Chemical tools to explore nutrient-driven O-GlcNAc cycling

Critical Reviews in Biochemistry and Molecular Biology

Volumn 49, Issue 4, 2014, Pages 327-342

  Kim, Eun J ^a   Bond, Michelle R ^b   Love, Dona C ^b   Hanover, John A ^b  

^a Daegu University   (South Korea)

^b NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES   (United States)

Author keywords

O GlcNAc; O GlcNAc transferase; OGT's activity assays; OGT's catalytic mechanism; OGT's inhibitors

Indexed keywords

ALLOXAN; CARBAMIC ACID DERIVATIVE; ENZYME INHIBITOR; N ACETYLGLUCOSAMINE; N ACETYLGLUCOSAMINE TRANSFERASE; PROTEINASE; PYROPHOSPHATE; SERINE; THREONINE; UNCLASSIFIED DRUG; URIDINE DIPHOSPHATE; URIDINE DIPHOSPHATE N ACETYLGLUCOSAMINE; ISOPROTEIN; N ACETYLGLUCOSAMINYLTRANSFERASE; UDP-N-ACETYLGLUCOSAMINE-PEPTIDE BETA-N-ACETYLGLUCOSAMINYLTRANSFERASE;

BINDING AFFINITY; CATALYSIS; ENZYME ACTIVITY; ENZYME LINKED IMMUNOSORBENT ASSAY; EXON; GENE STRUCTURE; HIGH THROUGHPUT SCREENING; HUMAN; INTRON; MOLECULAR BIOLOGY; NUTRIENT; PRIORITY JOURNAL; PROTEIN MODIFICATION; PROTEIN PROCESSING; REVIEW; TETRATRICOPEPTIDE REPEAT; ANALOGS AND DERIVATIVES; ANIMAL; ANTAGONISTS AND INHIBITORS; CHEMISTRY; ENZYME ASSAY; METABOLISM; PROCEDURES;

ACETYLGLUCOSAMINE; ANIMALS; ENZYME ASSAYS; ENZYME INHIBITORS; HUMANS; N-ACETYLGLUCOSAMINYLTRANSFERASES; PROTEIN ISOFORMS; PROTEIN PROCESSING, POST-TRANSLATIONAL;

EID: 84904698082     PISSN: 10409238     EISSN: 15497798     Source Type: Journal    
DOI: 10.3109/10409238.2014.931338     Document Type: Review

References (137)

1. Agard NJ, Bertozzi CR. (2009). Chemical approaches to perturb, profile, and perceive glycans. Acc Chem Res 42:788-97
2. Andrali SS, März P, Ö zcan S. (2005). Ataxin-10 interacts with OGlcNAc transferase OGT in pancreatic b cells. Biochem Biophys Res Commun 337:149-53
3. Beck M, Brickley K, Wilkinson HL, et al. (2002). Identification, molecular cloning, and characterization of a novel GABAA receptorassociated protein, GRIF-1. J Biol Chem 277:30079-90
4. Blatch GL, Lässle M. (1999). The tetratricopeptide repeat: A structural motif mediating protein-protein interactions. BioEssays 21:932-9
5. Blom N, Sicheritz-Pontén T, Gupta R, et al. (2004). Prediction of posttranslational glycosylation and phosphorylation of proteins from the amino acid sequence. Proteomics 4:1633-49
6. Borodkin VS, Schimpl M, Gundogdu M, et al. (2013). Bisubstrate UDPpeptide conjugates as human O-GlcNAc transferase inhibitors. Biochem J 457:497-502
7. Butkinaree C, Cheung WD, Park S, et al. (2008). Characterization of b-N-Acetylglucosaminidase cleavage by caspase-3 during cpoptosis. J Biol Chem 283:23557-66
8. Caldwell SA, Jackson SR, Shahriari KS, et al. (2010). Nutrient sensor OGlcNAc transferase regulates breast cancer tumorigenesis through targeting of the oncogenic transcription factor FoxM1. Oncogene 29: 2831-42
9. Cantarel BL, Coutinho PM, Rancurel C, et al. (2009). The carbohydrateactive enZymes database (CAZy): An expert resource for glycogenomics. Nucleic Acids Res 37:D233-8
10. Capotosti F, Guernier S, Lammers F, et al. (2011). O-GlcNAc Transferase catalyzes site-specific proteolysis of HCF-1. Cell 144: 376-88
11. Carrillo LD, Froemming JA, Mahal LK. (2011). Targeted in vivo OGlcNAc sensors reveal discrete compartment-specific dynamics during signal transduction. J Biol Chem 286:6650-8
12. Cetinbas N. Macauley MS. Stubbs KA. et al. 2006 Identification of Asp174 and Asp175 as the key catalytic residues of human OGlcNAcase by functional analysis of site-directed mutants. Biochemistry 45 3835-44
13. Champattanachai V, Marchase RB, Chatham JC. (2008). Glucosamine protects neonatal cardiomyocytes from ischemia-reperfusion injury via increased protein O-GlcNAc and increased mitochondrial Bcl-2. Am J Physiol Cell Physiol 294:C1509-20
14. Chatham JC, Marchase RB. (2010). Protein O-GlcNAcylation: A critical regulator of the cellular response to stress. Curr Signal Transduct Ther 5:49-59
15. Cheung WD, Hart GW. (2008). AMP-Activated protein kinase and p38 MAPK activate O-GlcNAcylation of neuronal proteins during glucose deprivation. J Biol Chem 283:13009-20
16. Cheung WD, Sakabe K, Housley MP, et al. (2008). O-Linked b-Nacetylglucosaminyltransferase substrate specificity is regulated by myosin phosphatase targeting and other interacting proteins. J Biol Chem 283:33935-41
17. Clarke AJ, Hurtado-Guerrero R, Pathak S, et al. (2008). Structural insights into mechanism and specificity of O-GlcNAc transferase. EMBO J 27:2780-8
18. Comer FI, Hart GW. (2001). Reciprocity between O-GlcNAc and O-phosphate on the carboxyl terminal domain of RNA Polymerase II. Biochemistry 40:7845-52
19. Conti E, Kuriyan J. (2000). Crystallographic analysis of the specific yet versatile recognition of distinct nuclear localization signals by karyopherin a. Structure 8:329-38
20. Conti E, Uy M, Leighton L, et al. (1998). Crystallographic analysis of the recognition of a nuclear localization signal by the nuclear import factor karyopherin a. Cell 94:193-204
21. D'Andrea LD, Regan L. (2003). TPR proteins: The versatile helix. Trends Biochem Sci 28:655-62
22. David LS, Tracey MG, Scott AY, David JV. (2012). Insights into O-linked N-Acetylglucosamine (O-GlcNAc) processing and dynamics through kinetic analysis of O-GlcNAc transferase and O-GlcNAcase activity on protein substrates. J Biol Chem 287:15395-408
23. Dehennaut V, Lefebvre, T, Sellier C, et al. (2007). O-Linked Nacetylglucosaminyltransferase inhibition prevents G2/M Transition in Xenopus laevis oocytes. J Biol Chem 282:12527-36
24. Dion HW, Fusari SA, Jakubowski ZL, et al. (1956). 6-Diazo-5-oxo- Lnorleucine, a new tumor-inhibitory substance. II. Isolation and characterization. J Am Chem Soc 78:3075-7
25. Dorfmueller HC, Borodkin VS, Blair DE, et al. (2011). Substrate and product analogues as human O-GlcNAc transferase inhibitors. Amino Acids 40:781-92
26. Du J, Meledeo MA, Wang Z, et al. (2009). Metabolic glycoengineering: Sialic acid and beyond. Glycobiology 19:1382-401
27. Du XL, Edelstein D, Dimmeler S, et al. (2001). Hyperglycemia inhibits endothelial nitric oxide synthase activity by posttranslational modification at the Akt site. J Clin Invest 108:1341-8
28. Fletcher BS, Draqstedt C, Notterpek L, Nolan GP. (2002). Functional cloning of SPIN-2, a nuclear anti-Apoptotic protein with roles in cell cycle progression. Leukemia 16:1507-18
29. Gao Y, Miyazaki J-I, Hart GW. (2003). The transcription factor PDX-1 is post-Translationally modified by O-linked N-Acetylglucosamine and this modification is correlated with its DNA binding activity and insulin secretion in min6 b-cells. Arch Biochem Biophys 415:155-63
30. Gao Y, Wells L, Comer FI, et al. (2001). Dynamic O-glycosylation of nuclear and cytosolic proteins: Cloning and characterization of a neutral, cytosolic b-N-Acetylglucosaminidase from human brain. J Biol Chem 276:9838-45
31. Gloster TM, Vocadlo DJ. (2010) Mechanism, structure, and inhibition of O-GlcNAc processing enzymes. Curr Signal Transduct Ther 5:74-91
32. Gloster TM, Zandberg WF, Heinonen JE, et al. (2011). Hijacking a biosynthetic pathway yields a glycosyltransferase inhibitor within cells. Nat Chem Biol 7:174-81
33. Gross BJ, Kraybill BC, Walker S. (2005). Discovery of O-GlcNAc transferase inhibitors. J Am Chem Soc 127:14588-9
34. Gross BJ, Swoboda JG, Walker S. (2008). A strategy to discover inhibitors of O-linked glycosylation. J Am Chem Soc 130:440-1
35. Hahne H, Sobotzki N, Nyberg T, et al. (2013). Proteome wide purification and identification of O-GlcNAc-modified proteins using click chemistry and mass spectrometry. J Proteome Res 12:927-36
36. Hajduch J, Nam G, Kim EJ, et al. (2008). A convenient synthesis of the C-1-phosphonate analogue of UDP-GlcNAc and its evaluation as an inhibitor of O-linked GlcNAc transferase (OGT). Carbohydr Res 343: 189-95
37. Haltiwanger RS, Blomberg MA, Hart GW. (1992). Glycosylation of nuclear and cytoplasmic proteins. Purification and characterization of a uridine diphospho-N-Acetylglucosamine: Polypeptide b-N-Acetylglucosaminyltransferase. J Biol Chem 267:9005-13
38. Haltiwanger RS, Holt GD, Hart GW. (1990). Enzymatic addition of O-GlcNAc to nuclear and cytoplasmic proteins. Identification of a uridine diphospho-N-Acetylglucosamine:peptide b-N-Acetylglucosaminyltransferase. J Biol Chem 265:2563-8
39. Hanover JA. (2001). Glycan-dependent signaling: O-linked N-Acetylglucosamine. FASEB J 15:1865-76
40. Hanover JA, Forsythe ME, Hennessey PT, et al. (2005). A Caenorhabditis elegans model of insulin resistance: Altered macronutrient storage and dauer formation in an OGT-1 knockout. Proc Natl Acad Sci USA 102:11266-71
41. Hanover JA, Yu S, Lubas WB, et al. (2003). Mitochondrial and nucleocytoplasmic isoforms of O-linked GlcNAc transferase encoded by a single mammalian gene. Arch Biochem Biophys 409:287-97
42. Hart GW, Housley MP, Slawson C. (2007). Cycling of O-linked b-Nacetylglucosamine on nucleocytoplasmic proteins. Nature 446: 1017-22
43. Hart GW, Slawson C, Ramirez-Correa G, Lagerlof O. (2011). Cross talk between O-GlcNAcylation and phosphorylation: Roles in signaling, transcription, and chronic disease. Annu Rev Biochem 80:825-58
44. He Y, Macauley MS, Stubbs KA, et al. (2010). Visualizing the reaction coordinate of an O-GlcNAc hydrolase. J Am Chem Soc 132:1807-9
45. Housley MP, Udeshi ND, Rodgers JT, et al. (2009). A PGC-1a-OGlcNAc transferase complex regulates FoxO transcription factor activity in response to glucose. J Biol Chem 284:5148-57
46. Huber AH, Weis WI. (2001). The structure of the b-catenin/E-cadherin complex and the molecular basis of diverse ligand recognition by b-catenin. Cell 105:391-402
47. Iyer SPN, Akimoto Y, Hart GW. (2003). Identification and cloning of a novel family of coiled-coil domain proteins that interact with O-GlcNAc transferase. J Biol Chem 278:5399-409
48. Iyer SPN, Hart GW. (2003). Roles of the tetratricopeptide repeat domain in O-GlcNAc transferase targeting and protein substrate specificity. J Biol Chem 278:24608-16
49. Izumi M, Yuasa H, Hashimoto H. (2009). Bisubstrate analogues as glycosyltransferase inhibitors. Curr Top Med Chem 9:87-105
50. Jancan I, Macnaughtan MA. (2012). Acid dissociation constants of uridine-50-diphosphate compounds determined by 31phosphorus nuclear magnetic resonance spectroscopy and internal pH referencing. Anal Chim Acta 749:63-9
51. Jia C, Liu T, Wang Z. (2013). O-GlcNAcPRED: A sensitive predictor to capture protein O-GlcNAcylation sites. Mol BioSyst 9:2909-13
52. Jiang J, Lazarus MB, Pasquina L, et al. (2012). A neutral diphosphate mimic crosslinks the active site of human O-GlcNAc transferase. Nat Chem Biol 8:72-7
53. Jinek M, Rehwinkel J, Lazarus BD, et al. (2004). The superhelical TPRrepeat domain of O-linked GlcNAc transferase exhibits structural similarities to importin a. Nat Struct Mol Biol 11:1001-7
54. Jones MB, Teng H, Rhee JK, et al. (2004). Characterization of the cellular uptake and metabolic conversion of acetylated N-Acetylmannosamine (ManNAc) analogues to sialic acids. Biotechnol Bioeng 85: 394-405
55. Kang E-S, Han D, Park J, et al. (2008). O-GlcNAc modulation at Akt1 Ser473 correlates with apoptosis of murine pancreatic b cells. Exp Cell Res 314:2238-48
56. Keppler OT, Horstkorte R, Pawlita M, et al. (2001). Biochemical engineering of the N-Acyl side chain of sialic acid: Biological implications. Glycobiology 11:11R-8R.
57. Kim EJ. (2011). Chemical arsenal for the study of O-GlcNAc. Molecules 16:1987-2022
58. Kim EJ, Hanover JA. (2013). Enzymatic characterization of recombinant enzymes of O-GlcNAc cycling. In: Brockhausen I, ed. Methods in molecular biology. Volume 1022: Glycosyltransferase: Methods and protocols. New York: Human Press, 129-45
59. Kim EJ, Abramowitz LK, Bond MR, et al. (2014). Versatile O-GlcNAc transferase assay for high-Throughput identification of enzyme variants, substrates, and inhibitors. Bioconjug Chem. DOI: 10.1021/bc5001774
60. Kim EJ, Kang DO, Love DC, Hanover JA. (2006a). Enzymatic characterization of O-GlcNAcase isoforms using a fluorogenic GlcNAc substrate. Carbohydr Res 341:971-82
61. Kim EJ, Perreira M, Thomas CJ, Hanover JA. (2006b). An O-GlcNAcase-specific inhibitor and substrate engineered by the extension of the N-Acetyl moiety. J Am Chem Soc 128:4234-5
62. Knight ZA, Shokat KM. (2007). Chemical genetics: Where genetics and pharmacology meet. Cell 128:425-30
63. Koivula A, Ruohonen L, Wohlfahrt G, et al. (2002). The active site of cellobiohydrolase Cel6A from Trichoderma reesei: The roles of aspartic acids D221 and D175. J Am Chem Soc 124:10015-24
64. Kolm-Litty V, Sauer U, Nerlich A, et al. (1998). High glucose-induced transforming growth factor b1 production is mediated by the hexosamine pathway in porcine glomerular mesangial cells. J Clin Invest 101:160-9
65. Konrad RJ, Zhang F, Hale JE, et al. (2002). Alloxan is an inhibitor of the enzyme O-linked N-Acetylglucosamine transferase. Biochem Biophys Res Commun 293:207-12
66. Kreppel LK, Blomberg MA, Hart GW. (1997). Dynamic glycosylation of nuclear and cytosolic proteins: Cloning and charaterization of a unique O-GlcNAc transferase with multiple tetratricopeptide repeats. J Biol Chem 272:9308-15
67. Kreppel LK, Hart GW. (1999). Regulation of a cytosolic and nuclear O-GlcNAc transferase: Role of the tetratricopeptide repeats. J Biol Chem 274:32015-22
68. Laczy B, Hill BG, Wang K, et al. (2009). Protein O-GlcNAcylation: A new signaling paradigm for the cardiovascular system. Am J Physiol Heart Circ Physiol 296:H13-28
69. Lavogina D, Enkvist E, Uri A. (2010). Bisubstrate inhibitors of protein kinases: From principle to practical applications. Chem Med Chem 5: 23-34
70. Lazarus BD, Love DC, Hanover JA. (2006). Recombinant O-GlcNAc transferase isoforms: Identification of O-GlcNAcase, yes tyrosine kinase, and tau as isoform-specific substrates. Glycobiology 16: 415-21
71. Lazarus BD, Love DC, Hanover JA. (2009). O-GlcNAc cycling: Implications for neurodegenerative disorders. Int J Biochem Cell Biol 41:2134-46
72. Lazarus MB, Jiang J, Gloster TM, et al. (2012). Structural snapshots of the reaction coordinate for O-GlcNAc transferase. Nat Chem Biol 8: 966-8
73. Lazarus MB, Nam Y, Jiang J, et al. (2011). Structure of human O-GlcNAc transferase and its complex with a peptide substrate. Nature 469:564-7
74. Leavy TM, Bertozzi CR. (2007). A high-Throughput assay for O-GlcNAc transferase detects primary sequence preferences in peptide substrates. Bioorg Med Chem Lett 17:3851-4
75. Lee TN, Alborn WE, Knierman MD, Konrad RJ. (2006). Alloxan is an inhibitor of O-GlcNAc-selective N-Acetyl-b-D-glucosaminidase. Biochem Biophys Res Commun 350:1038-43
76. Lenzen S, Munday R. (1991). Thiol-group reactivity, hydrophilicity and stability of alloxan, its reduction products and its N-methyl derivatives and a comparison with ninhydrin. Biochem Pharmacol 42:1385-91
77. Lenzen S, Panten U. (1988). Alloxan: History and mechanism of action. Diabetologia 31:337-42
78. Liu F, Iqbal K, Grundke-Iqbal I, et al. (2004). O-GlcNAcylation regulates phosphorylation of tau: A mechanism involved in Alzheimer's disease. Proc Natl Acad Sci USA 101:10804-9
79. Liu J, Marchase RB, Chatham JC. (2007). Glutamine-induced protection of isolated rat heart from ischemia/reperfusion injury is mediated via the hexosamine biosynthesis pathway and increased protein O-GlcNAc levels. J Mol Cell Cardiol 42:177-85
80. Liu J, Pang Y, Chang T, et al. (2006). Increased hexosamine biosynthesis and protein O-GlcNAc levels associated with myocardial protection against calcium paradox and ischemia. J Mol Cell Cardiol 40:303-12
81. Liu J, Yu Y, Fan YZ, et al. (2005). Cardiovascular effects of endomorphins in alloxan-induced diabetic rats. Peptides 26:607-14
82. Liu X, Li L, Wang Y, et al. (2014). A peptide panel investigation reveals the acceptor specifity of O-GlcNAc transferase. FASEB J [Online] Available from: Http://www.fasebj.org/content/early/2014/04/23/fj.13-246850.long [last accessed 23 April 2014].
83. Love DC, Hanover JA. (2005). The hexosamine signaling pathway: Deciphering the "O-GlcNAc Code." Sci STKE 2005, re13
84. Love DC, Kochran J, Cathey RL, et al. (2003). Mitochondrial and nucleocytoplasmic targeting of O-linked GlcNAc transferase. J Cell Sci 116:647-54
85. Lubas WA, Frank DW, Krause M, Hanover JA. (1997). O-Linked GlcNAc transferase is a conserved nucleocytoplasmic protein containing tetratricopeptide repeats. J Biol Chem 272:9316-24
86. Lubas WA, Hanover JA. (2000). Functional expression of O-linked GlcNAc transferase: Domain structure and substrate specificity. J Biol Chem 275:10983-8
87. Müller R, Jenny A, Stanley P. (2013). The EGF repeat-specific O-GlcNAc-Transferase Eogt interacts with notch signaling and pyrimidine metabolism pathways in Drosophila. PLoS ONE 8:e62835
88. Macauley MS, Vocadlo DJ. (2010). Increasing O-GlcNAc levels: An overview of small-molecule inhibitors of O-GlcNAcase. Biochim Biophys Acta 1800:107-21
89. Macauley MS, Whitworth GE, Debowski AW, et al. (2005). O-GlcNAcase uses substrate-Assisted catalysis: Kinetic analysis and development of highly selective mechanism-inspired inhibitors. J Biol Chem 280:25313-22
90. Majumdar G, Harmon A, Candelaria R, et al. (2003). O-glycosylation of Sp1 and transcriptional regulation of the calmodulin gene by insulin and glucagon. Am J Physiol Endocrinol Metab 285:E584-91
91. Marshall S, Bacote V, Traxinger RR. (1991). Discovery of a metabolic pathway mediating glucose-induced desensitization of the glucose transport system. Role of hexosamine biosynthesis in the induction of insulin resistance. J Biol Chem 266:4706-12
92. Martinez-Fleites C, Macauley MS, He Y, et al. (2008). Structure of an O-GlcNAc transferase homolog provides insight into intracellular glycosylation. Nat Struct Mol Biol 15:764-5
93. Mayer TU. (2003). Chemical genetics: Tailoring tools for cell biology. Trends Cell Biol 13:270-7
94. McClain DA, Lubas WA, Cooksey RC, et al. (2002). Altered glycandependent signaling induces insulin resistance and hyperleptinemia. Proc Natl Acad Sci USA 99:10695-9
95. Ngoh GA, Facundo HT, Zafir A, Jones SP. (2010). O-GlcNAc signaling in the cardiovascular system. Circ Res 107:171-85
96. Ngoh GA, Watson LJ, Facundo HT, et al. (2008). Non-canonical glycosyltransferase modulates post-hypoxic cardiac myocyte death and mitochondrial permeability transition. J Mol Cell Cardiol 45: 313-25
97. Noach N, Segev Y, Levi I, et al. (2007). Modification of topoisomerase I activity by glucose and by O-Glcnacylation of the enzyme protein. Glycobiology 17:1357-64
98. Nolte D, Müller U. (2002). Human O-GlcNAc transferase (OGT): Genomic structure, analysis of splice variants, fine mapping in Xq13.1. Mamm Genome 13:62-4
99. O'Donnell N, Zachara NE, Hart GW, Marth JD. (2004). Ogt-dependent X-chromosome-linked protein glycosylation is a requisite modification in somatic cell function and embryo viability. Mol Cell Biol 24: 1680-90
100. Offen W, Martinez-Fleites C, Yang M, et al. (2006). Structure of a flavonoid glucosyltransferase reveals the basis for plant natural product modification. EMBO J 25:1396-405
101. Olszewski NE, West CM, Sassi SO, Hartweck LM. (2010). O-GlcNAc protein modification in plants: Evolution and function. Biochim Biophys Acta 1800:49-56
102. Ostrowski A, van Aalten DMF. (2013). Chemical tools to probe cellular O-GlcNAc signalling. Biochem J 456:1-12
103. Palcic MM, Heerze LD, Srivastava OP, Hindsgaul O. (1989). A bisubstrate analog inhibitor for alpha (1-2)-fucosyltransferase. J Biol Chem 264:17174-81
104. Rao FV, Schüttelkopf AW, Dorfmueller HC, et al. (2013). Structure of a bacterial putative acetyltransferase defines the fold of the human O-GlcNAcase C-Terminal domain. Open Biol 3:130021
105. Rex-Mathes M, Werner S, Strutas D, et al. (2001). O-GlcNAc expression in Developing and ageing mouse brain. Biochimie 83:583-90
106. Ryu IH, Do SI. (2011). Denitrosylation of S-nitrosylated OGT is triggered in LPS-stimulated innate immune response. Biochem Biophys Res Commun 408:52-7
107. Sakaidani Y, Ichiyanagi N, Saito C, et al. (2012). O-linked- Nacetylglucosamine modification of mammalian Notch receptors by an atypical O-GlcNAc transferase Eogt1. Biochem Biophys Res Commun 419:14-19
108. Schimpl M, Zheng X, Borodkin VS, et al. (2012). O-GlcNAc transferase invokes nucleotide sugar pyrophosphate participation in catalysis. Nat Chem Biol 8:969-74
109. Shafi R, Iyer SPN, Ellies LG, et al. (2000). The O-GlcNAc transferase gene resides on the X chromosome and is essential for embryonic stem cell viability and mouse ontogeny. Proc Natl Acad Sci USA 97: 5735-9
110. Shaheen R, Aglan M, Keppler-Noreuil K, et al. (2013). Mutations in EOGT confirm the genetic heterogeneity of autosomal-recessive Adams-Oliver Syndrome. Am J Hum Genet 92:598-604
111. Sinclair DAR, Syrzycka M, Macauley MS, et al. (2009). Drosophila O-GlcNAc transferase (OGT) is encoded by the Polycomb group (PcG) gene, super sex combs (sxc). Proc Natl Acad Sci USA 106: 13427-32
112. Slawson C, Zachara NE, Vosseller K, et al. (2005). Perturbations in O-linked b-N-Acetylglucosamine protein modification cause severe defects in mitotic progression and cytokinesis. J Biol Chem 280: 32944-56
113. Song M, Kim HS, Park JM, et al. (2008). O-GlcNAc transferase is activated by CaMKIV-dependent phosphorylation under potassium chloride-induced depolarization in NG-108-15 cells. Cell Signal 20: 94-104
114. Staiano N, Everson RB, Cooney DA, et al. (1980). Mutagenicity of dand l-Azaserine, 6-diazo-5-oxo-l-norleucine and N-(N-methyl-Nnitroso-carbamyl)-l- ornithine in the Salmonella test system. Mutat Res 79:387-90
115. Thornton TM, Swain SM, Olszewski NE. (1999). Gibberellin signal transduction presents ellipsisthe SPY who O-GlcNAc'd me. Trends Plant Sci 4:424-8
116. Toleman C, Paterson AJ, Whisenhunt TR, Kudlow JE. (2004). Characterization of the histone acetyltransferase (HAT) domain of a bifunctional protein with activable O-GlcNAcase and HAT activities. J Biol Chem 279:53665-73
117. Tsuruta O, Shinohara G, Yuasa H, Hashimoto H. (1997). UDP-N-Acetyl-5-Thio-galactosamine is a substrate of lactose synthase. Bioorg Med Chem Lett 7:2523-6
118. Tsuruta O, Yuasa H, Hashimoto H, et al. (2003). Synthesis of GDP-5-Thiosugars and their use as glycosyl donor substrates for glycosyltransferases. J Org Chem 68:6400-6
119. Tvaroška I, Kozmon S, Wimmerová M, Koča J. (2012). Substrateassisted catalytic mechanism of O-GlcNAc transferase discovered by quantum mechanics/molecular mechanics investigation. J Am Chem Soc 134:15563-71
120. Vocadlo DJ, Hang HC, Kim EJ, et al. (2003). A chemical approach for identifying O-GlcNAc-modified proteins in cells. Proc Natl Acad Sci USA 100:9116-21
121. Vosseller K, Wells L, Lane MD, Hart GW. (2002). Elevated nucleocytoplasmic glycosylation by O-GlcNAc results in insulin resistance associated with defects in Akt activation in 3T3-L1 adipocytes. Proc Natl Acad Sci USA 99:5313-18
122. Wang J, Torii M, Liu H, et al. (2011) dbOGAP-An integrated bioinformatics resource for protein O-GlcNAcylation. BMC Bioinforma 12:91
123. Wells L, Kreppel LK, Comer FI, et al. (2004). O-GlcNAc transferase is in a functional complex with protein phosphatase 1 catalytic subunits. J Biol Chem 279:38466-70
124. Wells L, Vosseller K, Hart GW. (2001). Glycosylation of nucleocytoplasmic proteins: Signal transduction and O-GlcNAc. Science 291: 2376-8
125. Whelan SA, Lane MD, Hart GW. (2008). Regulation of the O-Linked b-N-Acetylglucosamine transferase by insulin signaling. J Biol Chem 283:21411-17
126. Whisenhunt TR, Yang X, Bowe DB, et al. (2006). Disrupting the enzyme complex regulating O-GlcNAcylation blocks signaling and development. Glycobiology 16:551-63
127. Withers SG, Davies GJ. (2012). The case of the missing base. Nat Chem Biol 8:952-3
128. Wrabl JO, Grishin NV. (2001). Homology between O-linked GlcNAc transferases and proteins of the glycogen phosphorylase superfamily. J Mol Biol 314:365-74
129. Wu F, Lukinius A, BergströmM, et al. (1999). A mechanism behind the antitumour effect of 6-diazo-5-oxo-l-norleucine (DON): Disruption of mitochondria. Eur J Cancer 35:1155-61
130. Xing D, Feng W, Nöt LG, et al. (2008). Increased protein O-GlcNAc modification inhibits inflammatory and neointimal responses to acute endoluminal arterial injury. Am J Physiol Heart Circ Physiol 295: H335-42
131. Yang X, Ongusaha PP, Miles PD, et al. (2008). Phosphoinositide signalling links O-GlcNAc transferase to insulin resistance. Nature 451:964-9
132. Yang X, Zhang F, Kudlow JE. (2002). Recruitment of O-GlcNAc transferase to promoters by corepressor mSin3A: Coupling protein O-GlcNAcylation to transcriptional repression. Cell 110:69-80
133. Yuzwa SA, Macauley MS, Heinonen JE, et al. (2008). A potent mechanism-inspired O-GlcNAcase inhibitor that blocks phosphorylation of tau in vivo. Nat Chem Biol 4:483-90
134. Zachara NE, O'Donnell N, Cheung WD, et al. (2004). Dynamic O-GlcNAc modification of nucleocytoplasmic proteins in response to stress: A survival response of mamalian cells. J Biol Chem 279: 30133-42
135. Zhang F, Hu Y, Huang P, et al. (2007). Proteasome function is regulated by cyclic AMP-dependent protein kinase through phosphorylation of Rpt6. J Biol Chem 282:22460-71
136. Zhang F, Su K, Yang X, et al. (2003). O-GlcNAc modification is an endogenous inhibitor of the proteasome. Cell 115:715-25
137. Zhang H, Gao G, Brunk UT. (1992). Extracellular reduction of alloxan results in oxygen radical-mediated attack on plasma and lysosomal membranes. APMIS 100:317-25 Kidney Diseases