; 28(4): 651 - 657. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Deng, B. Li, F. Liu, K. Iqbal, I. Grundke-Iqbal, R. Brandt, and C.-X. Gong Regulation between O-GlcNAcylation and phosphorylation of neurofilament-M and their dysregulation in Alzheimer disease FASEB J, January 1, 2008; 22(1): 138 - 145. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Rengifo, C. J. Gibson, E. Winkler, T. Collin, and B. E. Ehrlich Regulation of the Inositol 1,4,5-Trisphosphate Receptor Type I by O-GlcNAc Glycosylation J. Neurosci., December 12, 2007; 27(50): 13813 - 13821. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. A. Stubbs, M. Balcewich, B. L. Mark, and D. J. Vocadlo Small Molecule Inhibitors of a Glycoside Hydrolase Attenuate Inducible AmpC-mediated beta-Lactam Resistance J. Biol. Chem., July 20, 2007; 282(29): 21382 - 21391. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. Dehennaut, T. Lefebvre, C. Sellier, Y. Leroy, B. Gross, S. Walker, R. Cacan, J.-C. Michalski, J.-P. Vilain, and J.-F. Bodart O-Linked N-Acetylglucosaminyltransferase Inhibition Prevents G2/M Transition in Xenopus laevis Oocytes J. Biol. Chem., April 27, 2007; 282(17): 12527 - 12536. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Akimoto, G. W. Hart, L. Wells, K. Vosseller, K. Yamamoto, E. Munetomo, M. Ohara-Imaizumi, C. Nishiwaki, S. Nagamatsu, H. Hirano, et al. Elevation of the post-translational modification of proteins by O-linked N-acetylglucosamine leads to deterioration of the glucose-stimulated insulin secretion in the pancreas of diabetic Goto-Kakizaki rats Glycobiology, February 1, 2007; 17(2): 127 - 140. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Vosseller, J. C. Trinidad, R. J. Chalkley, C. G. Specht, A. Thalhammer, A. J. Lynn, J. O. Snedecor, S. Guan, K. F. Medzihradszky, D. A. Maltby, et al. O-Linked N-Acetylglucosamine Proteomics of Postsynaptic Density Preparations Using Lectin Weak Affinity Chromatography and Mass Spectrometry Mol. Cell. Proteomics, May 1, 2006; 5(5): 923 - 934. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Majumdar, A. Harrington, J. Hungerford, A. Martinez-Hernandez, I. C. Gerling, R. Raghow, and S. Solomon Insulin Dynamically Regulates Calmodulin Gene Expression by Sequential O-Glycosylation and Phosphorylation of Sp1 and Its Subcellular Compartmentalization in Liver Cells J. Biol. Chem., February 10, 2006; 281(6): 3642 - 3650. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. E. Ball, M. N. Berkaw, and M. G. Buse Identification of the Major Site of O-Linked {beta}-N-Acetylglucosamine Modification in the C Terminus of Insulin Receptor Substrate-1 Mol. Cell. Proteomics, February 1, 2006; 5(2): 313 - 323. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. G. Buse Hexosamines, insulin resistance, and the complications of diabetes: current status Am J Physiol Endocrinol Metab, January 1, 2006; 290(1): E1 - E8. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. H. Werstuck, M. I. Khan, G. Femia, A. J. Kim, V. Tedesco, B. Trigatti, and Y. Shi Glucosamine-Induced Endoplasmic Reticulum Dysfunction Is Associated With Accelerated Atherosclerosis in a Hyperglycemic Mouse Model Diabetes, January 1, 2006; 55(1): 93 - 101. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. J. Goldberg, C. I. Whiteside, G. W. Hart, and I. G. Fantus Posttranslational, Reversible O-Glycosylation Is Stimulated by High Glucose and Mediates Plasminogen Activator Inhibitor-1 Gene Expression and Sp1 Transcriptional Activity in Glomerular Mesangial Cells Endocrinology, January 1, 2006; 147(1): 222 - 231. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Nagy, V. Champattanachai, R. B. Marchase, and J. C. Chatham Glucosamine inhibits angiotensin II-induced cytoplasmic Ca2+ elevation in neonatal cardiomyocytes via protein-associated O-linked N-acetylglucosamine Am J Physiol Cell Physiol, January 1, 2006; 290(1): C57 - C65. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Slawson, N. E. Zachara, K. Vosseller, W. D. Cheung, M. D. Lane, and G. W. Hart Perturbations in O-linked {beta}-N-Acetylglucosamine Protein Modification Cause Severe Defects in Mitotic Progression and Cytokinesis J. Biol. Chem., September 23, 2005; 280(38): 32944 - 32956. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Ludemann, A. Clement, V. H. Hans, J. Leschik, C. Behl, and R. Brandt O-Glycosylation of the Tail Domain of Neurofilament Protein M in Human Neurons and in Spinal Cord Tissue of a Rat Model of Amyotrophic Lateral Sclerosis (ALS) J. Biol. Chem., September 9, 2005; 280(36): 31648 - 31658. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. S. Macauley, G. E. Whitworth, A. W. Debowski, D. Chin, and D. J. Vocadlo O-GlcNAcase Uses Substrate-assisted Catalysis: KINETIC ANALYSIS AND DEVELOPMENT OF HIGHLY SELECTIVE MECHANISM-INSPIRED INHIBITORS J. Biol. Chem., July 8, 2005; 280(27): 25313 - 25322. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z. T. Kneass and R. B. Marchase Protein O-GlcNAc Modulates Motility-associated Signaling Intermediates in Neutrophils J. Biol. Chem., April 15, 2005; 280(15): 14579 - 14585. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Majumdar, J. Wright, P. Markowitz, A. Martinez-Hernandez, R. Raghow, and S. S. Solomon Insulin Stimulates and Diabetes Inhibits O-Linked N-Acetylglucosamine Transferase and O-Glycosylation of Sp1 Diabetes, December 1, 2004; 53(12): 3184 - 3192. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z. T. Kneass and R. B. Marchase Neutrophils Exhibit Rapid Agonist-induced Increases in Protein-associated O-GlcNAc J. Biol. Chem., October 29, 2004; 279(44): 45759 - 45765. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Wells, L. K. Kreppel, F. I. Comer, B. E. Wadzinski, and G. W. Hart O-GlcNAc Transferase Is in a Functional Complex with Protein Phosphatase 1 Catalytic Subunits J. Biol. Chem., September 10, 2004; 279(37): 38466 - 38470. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Liu, K. Iqbal, I. Grundke-Iqbal, G. W. Hart, and C.-X. Gong O-GlcNAcylation regulates phosphorylation of tau: A mechanism involved in Alzheimer's disease PNAS, July 20, 2004; 101(29): 10804 - 10809. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. E. Zachara, N. O'Donnell, W. D. Cheung, J. J. Mercer, J. D. Marth, and G. W. Hart Dynamic O-GlcNAc Modification of Nucleocytoplasmic Proteins in Response to Stress: A SURVIVAL RESPONSE OF MAMMALIAN CELLS J. Biol. Chem., July 16, 2004; 279(29): 30133 - 30142. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. B. Arias, J. Kim, and G. D. Cartee Prolonged Incubation in PUGNAc Results in Increased Protein O-Linked Glycosylation and Insulin Resistance in Rat Skeletal Muscle Diabetes, April 1, 2004; 53(4): 921 - 930. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. O'Donnell, N. E. Zachara, G. W. Hart, and J. D. Marth Ogt-Dependent X-Chromosome-Linked Protein Glycosylation Is a Requisite Modification in Somatic Cell Function and Embryo Viability Mol. Cell. Biol., February 15, 2004; 24(4): 1680 - 1690. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Gewinner, G. Hart, N. Zachara, R. Cole, C. Beisenherz-Huss, and B. Groner The Coactivator of Transcription CREB-binding Protein Interacts Preferentially with the Glycosylated Form of Stat5 J. Biol. Chem., January 30, 2004; 279(5): 3563 - 3572. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. T. Kang, J. W. Ju, J. W. Cho, and E. S. Hwang Down-regulation of Sp1 Activity through Modulation of O-Glycosylation by Treatment with a Low Glucose Mimetic, 2-Deoxyglucose J. Biol. Chem., December 19, 2003; 278(51): 51223 - 51231. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. A. Whelan and G. W. Hart Proteomic Approaches to Analyze the Dynamic Relationships Between Nucleocytoplasmic Protein Glycosylation and Phosphorylation Circ. Res., November 28, 2003; 93(11): 1047 - 1058. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. J. Vocadlo, H. C. Hang, E.-J. Kim, J. A. Hanover, and C. R. Bertozzi A chemical approach for identifying O-GlcNAc-modified proteins in cells PNAS, August 5, 2003; 100(16): 9116 - 9121. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. L. E. Walgren, T. S. Vincent, K. L. Schey, and M. G. Buse High glucose and insulin promote O-GlcNAc modification of proteins, including alpha -tubulin Am J Physiol Endocrinol Metab, February 1, 2003; 284(2): E424 - E434. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Kamemura, B. K. Hayes, F. I. Comer, and G. W. Hart Dynamic Interplay between O-Glycosylation and O-Phosphorylation of Nucleocytoplasmic Proteins. ALTERNATIVE GLYCOSYLATION/PHOSPHORYLATION OF THR-58, A KNOWN MUTATIONAL HOT SPOT OF c-Myc IN LYMPHOMAS, IS REGULATED BY MITOGENS J. Biol. Chem., May 17, 2002; 277(21): 19229 - 19235. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Vosseller, L. Wells, M. D. Lane, and G. W. Hart Elevated nucleocytoplasmic glycosylation by O-GlcNAc results in insulin resistance associated with defects in Akt activation in 3T3-L1 adipocytes PNAS, April 16, 2002; 99(8): 5313 - 5318. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. A. HANOVER Glycan-dependent signaling: O-linked N-acetylglucosamine FASEB J, September 1, 2001; 15(11): 1865 - 1876. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X. Yang, K. Su, M. D. Roos, Q. Chang, A. J. Paterson, and J. E. Kudlow O-linkage of N-acetylglucosamine to Sp1 activation domain inhibits its transcriptional capability PNAS, May 18, 2001; (2001) 111099998. [Abstract] [Full Text]
|
|
|
|
|
|
X.-L. Du, D. Edelstein, L. Rossetti, I. G. Fantus, H. Goldberg, F. Ziyadeh, J. Wu, and M. Brownlee Hyperglycemia-induced mitochondrial superoxide overproduction activates the hexosamine pathway and induces plasminogen activator inhibitor-1 expression by increasing Sp1 glycosylation PNAS, October 24, 2000; 97(22): 12222 - 12226. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. J. Moloney, L. H. Shair, F. M. Lu, J. Xia, R. Locke, K. L. Matta, and R. S. Haltiwanger Mammalian Notch1 Is Modified with Two Unusual Forms of O-Linked Glycosylation Found on Epidermal Growth Factor-like Modules J. Biol. Chem., March 24, 2000; 275(13): 9604 - 9611. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Q. Chang, K. Su, J. R. Baker, X. Yang, A. J. Paterson, and J. E. Kudlow Phosphorylation of Human Glutamine:Fructose-6-phosphate Amidotransferase by cAMP-dependent Protein Kinase at Serine 205 Blocks the Enzyme Activity J. Biol. Chem., July 14, 2000; 275(29): 21981 - 21987. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Kaneto, G. Xu, K.-H. Song, K. Suzuma, S. Bonner-Weir, A. Sharma, and G. C. Weir Activation of the Hexosamine Pathway Leads to Deterioration of Pancreatic beta -Cell Function through the Induction of Oxidative Stress J. Biol. Chem., August 10, 2001; 276(33): 31099 - 31104. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Wells, Y. Gao, J. A. Mahoney, K. Vosseller, C. Chen, A. Rosen, and G. W. Hart Dynamic O-Glycosylation of Nuclear and Cytosolic Proteins. FURTHER CHARACTERIZATION OF THE NUCLEOCYTOPLASMIC beta -N-ACETYLGLUCOSAMINIDASE, O-GlcNAcase J. Biol. Chem., January 11, 2002; 277(3): 1755 - 1761. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. I. Comer and G. W. Hart O-Glycosylation of Nuclear and Cytosolic Proteins. DYNAMIC INTERPLAY BETWEEN O-GlcNAc AND O-PHOSPHATE J. Biol. Chem., September 15, 2000; 275(38): 29179 - 29182. [Full Text] [PDF]
|
|
|
|
|
|
X. Yang, K. Su, M. D. Roos, Q. Chang, A. J. Paterson, and J. E. Kudlow O-linkage of N-acetylglucosamine to Sp1 activation domain inhibits its transcriptional capability PNAS, June 5, 2001; 98(12): 6611 - 6616. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| All ASBMB Journals | Molecular and Cellular Proteomics |
| Journal of Lipid Research | ASBMB Today |
