Bittersweet memories: Linking metabolism to epigenetics through O-GlcNAcylation

Nature Reviews Molecular Cell Biology

Volumn 13, Issue 5, 2012, Pages 312-321

  Hanover, John A ^a   Krause, Michael W ^a   Love, Dona C ^a  

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

Author keywords

[No Author keywords available]

Indexed keywords

ENDOTHELIAL NITRIC OXIDE SYNTHASE; GLYCOSYLTRANSFERASE; HISTONE; HISTONE DEACETYLASE; HISTONE DEACETYLASE 1; N ACETYLGLUCOSAMINE; OCTAMER TRANSCRIPTION FACTOR 4; POLYCOMB GROUP PROTEIN; RNA POLYMERASE II; TAU PROTEIN; TRANSFERASE;

ALZHEIMER DISEASE; CARBOXY TERMINAL SEQUENCE; CELL FUNCTION; CRYSTAL STRUCTURE; DEGENERATIVE DISEASE; DIABETES MELLITUS; EMBRYO DEVELOPMENT; EPIGENETICS; GENE EXPRESSION; GENE REPRESSION; GENETIC ANALYSIS; GENOME IMPRINTING; GLUCONEOGENESIS; HISTONE MODIFICATION; HOMEOSTASIS; HUMAN; INSULIN RESISTANCE; INTRACELLULAR SIGNALING; MASS SPECTROMETRY; NONHUMAN; NUTRIENT AVAILABILITY; OBESITY; PRIORITY JOURNAL; PROTEIN BINDING; PROTEIN FUNCTION; PROTEIN GLYCOSYLATION; PROTEIN MOTIF; PROTEIN PROCESSING; PROTEIN STRUCTURE; REVIEW; RNA INTERFERENCE; TRANSCRIPTION INITIATION; TRANSCRIPTION REGULATION; X CHROMOSOME INACTIVATION;

ACETYLGLUCOSAMINE; ACETYLGLUCOSAMINIDASE; ANIMALS; CHROMATIN; EPIGENESIS, GENETIC; GLYCOSYLATION; HUMANS; METABOLIC NETWORKS AND PATHWAYS; N-ACETYLGALACTOSAMINYLTRANSFERASES; NUTRITIONAL STATUS; PROTEIN CONFORMATION; PROTEIN PROCESSING, POST-TRANSLATIONAL;

EID: 84860184939     PISSN: 14710072     EISSN: 14710080     Source Type: Journal    
DOI: 10.1038/nrm3334     Document Type: Review

References (112)

1. Young, N. L., Dimaggio, P. A. & Garcia, B. A. The significance, development and progress of high-throughput combinatorial histone code analysis. Cell. Mol. Life Sci. 67, 3983-4000 (2010).
2. Hanover, J. A. Epigenetics gets sweeter: O-GlcNAc joins the "histone code". Chem. Biol. 17, 1272-1274 (2010).
3. Spiro, R. G. Protein glycosylation: nature, distribution, enzymatic formation, and disease implications of glycopeptide bonds. Glycobiology 12, 43R-56R (2002). (Pubitemid 34760066)
4. Davies, G. J., Gloster, T. M. & Henrissat, B. Recent structural insights into the expanding world of carbohydrate-active enzymes. Curr. Opin. Struct. Biol. 15, 637-645 (2005). (Pubitemid 41668519)
5. Muegge, B. D. et al. Diet drives convergence in gut microbiome functions across mammalian phylogeny and within humans. Science 332, 970-974 (2011).
6. Gambetta, M. C., Oktaba, K. & Muller, J. Essential role of the glycosyltransferase sxc/Ogt in polycomb repression. Science 325, 93-96 (2009).
7. Sinclair, D. A. et al. Drosophila O-GlcNAc transferase (OGT) is encoded by the Polycomb group (PcG) gene, super sex combs (sxc). Proc. Natl Acad. Sci. USA 106, 13427-13432 (2009).
8. Love, D. C. et al. Dynamic O-GlcNAc cycling at promoters of Caenorhabditis elegans genes regulating longevity, stress, and immunity. Proc. Natl Acad. Sci. USA 107, 7413-7418 (2010).
9. Hanover, J. A. & Lennarz, W. J. Transmembrane assembly of membrane and secretory glycoproteins. Arch. Biochem. Biophys. 211, 1-19 (1981).
10. Hanover, J. A. & Lennarz, W. J. Transmembrane assembly of N-linked glycoproteins. Studies on the topology of saccharide synthesis. J. Biol. Chem. 257, 2787-2794 (1982).
11. Burda, P. & Aebi, M. The dolichol pathway of N-linked glycosylation. Biochim. Biophys. Acta 1426, 239-257 (1999). (Pubitemid 29027942)
12. Helenius, J. & Aebi, M. Transmembrane movement of dolichol linked carbohydrates during N-glycoprotein biosynthesis in the endoplasmic reticulum. Semin. Cell Dev. Biol. 13, 171-178 (2002). (Pubitemid 35304520)
13. Liu, L., Xu, Y. X. & Hirschberg, C. B. The role of nucleotide sugar transporters in development of eukaryotes. Semin. Cell Dev. Biol. 21, 600-608 (2010).
14. Holt, G. D. & Hart, G. W. The subcellular distribution of terminal N-acetylglucosamine moieties. Localization of a novel protein-saccharide linkage, O-linked GlcNAc. J. Biol. Chem. 261, 8049-8057 (1986). (Pubitemid 17208742)
15. Hanover, J. A., Cohen, C. K., Willingham, M. C. & Park, M. K. O-linked N-acetylglucosamine is attached to proteins of the nuclear pore. Evidence for cytoplasmic and nucleoplasmic glycoproteins. J. Biol. Chem. 262, 9887-9894 (1987).
16. Kamemura, K. & Hart, G. W. Dynamic interplay between O-glycosylation and O-phosphorylation of nucleocytoplasmic proteins: a new paradigm for metabolic control of signal transduction and transcription. Prog. Nucleic Acid Res. Mol. Biol. 73, 107-136 (2003). (Pubitemid 137639541)
17. Capotosti, F. et al. O-GlcNAc transferase catalyzes site-specific proteolysis of HCF1. Cell 144, 376-388 (2011).
18. Daou, S. et al. Crosstalk between O-GlcNAcylation and proteolytic cleavage regulates the host cell factor1 maturation pathway. Proc. Natl Acad. Sci. USA 108, 2747-2752 (2011).
19. Sakabe, K., Wang, Z. & Hart, G. W. β-N-acetylglucosamine (O-GlcNAc) is part of the histone code. Proc. Natl Acad. Sci. USA 107, 19915-19920 (2010).
20. Zhang, S., Roche, K., Nasheuer, H. P. & Lowndes, N. F. Modification of histones by sugar β-N-acetylglucosamine (GlcNAc) occurs on multiple residues, including histone H3 serine 10, and is cell cycle-regulated. J. Biol. Chem. 286, 37483-37495 (2011).
21. Fujiki, R. et al. GlcNAcylation of histone H2B facilitates its monoubiquitination. Nature 480, 557-560 (2011).
22. Comer, F. I. & Hart, G. W. Reciprocity between O-GlcNAc and O-phosphate on the carboxyl terminal domain of RNA polymerase II. Biochemistry 40, 7845-7852 (2001). (Pubitemid 32622975)
23. Love, D. C., Krause, M. W. & Hanover, J. A. O-GlcNAc cycling: emerging roles in development and epigenetics. Semin. Cell Dev. Biol. 21, 646-654 (2010).
24. Love, D. C. & Hanover, J. A. The hexosamine signaling pathway: deciphering the "O-GlcNAc code". Sci. STKE 2005, re13 (2005).
25. Butkinaree, C., Park, K. & Hart, G. W. O-linked β-N- acetylglucosamine (O-GlcNAc): extensive crosstalk with phosphorylation to regulate signaling and transcription in response to nutrients and stress. Biochim. Biophys. Acta 1800, 96-106 (2010).
26. Traxinger, R. R. & Marshall, S. Coordinated regulation of glutamine:fructose-6-phosphate amidotransferase activity by insulin, glucose, and glutamine. Role of hexosamine biosynthesis in enzyme regulation. J. Biol. Chem. 266, 10148-10154 (1991). (Pubitemid 21906780)
27. Marshall, S., Bacote, V. & Traxinger, R. R. 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, 4706-4712 (1991). (Pubitemid 21909414)
28. Olszewski, N. E., West, C. M., Sassi, S. O. & Hartweck, L. M. O-GlcNAc protein modification in plants: evolution and function. Biochim. Biophys. Acta 1800, 49-56 (2010).
29. Lubas, W. A., Frank, D. W., Krause, M. & Hanover, J. A. O-Linked GlcNAc transferase is a conserved nucleocytoplasmic protein containing tetratricopeptide repeats. J. Biol. Chem. 272, 9316-9324 (1997). (Pubitemid 27154944)
30. Kreppel, L. K., Blomberg, M. A. & Hart, G. W. Dynamic glycosylation of nuclear and cytosolic proteins. Cloning and characterization of a unique O-GlcNAc transferase with multiple tetratricopeptide repeats. J. Biol. Chem. 272, 9308-9315 (1997). (Pubitemid 27154943)
31. Kreppel, L. K. & Hart, G. W. Regulation of a cytosolic and nuclear O-GlcNAc transferase. Role of the tetratricopeptide repeats. J. Biol. Chem. 274, 32015-32022 (1999).
32. Lubas, W. A. & Hanover, J. A. Functional expression of O-linked GlcNAc transferase. Domain structure and substrate specificity. J. Biol. Chem. 275, 10983-10988 (2000). (Pubitemid 30212736)
33. Hanover, J. A. et al. Mitochondrial and nucleocytoplasmic isoforms of O-linked GlcNAc transferase encoded by a single mammalian gene. Arch. Biochem. Biophys. 409, 287-297 (2003). (Pubitemid 36259596)
34. Love, D. C., Kochan, J., Cathey, R. L., Shin, S. H. & Hanover, J. A. Mitochondrial and nucleocytoplasmic targeting of O-linked GlcNAc transferase. J. Cell Sci. 116, 647-654 (2003). (Pubitemid 36231303)
35. Shin, S. H., Love, D. C. & Hanover, J. A. Elevated O-GlcNAcdependent signaling through inducible mOGT expression selectively triggers apoptosis. Amino Acids 40, 885-893 (2011).
36. Jinek, M. et al. The superhelical TPR-repeat domain of O-linked GlcNAc transferase exhibits structural similarities to importin-α. Nature Struct. Mol. Biol. 11, 1001-1007 (2004). (Pubitemid 39315305)
37. Lazarus, M. B., Nam, Y., Jiang, J., Sliz, P. & Walker, S. Structure of human O-GlcNAc transferase and its complex with a peptide substrate. Nature 469, 564-567 (2011).
38. Swinburne, I. A. & Silver, P. A. Intron delays and transcriptional timing during development. Dev. Cell 14, 324-330 (2008).
39. Ashton-Beaucage, D. et al. The exon junction complex controls the splicing of MAPK and other long intron-containing transcripts in Drosophila. Cell 143, 251-262 (2010).
40. Ryu, I. H. & Do, S. I. Denitrosylation of S-nitrosylated OGT is triggered in LPS-stimulated innate immune response. Biochem. Biophys. Res. Commun. 408, 52-57 (2011).
41. Gao, Y., Wells, L., Comer, F. I., Parker, G. J. & Hart, G. W. Dynamic O-glycosylation of nuclear and cytosolic proteins: cloning and characterization of a neutral, cytosolic β-N-acetylglucosaminidase from human brain. J. Biol. Chem. 276, 9838-9845 (2001).
42. Hanover, J. A., Krause, M. W. & Love, D. C. The hexosamine signaling pathway: O-GlcNAc cycling in feast or famine. Biochim. Biophys. Acta 1800, 80-95 (2010).
43. Keembiyehetty, C. N., Krzeslak, A., Love, D. C. & Hanover, J. A. A lipid-droplet-targeted O-GlcNAcase isoform is a key regulator of the proteasome. J. Cell Sci. 124, 2851-2860 (2011).
44. Gloster, T. M. & Vocadlo, D. J. Mechanism, structure, and inhibition of O-GlcNAc processing enzymes. Curr. Signal Transduct Ther. 5, 74-91 (2010).
45. Rao, F. V. et al. Structural insights into the mechanism and inhibition of eukaryotic O-GlcNAc hydrolysis. EMBO J. 25, 1569-1578 (2006).
46. Schimpl, M., Schuttelkopf, A. W., Borodkin, V. S. & van Aalten, D. M. Human OGA binds substrates in a conserved peptide recognition groove. Biochem. J. 432, 1-7 (2010).
47. Kim, E. J. Chemical arsenal for the study of O-GlcNAc. Molecules 16, 1987-2022 (2011).
48. Comtesse, N., Maldener, E. & Meese, E. Identification of a nuclear variant of MGEA5, a cytoplasmic hyaluronidase and a β-N- acetylglucosaminidase. Biochem. Biophys. Res. Commun. 283, 634-640 (2001). (Pubitemid 32917936)
49. Hanover, J. A. et al. A Caenorhabditis elegans model of insulin resistance: altered macronutrient storage and dauer formation in an OGT-1 knockout. Proc. Natl Acad. Sci. USA 102, 11266-11271 (2005). (Pubitemid 41153809)
50. Forsythe, M. E. et al. Caenorhabditis elegans ortholog of a diabetes susceptibility locus: oga1 (O-GlcNAcase) knockout impacts O-GlcNAc cycling, metabolism, and dauer. Proc. Natl Acad. Sci. USA 103, 11952-11957 (2006). (Pubitemid 44215792)
51. Mondoux, M. A. et al. O-linked N-acetylglucosamine cycling and insulin signaling are required for the glucose stress response in Caenorhabditis elegans. Genetics 188, 369-382 (2011).
52. Rahman, M. M. et al. Intracellular protein glycosylation modulates insulin mediated lifespan in C. elegans. Aging (Albany NY) 2, 678-690 (2010).
53. Ingham, P. W. A gene that regulates the bithorax complex differentially in larval and adult cells of Drosophila. Cell 37, 815-823 (1984). (Pubitemid 15139279)
54. Shafi, R. et al. 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, 5735-5739 (2000). (Pubitemid 30367467)
55. O'Donnell, N., Zachara, N. E., Hart, G. W. & Marth, J. D. Ogt-dependent X-chromosome-linked protein glycosylation is a requisite modification in somatic cell function and embryo viability. Mol. Cell. Biol. 24, 1680-1690 (2004). (Pubitemid 38167089)
56. Chalkley, R. J., Thalhammer, A., Schoepfer, R. & Burlingame, A. L. Identification of protein O-GlcNAcylation sites using electron transfer dissociation mass spectrometry on native peptides. Proc. Natl Acad. Sci. USA 106, 8894-8899 (2009).
57. Musicki, B., Kramer, M. F., Becker, R. E. & Burnett, A. L. Inactivation of phosphorylated endothelial nitric oxide synthase (Ser1177) by O-GlcNAc in diabetes-associated erectile dysfunction. Proc. Natl Acad. Sci. USA 102, 11870-11875 (2005). (Pubitemid 41170817)
58. Dentin, R., Hedrick, S., Xie, J., Yates, J. 3rd & Montminy, M. Hepatic glucose sensing via the CREB coactivator CRTC2. Science 319, 1402-1405 (2008). (Pubitemid 351354877)
59. Rexach, J. E. et al. Dynamic O-GlcNAc modification regulates CREB-mediated gene expression and memory formation. Nature Chem. Biol. 8, 253-261 (2012).
60. Li, M. D. et al. O-GlcNAc transferase is involved in glucocorticoid receptor-mediated transrepression. J. Biol. Chem. 27 Feb 2012 (doi:10.1074/jbc. M111.303792).
61. Kristie, T. M., Liang, Y. & Vogel, J. L. Control of α-herpesvirus IE gene expression by HCF1 coupled chromatin modification activities. Biochim. Biophys. Acta 1799, 257-265 (2010).
62. Goto, H. et al. A single-point mutation in HCF causes temperature-sensitive cell-cycle arrest and disrupts VP16 function. Genes Dev. 11, 726-737 (1997). (Pubitemid 27157161)
63. Hanover, J. A. A versatile sugar transferase makes the cut. Cell 144, 321-323 (2011).
64. Wysocka, J., Myers, M. P., Laherty, C. D., Eisenman, R. N. & Herr, W. Human Sin3 deacetylase and trithorax-related Set1/Ash2 histone H3K4 methyltransferase are tethered together selectively by the cell-proliferation factor HCF1. Genes Dev. 17, 896-911 (2003). (Pubitemid 36397377)
65. Yang, X., Zhang, F. & Kudlow, J. E. Recruitment of O-GlcNAc transferase to promoters by corepressor mSin3A: coupling protein O-GlcNAcylation to transcriptional repression. Cell 110, 69-80 (2002). (Pubitemid 34874607)
66. Sakabe, K. & Hart, G. W. O-GlcNAc transferase regulates mitotic chromatin dynamics. J. Biol. Chem. 285, 34460-34468 (2010).
67. Myers, S. A., Panning, B. & Burlingame, A. L. Polycomb repressive complex 2 is necessary for the normal site-specific O-GlcNAc distribution in mouse embryonic stem cells. Proc. Natl Acad. Sci. USA 108, 9490-9495 (2011).
68. Fong, J. J. et al. β-N-acetylglucosamine (O-GlcNAc) is a novel regulator of mitosis-specific phosphorylations on histone H3. J. Biol. Chem. 27 Feb 2012 (doi: 10.1074/jbc.M111.315804).
69. Maurange, C. & Paro, R. A cellular memory module conveys epigenetic inheritance of hedgehog expression during Drosophila wing imaginal disc development. Genes Dev. 16, 2672-2683 (2002).
70. Breen, T. R. & Duncan, I. M. Maternal expression of genes that regulate the bithorax complex of Drosophila melanogaster. Dev. Biol. 118, 442-456 (1986).
71. Cheng, N. N., Sinclair, D. A., Campbell, R. B. & Brock, H. W. Interactions of polyhomeotic with Polycomb group genes of Drosophila melanogaster. Genetics 138, 1151-1162 (1994). (Pubitemid 24375261)
72. Campbell, R. B., Sinclair, D. A., Couling, M. & Brock, H. W. Genetic interactions and dosage effects of Polycomb group genes of Drosophila. Mol. Gen. Genet. 246, 291-300 (1995).
73. Gildea, J. J., Lopez, R. & Shearn, A. A screen for new trithorax group genes identified little imaginal discs, the Drosophila melanogaster homologue of human retinoblastoma binding protein 2. Genetics 156, 645-663 (2000).
74. Chikanishi, T. et al. Glucose-induced expression of MIP1 genes requires O-GlcNAc transferase in monocytes. Biochem. Biophys. Res. Commun. 394, 865-870 (2010).
75. Fujiki, R. et al. GlcNAcylation of a histone methyltransferase in retinoic-acid-induced granulopoiesis. Nature 459, 455-459 (2009).
76. Nimura, K. et al. A histone H3 lysine 36 trimethyltransferase links Nkx 2-5 to Wolf-Hirschhorn syndrome. Nature 460, 287-291 (2009).
77. Cheung, W. D., Sakabe, K., Housley, M. P., Dias, W. B. & Hart, G. W. O-linked β-N-acetylglucosaminyltransferase substrate specificity is regulated by myosin phosphatase targeting and other interacting proteins. J. Biol. Chem. 283, 33935-33941 (2008).
78. Dejosez, M. et al. Ronin is essential for embryogenesis and the pluripotency of mouse embryonic stem cells. Cell 133, 1162-1174 (2008). (Pubitemid 351852919)
79. Dejosez, M. et al. Ronin/Hcf1 binds to a hyperconserved enhancer element and regulates genes involved in the growth of embryonic stem cells. Genes Dev. 24, 1479-1484 (2010).
80. Lemischka, I. R. Hooking up with Oct4. Cell Stem Cell 6, 291-292 (2010).
81. Pardo, M. et al. An expanded Oct4 interaction network: implications for stem cell biology, development, and disease. Cell Stem Cell 6, 382-395 (2010).
82. Van den Berg, D. L. et al. An Oct4-centered protein interaction network in embryonic stem cells. Cell Stem Cell 6, 369-381 (2010).
83. Boyer, L. A. et al. Core transcriptional regulatory circuitry in human embryonic stem cells. Cell 122, 947-956 (2005). (Pubitemid 41345211)
84. Lee, T. I. et al. Control of developmental regulators by Polycomb in human embryonic stem cells. Cell 125, 301-313 (2006). (Pubitemid 44313811)
85. Kim, H. S. et al. Excessive O-GlcNAcylation of proteins suppresses spontaneous cardiogenesis in ES cells. FEBS Lett. 583, 2474-2478 (2009).
86. Escamilla-Del-Arenal, M., da Rocha, S. T. & Heard, E. Evolutionary diversity and developmental regulation of Xchromosome inactivation. Hum. Genet. 130, 307-327 (2011).
87. Lin, H. et al. Dosage compensation in the mouse balances up-regulation and silencing of X-linked genes. PLoS Biol. 5, e326 (2007).
88. Donohoe, M. E., Silva, S. S., Pinter, S. F., Xu, N. & Lee, J. T. The pluripotency factor Oct4 interacts with Ctcf and also controls X-chromosome pairing and counting. Nature 460, 128-132 (2009).
89. Wang, J. et al. Imprinted X inactivation maintained by a mouse Polycomb group gene. Nature Genet. 28, 371-375 (2001). (Pubitemid 32702428)
90. Ringrose, L. & Paro, R. Epigenetic regulation of cellular memory by the Polycomb and Trithorax group proteins. Annu. Rev. Genet. 38, 413-443 (2004). (Pubitemid 40013734)
91. Schuettengruber, B., Chourrout, D., Vervoort, M., Leblanc, B. & Cavalli, G. Genome regulation by polycomb and trithorax proteins. Cell 128, 735-745 (2007). (Pubitemid 46273581)
92. Ringrose, L. & Paro, R. Polycomb/Trithorax response elements and epigenetic memory of cell identity. Development 134, 223-232 (2007).
93. Lee, J. Molecular links between X-inactivation and autosomal imprinting: X-inactivation as a driving force for the evolution of imprinting? Curr. Biol. 13, R242-R254 (2003). (Pubitemid 36352348)
94. Waddington, C. H. Canalization of development and genetic assimilation of acquired characters. Nature 183, 1654-1655 (1959).
95. Neel, J. V. Diabetes mellitus: a "thrifty" genotype rendered detrimental by "progress"? Am. J. Hum. Genet. 14, 353-362 (1962).
96. Hales, C. N. & Barker, D. J. Type 2 (non-insulin-dependent) diabetes mellitus: the thrifty phenotype hypothesis. Diabetologia 35, 595-601 (1992).
97. Hales, C. N. & Barker, D. J. The thrifty phenotype hypothesis. Br. Med. Bull. 60, 5-20 (2001). (Pubitemid 34123501)
98. McClain, D. A. et al. Altered glycan-dependent signaling induces insulin resistance and hyperleptinemia. Proc. Natl Acad. Sci. USA 99, 10695-10699 (2002).
99. Vosseller, K., Wells, L., Lane, M. D. & Hart, G. W. Elevated nucleocytoplasmic glycosylation by O-GlcNAc results in insulin resistance associated with defects in Akt activation in 3T3L1 adipocytes. Proc. Natl Acad. Sci. USA 99, 5313-5318 (2002). (Pubitemid 34411545)
100. Sekine, O., Love, D. C., Rubenstein, D. S. & Hanover, J. A. Blocking O-linked GlcNAc cycling in Drosophila insulin-producing cells perturbs glucose-insulin homeostasis. J. Biol. Chem. 285, 38684-38691 (2010).
101. Yang, X. et al. Phosphoinositide signalling links O-GlcNAc transferase to insulin resistance. Nature 451, 964-969 (2008). (Pubitemid 351301737)
102. Cameron, E. A. et al. MGEA5-14 polymorphism and type 2 diabetes in Mexico City. Am. J. Hum. Biol. 19, 593-596 (2007). (Pubitemid 47050096)
103. Lehman, D. M. et al. A single nucleotide polymorphism in MGEA5 encoding O-GlcNAc-selective N-acetyl-β-D glucosaminidase is associated with type 2 diabetes in Mexican Americans. Diabetes 54, 1214-1221 (2005). (Pubitemid 40446339)
104. Pettitt, D. J. & Jovanovic, L. The vicious cycle of diabetes and pregnancy. Curr. Diab. Rep. 7, 295-297 (2007). (Pubitemid 47249088)
105. Yuzwa, S. A. et al. A potent mechanism-inspired O-GlcNAcase inhibitor that blocks phosphorylation of tau in vivo. Nature Chem. Biol. 4, 483-490 (2008).
106. Dias, W. B. & Hart, G. W. O-GlcNAc modification in diabetes and Alzheimer's disease. Mol. Biosyst. 3, 766-772 (2007). (Pubitemid 47587186)
107. Lazarus, B. D., Love, D. C. & Hanover, J. A. O-GlcNAc cycling: implications for neurodegenerative disorders. Int. J. Biochem. Cell Biol. 41, 2134-2146 (2009).
108. Housley, M. P. et al. O-GlcNAc regulates FoxO activation in response to glucose. J. Biol. Chem. 283, 16283-16292 (2008).
109. Chou, T. Y., Hart, G. W. & Dang, C. V. cMyc is glycosylated at threonine 58, a known phosphorylation site and a mutational hot spot in lymphomas. J. Biol. Chem. 270, 18961-18965 (1995).
110. Gewinner, C. et al. The coactivator of transcription CREB-binding protein interacts preferentially with the glycosylated form of Stat5. J. Biol. Chem. 279, 3563-3572 (2004). (Pubitemid 38140596)
111. Tarrant, M. K. et al. Regulation of CK2 by phosphorylation and O-GlcNAcylation revealed by semisynthesis. Nature Chem. Biol. 8, 262-269 (2012).
112. Ayer, D. E., Lawrence, Q. A. & Eisenman, R. N. Mad-Max transcriptional repression is mediated by ternary complex formation with mammalian homologs of yeast repressor Sin3. Cell 80, 767-776 (1995).