A little sugar goes a long way: The cell biology of O-GlcNAc

Journal of Cell Biology

Volumn 208, Issue 7, 2015, Pages 869-880

  Bond, Michelle R ^a   Hanover, John A ^a  

^a NONE

Author keywords

[No Author keywords available]

Indexed keywords

HEXOSAMINE; N ACETYLGLUCOSAMINE; O LINKED BETA N ACETYL GLUCOSAMINE; UNCLASSIFIED DRUG; ISOPROTEIN; N ACETYLGLUCOSAMINYLTRANSFERASE; O-GLCNAC TRANSFERASE; UDP-N-ACETYLGLUCOSAMINE-PEPTIDE BETA-N-ACETYLGLUCOSAMINYLTRANSFERASE; URIDINE DIPHOSPHATE;

ALTERNATIVE RNA SPLICING; APOPTOSIS; ARTICLE; CAENORHABDITIS ELEGANS; CARBOHYDRATE SYNTHESIS; CARBOXY TERMINAL SEQUENCE; ENZYME ACTIVITY; HUMAN; IN VITRO STUDY; INTRON; MASS SPECTROMETRY; MEMBRANE PERMEABILITY; MICHAELIS CONSTANT; MITOCHONDRIAL GENOME; PRIORITY JOURNAL; PROTEIN FUNCTION; PROTEIN PHOSPHORYLATION; PROTEIN PROCESSING; PROTEIN SECONDARY STRUCTURE; TETRATRICOPEPTIDE REPEAT; ANALOGS AND DERIVATIVES; ANIMAL; BIOSYNTHESIS; CELL NUCLEUS; CHEMISTRY; CYTOPLASM; GENETICS; METABOLISM; MITOCHONDRION; STEM CELL;

ACETYLGLUCOSAMINE; ALTERNATIVE SPLICING; ANIMALS; CELL NUCLEUS; CYTOPLASM; HUMANS; MITOCHONDRIA; N-ACETYLGLUCOSAMINYLTRANSFERASES; PROTEIN ISOFORMS; PROTEIN PROCESSING, POST-TRANSLATIONAL; STEM CELLS; URIDINE DIPHOSPHATE;

EID: 84928254126     PISSN: 00219525     EISSN: 15408140     Source Type: Journal    
DOI: 10.1083/jcb.201501101     Document Type: Article

References (142)

1. Aguilera, A., and F.K. Zimmermann. 1986. Isolation and molecular analysis of the phosphoglucose isomerase structural gene of Saccharomyces cerevisiae. Mol. Gen. Genet. 202:83-89. http://dx.doi.org/10.1007/BF00330521
2. Barnes, V.L., B.S. Strunk, I. Lee, M. Hüttemann, and L.A. Pile. 2010. Loss of the SIN3 transcriptional corepressor results in aberrant mitochondrial function. BMC Biochem. 11:26. http://dx.doi.org/10.1186/1471-2091-11-26
3. Bauer, C., K. Göbel, N. Nagaraj, C. Colantuoni, M. Wang, U. Müller, E. Kremmer, A. Rottach, and H. Leonhardt. 2015. Phosphorylation of TET proteins is regulated via O-GlcNAcylation by the O-linked N-acetylglucosamine transferase (OGT). J. Biol. Chem. 290:4801-4812. http://dx.doi.org/10.1074/jbc.M114.605881
4. Blatch, G.L., and M. Lässle. 1999. The tetratricopeptide repeat: a structural motif mediating protein-protein interactions. BioEssays. 21:932-939. http://dx.doi.org/10.1002/(SICI)1521-1878(199911)21:11<932::AID-BIES5> 3.0.CO;2-N
5. Boehmelt, G., I. Fialka, G. Brothers, M.D. McGinley, S.D. Patterson, R. Mo, C.C. Hui, S. Chung, L.A. Huber, T.W. Mak, and N.N. Iscove. 2000a. Cloning and characterization of the murine glucosamine-6-phosphate acetyltransferase EMeg32. Differential expression and intracellular membrane association. J. Biol. Chem. 275:12821-12832. http://dx.doi.org/10.1074/jbc.275.17.12821
6. Boehmelt, G., A. Wakeham, A. Elia, T. Sasaki, S. Plyte, J. Potter, Y. Yang, E. Tsang, J. Ruland, N.N. Iscove, et al. 2000b. Decreased UDP-GlcNAc levels abrogate proliferation control in EMeg32-deficient cells. EMBO J. 19:5092-5104. http://dx.doi.org/10.1093/emboj/19.19.5092
7. Bond, M.R., and J.A. Hanover. 2013. O-GlcNAc cycling: a link between metabolism and chronic disease. Annu. Rev. Nutr. 33:205-229. http://dx.doi .org/10.1146/annurev-nutr-071812-161240
8. Brickley, K., K. Pozo, and F.A. Stephenson. 2011. N-acetylglucosamine transferase is an integral component of a kinesin-directed mitochondrial trafficking complex. Biochim. Biophys. Acta. 1813:269-281. http://dx.doi .org/10.1016/j.bbamcr.2010.10.011
9. Bueding, E., and J.A. MacKinnon. 1955. Hexokinases of Schistosoma mansoni. J. Biol. Chem. 215:495-506.
10. Bullen, J.W., J.L. Balsbaugh, D. Chanda, J. Shabanowitz, D.F. Hunt, D. Neumann, and G.W. Hart. 2014. Cross-talk between two essential nutrient-sensitive enzymes: O-GlcNAc transferase (OGT) and AMP-activated protein kinase (AMPK). J. Biol. Chem. 289:10592-10606. http://dx.doi.org/10.1074/jbc.M113.523068
11. Butkinaree, C., W.D. Cheung, S. Park, K. Park, M. Barber, and G.W. Hart. 2008. Characterization of β-N-acetylglucosaminidase cleavage by caspase-3 during apoptosis. J. Biol. Chem. 283:23557-23566. http://dx.doi.org/10.1074/jbc.M804116200
12. Butkinaree, C., K. Park, and G.W. Hart. 2010. 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. http://dx.doi.org/10.1016/j.bbagen.2009.07.018
13. Capotosti, F., S. Guernier, F. Lammers, P. Waridel, Y. Cai, J. Jin, J.W. Conaway, R.C. Conaway, and W. Herr. 2011. O-GlcNAc transferase catalyzes sitespecific proteolysis of HCF-1. Cell. 144:376-388. http://dx.doi.org/10.1016/j.cell.2010.12.030
14. Çetinbas, N., M.S. Macauley, K.A. Stubbs, R. Drapala, and D.J. Vocadlo. 2006. Identification of Asp174 and Asp175 as the key catalytic residues of human O-GlcNAcase by functional analysis of site-directed mutants. Biochemistry. 45:3835-3844. http://dx.doi.org/10.1021/bi052370b
15. Charoensuksai, P., P. Kuhn, L. Wang, N. Sherer, and W. Xu. 2015. O-GlcNAcylation of co-activator-associated arginine methyltransferase 1 regulates its protein substrate specificity. Biochem. J. 466:587-599. http://dx.doi.org/10.1042/BJ20141072
16. Chen, Q., Y. Chen, C. Bian, R. Fujiki, and X. Yu. 2013. TET2 promotes histone O-GlcNAcylation during gene transcription. Nature. 493:561-564. http://dx.doi.org/10.1038/nature11742
17. Chen, Y.X., J.T. Du, L.X. Zhou, X.H. Liu, Y.F. Zhao, H. Nakanishi, and Y.M. Li. 2006. Alternative O-GlcNAcylation/O-phosphorylation of Ser16 induce different conformational disturbances to the N terminus of murine estrogen receptor beta. Chem. Biol. 13:937-944. http://dx.doi.org/10.1016/j.chembiol.2006.06.017
18. Cheung, W.D., and G.W. Hart. 2008. AMP-activated protein kinase and p38 MAPK activate O-GlcNAcylation of neuronal proteins during glucose deprivation. J. Biol. Chem. 283:13009-13020. http://dx.doi.org/10.1074/jbc.M801222200
19. Comer, F.I., and G.W. Hart. 2001. Reciprocity between O-GlcNAc and O-phosphate on the carboxyl terminal domain of RNA polymerase II. Biochemistry. 40:7845-7852. http://dx.doi.org/10.1021/bi0027480
20. Comtesse, N., E. Maldener, and E. Meese. 2001. Identification of a nuclear variant of MGEA5, a cytoplasmic hyaluronidase and a beta-N-acetylglucosaminidase. Biochem. Biophys. Res. Commun. 283:634-640. http://dx.doi .org/10.1006/bbrc.2001.4815
21. Dassanayaka, S., R.D. Readnower, J.K. Salabei, B.W. Long, A.L. Aird, Y.T. Zheng, S. Muthusamy, H.T. Facundo, B.G. Hill, and S.P. Jones. 2015. High glucose induces mitochondrial dysfunction independent of protein O-GlcNAcylation. Biochem. J. http://dx.doi.org/10.1042/BJ20141018
22. Deplus, R., B. Delatte, M.K. Schwinn, M. Defrance, J. Méndez, N. Murphy, M.A. Dawson, M. Volkmar, P. Putmans, E. Calonne, et al. 2013. TET2 and TET3 regulate GlcNAcylation and H3K4 methylation through OGT and SET1/COMPASS. EMBO J. 32:645-655. http://dx.doi.org/10.1038/emboj.2012.357
23. D'Onofrio, M., C.M. Starr, M.K. Park, G.D. Holt, R.S. Haltiwanger, G.W. Hart, and J.A. Hanover. 1988. Partial cDNA sequence encoding a nuclear pore protein modified by O-linked N-acetylglucosamine. Proc. Natl. Acad. Sci. USA. 85:9595-9599. http://dx.doi.org/10.1073/pnas.85.24.9595
24. Dorfmueller, H.C., V.S. Borodkin, M. Schimpl, S.M. Shepherd, N.A. Shpiro, and D.M. van Aalten. 2006. GlcNAcstatin: a picomolar, selective O-GlcNAcase inhibitor that modulates intracellular O-glcNAcylation levels. J. Am. Chem. Soc. 128:16484-16485. http://dx.doi.org/10.1021/ja066743n Einstein, F.H., G. Atzmon, X.M. Yang, X.H. Ma, M. Rincon, E. Rudin, R.
25. Einstein, F.H., G. Atzmon, X.M. Yang, X.H. Ma, M. Rincon, E. Rudin, R. Muzumdar, and N. Barzilai. 2005. Differential responses of visceral and subcutaneous fat depots to nutrients. Diabetes. 54:672-678. http://dx.doi .org/10.2337/diabetes.54.3.672
26. Erickson, J.R., L. Pereira, L. Wang, G. Han, A. Ferguson, K. Dao, R.J. Copeland, F. Despa, G.W. Hart, C.M. Ripplinger, and D.M. Bers. 2013. Diabetic hyperglycaemia activates CaMKII and arrhythmias by O-linked glycosylation. Nature. 502:372-376. http://dx.doi.org/10.1038/nature12537
27. Fang, B., and M.W. Miller. 2001. Use of galactosyltransferase to assess the biological function of O-linked N-acetyl-d-glucosamine: a potential role for O-GlcNAc during cell division. Exp. Cell Res. 263:243-253. http:// dx.doi.org/10.1006/excr.2000.5110
28. Federici, M., R. Menghini, A. Mauriello, M.L. Hribal, F. Ferrelli, D. Lauro, P. Sbraccia, L.G. Spagnoli, G. Sesti, and R. Lauro. 2002. Insulin-dependent activation of endothelial nitric oxide synthase is impaired by O-linked glycosylation modification of signaling proteins in human coronary endothelial cells. Circulation. 106:466-472. http://dx.doi.org/10.1161/01.CIR.0000023043.02648.51
29. Ferrer, C.M., T.P. Lynch, V.L. Sodi, J.N. Falcone, L.P. Schwab, D.L. Peacock, D.J. Vocadlo, T.N. Seagroves, and M.J. Reginato. 2014. O-GlcNAcylation regulates cancer metabolism and survival stress signaling via regulation of the HIF-1 pathway. Mol. Cell. 54:820-831. http://dx.doi.org/10.1016/j.molcel.2014.04.026
30. Folmes, C.D., P.P. Dzeja, T.J. Nelson, and A. Terzic. 2012. Metabolic plasticity in stem cell homeostasis and differentiation. Cell Stem Cell. 11:596-606. http://dx.doi.org/10.1016/j.stem.2012.10.002
31. Forsythe, M.E., D.C. Love, B.D. Lazarus, E.J. Kim, W.A. Prinz, G. Ashwell, M.W. Krause, and J.A. Hanover. 2006. Caenorhabditis elegans ortholog of a diabetes susceptibility locus: oga-1 (O-GlcNAcase) knockout impacts O-GlcNAc cycling, metabolism, and dauer. Proc. Natl. Acad. Sci. USA. 103:11952-11957. http://dx.doi.org/10.1073/pnas.0601931103
32. Gambetta, M.C., and J. Müller. 2014. O-GlcNAcylation prevents aggregation of the Polycomb group repressor polyhomeotic. Dev. Cell. 31:629-639. http://dx.doi.org/10.1016/j.devcel.2014.10.020
33. Gambetta, M.C., K. Oktaba, and J. Müller. 2009. Essential role of the glycosyltransferase sxc/Ogt in polycomb repression. Science. 325:93-96. http://dx.doi.org/10.1126/science.1169727
34. Gao, Y., L. Wells, F.I. Comer, G.J. Parker, and G.W. Hart. 2001. Dynamic O-glycosylation of nuclear and cytosolic proteins: cloning and characterization of a neutral, cytosolic beta-N-acetylglucosaminidase from human brain. J. Biol. Chem. 276:9838-9845. http://dx.doi.org/10.1074/jbc.M010420200
35. Gawlowski, T., J. Suarez, B. Scott, M. Torres-Gonzalez, H. Wang, R. Schwappacher, X. Han, J.R. Yates III, M. Hoshijima, and W. Dillmann. 2012. Modulation of dynamin-related protein 1 (DRP1) function by increased O-linked-β-N-acetylglucosamine modification (O-GlcNAc) in cardiac myocytes. J. Biol. Chem. 287:30024-30034. http://dx.doi.org/10.1074/jbc.M112.390682
36. Ghosh, S.K., M.R. Bond, D.C. Love, G.G. Ashwell, M.W. Krause, and J.A. Hanover. 2014. Disruption of O-GlcNAc cycling in C. elegans perturbs nucleotide sugar pools and complex glycans. Front. Endocrinol. (Lausanne). 5:197.
37. Guo, B., Q. Liang, L. Li, Z. Hu, F. Wu, P. Zhang, Y. Ma, B. Zhao, A.L. Kovács, Z. Zhang, et al. 2014. O-GlcNAc-modification of SNAP-29 regulates autophagosome maturation. Nat. Cell Biol. 16:1215-1226. http://dx.doi .org/10.1038/ncb3066
38. Ha, J.R., L. Hao, G. Venkateswaran, Y.H. Huang, E. Garcia, and S. Persad. 2014. β-catenin is O-GlcNAc glycosylated at Serine 23: implications for β-catenin's subcellular localization and transactivator function. Exp. Cell Res. 321:153-166. http://dx.doi.org/10.1016/j.yexcr.2013.11.021
39. Haltiwanger, R.S., M.A. Blomberg, and G.W. Hart. 1992. Glycosylation of nuclear and cytoplasmic proteins. Purification and characterization of a uridine diphospho-N-acetylglucosamine:polypeptide beta-N-acetylglucosaminyltransferase. J. Biol. Chem. 267:9005-9013.
40. Hanover, J.A., C.K. Cohen, M.C. Willingham, and M.K. Park. 1987. O-linked N-acetylglucosamine is attached to proteins of the nuclear pore. Evidence for cytoplasmic and nucleoplasmic glycoproteins. J. Biol. Chem. 262: 9887-9894.
41. Hanover, J.A., S. Yu, W.B. Lubas, S.H. Shin, M. Ragano-Caracciola, J. Kochran, and D.C. Love. 2003. Mitochondrial and nucleocytoplasmic isoforms of O-linked GlcNAc transferase encoded by a single mammalian gene. Arch. Biochem. Biophys. 409:287-297. http://dx.doi.org/10.1016/S0003-9861(02)00578-7
42. Hanover, J.A., M.W. Krause, and D.C. Love. 2010. The hexosamine signaling pathway: O-GlcNAc cycling in feast or famine. Biochim. Biophys. Acta. 1800:80-95. http://dx.doi.org/10.1016/j.bbagen.2009.07.017
43. Hanover, J.A., M.W. Krause, and D.C. Love. 2012. Bittersweet memories: linking metabolism to epigenetics through O-GlcNAcylation. Nat. Rev. Mol. Cell Biol. 13:312-321. http://dx.doi.org/10.1038/nrm3334
44. Hardivillé, S., and G.W. Hart. 2014. Nutrient regulation of signaling, transcription, and cell physiology by O-GlcNAcylation. Cell Metab. 20:208-213. http://dx.doi.org/10.1016/j.cmet.2014.07.014
45. Hart, G.W. 2014. Minireview series on the thirtieth anniversary of research on O-GlcNAcylation of nuclear and cytoplasmic proteins: Nutrient regulation of cellular metabolism and physiology by O-GlcNAcylation. J. Biol. Chem. 289:34422-34423. http://dx.doi.org/10.1074/jbc.R114.609776
46. He, Y., C. Roth, J.P. Turkenburg, and G.J. Davies. 2014. Three-dimensional structure of a Streptomyces sviceus GNAT acetyltransferase with similarity to the C-terminal domain of the human GH84 O-GlcNAcase. Acta Crystallogr. D Biol. Crystallogr. 70:186-195.
47. Heckel, D., N. Comtesse, N. Brass, N. Blin, K.D. Zang, and E. Meese. 1998. Novel immunogenic antigen homologous to hyaluronidase in meningioma. Hum. Mol. Genet. 7:1859-1872. http://dx.doi.org/10.1093/hmg/7.12.1859
48. Hinderlich, S., M. Berger, M. Schwarzkopf, K. Effertz, and W. Reutter. 2000. Molecular cloning and characterization of murine and human N-acetylglucosamine kinase. Eur. J. Biochem. 267:3301-3308. http://dx.doi.org/10.1046/j.1432-1327.2000.01360.x
49. Hofmann, M., E. Boles, and F.K. Zimmermann. 1994. Characterization of the essential yeast gene encoding N-acetylglucosamine-phosphate mutase. Eur. J. Biochem. 221:741-747. http://dx.doi.org/10.1111/j.1432-1033.1994.tb18787.x Holt, G.D., C.M. Snow, A. Senior, R.S. Haltiwanger, L. Gerace, and G.W.
50. Holt, G.D., C.M. Snow, A. Senior, R.S. Haltiwanger, L. Gerace, and G.W. Hart. 1987. Nuclear pore complex glycoproteins contain cytoplasmically disposed O-linked N-acetylglucosamine. J. Cell Biol. 104:1157-1164. http://dx.doi.org/10.1083/jcb.104.5.1157
51. Howerton, C.L., and T.L. Bale. 2014. Targeted placental deletion of OGT recapitulates the prenatal stress phenotype including hypothalamic mitochondrial dysfunction. Proc. Natl. Acad. Sci. USA. 111:9639-9644. http://dx .doi.org/10.1073/pnas.1401203111
52. Howerton, C.L., C.P. Morgan, D.B. Fischer, and T.L. Bale. 2013. O-GlcNAc transferase (OGT) as a placental biomarker of maternal stress and reprogramming of CNS gene transcription in development. Proc. Natl. Acad. Sci. USA. 110:5169-5174. http://dx.doi.org/10.1073/pnas.1300065110
53. Hu, Y., J. Suarez, E. Fricovsky, H. Wang, B.T. Scott, S.A. Trauger, W. Han, Y. Hu, M.O. Oyeleye, and W.H. Dillmann. 2009. Increased enzymatic OGlcNAcylation of mitochondrial proteins impairs mitochondrial function in cardiac myocytes exposed to high glucose. J. Biol. Chem. 284:547-555. http://dx.doi.org/10.1074/jbc.M808518200
54. Ingham, P.W. 1984. A gene that regulates the bithorax complex differentially in larval and adult cells of Drosophila. Cell. 37:815-823. http://dx.doi .org/10.1016/0092-8674(84)90416-1
55. Ito, R., S. Katsura, H. Shimada, H. Tsuchiya, M. Hada, T. Okumura, A. Sugawara, and A. Yokoyama. 2014. TET3-OGT interaction increases the stability and the presence of OGT in chromatin. Genes Cells. 19:52-65. http://dx.doi.org/10.1111/gtc.12107
56. Iyer, S.P., Y. Akimoto, and G.W. Hart. 2003. Identification and cloning of a novel family of coiled-coil domain proteins that interact with O-GlcNAc transferase. J. Biol. Chem. 278:5399-5409. http://dx.doi.org/10.1074/jbc .M209384200
57. Janetzko, J., and S. Walker. 2014. The making of a sweet modification: structure and function of O-GlcNAc transferase. J. Biol. Chem. 289:34424-34432. http://dx.doi.org/10.1074/jbc.R114.604405
58. Jang, H., T.W. Kim, S. Yoon, S.Y. Choi, T.W. Kang, S.Y. Kim, Y.W. Kwon, E.J. Cho, and H.D. Youn. 2012. O-GlcNAc regulates pluripotency and reprogramming by directly acting on core components of the pluripotency network. Cell Stem Cell. 11:62-74. http://dx.doi.org/10.1016/j.stem.2012.03.001
59. Jínek, M., J. Rehwinkel, B.D. Lazarus, E. Izaurralde, J.A. Hanover, and E. Conti. 2004. The superhelical TPR-repeat domain of O-linked GlcNAc transferase exhibits structural similarities to importin alpha. Nat. Struct. Mol. Biol. 11:1001-1007. http://dx.doi.org/10.1038/nsmb833
60. Johnsen, V.L., D.D. Belke, C.C. Hughey, D.S. Hittel, R.T. Hepple, L.G. Koch, S.L. Britton, and J. Shearer. 2013. Enhanced cardiac protein glycosylation (O-GlcNAc) of selected mitochondrial proteins in rats artificially selected for low running capacity. Physiol. Genomics. 45:17-25. http://dx.doi.org/10.1152/physiolgenomics.00111.2012
61. Kadamb, R., S. Mittal, N. Bansal, H. Batra, and D. Saluja. 2013. Sin3: insight into its transcription regulatory functions. Eur. J. Cell Biol. 92:237-246. http://dx.doi.org/10.1016/j.ejcb.2013.09.001
62. Keembiyehetty, C.N., A. Krzeslak, D.C. Love, and J.A. Hanover. 2011. A lipiddroplet-targeted O-GlcNAcase isoform is a key regulator of the proteasome. J. Cell Sci. 124:2851-2860. http://dx.doi.org/10.1242/jcs.083287
63. Keembiyehetty, C., D.C. Love, K.R. Harwood, O. Gavrilova, M.E. Comly, and J.A. Hanover. 2015. Conditional knockout reveals a requirement for OGlcNAcase in metabolic homeostasis. J. Biol. Chem. http:jbc.M114.617779. http://dx.doi.org/10.1074/jbc.M114.617779
64. Kelly, W.G., M.E. Dahmus, and G.W. Hart. 1993. RNA polymerase II is a glycoprotein. Modification of the COOH-terminal domain by O-GlcNAc. J. Biol. Chem. 268:10416-10424.
65. Kim, E.J., D.O. Kang, D.C. Love, and J.A. Hanover. 2006. Enzymatic characterization of O-GlcNAcase isoforms using a fluorogenic GlcNAc substrate. Carbohydr. Res. 341:971-982. http://dx.doi.org/10.1016/j.carres .2006.03.004
66. Kim, E.J., M.R. Bond, D.C. Love, and J.A. Hanover. 2014. Chemical tools to explore nutrient-driven O-GlcNAc cycling. Crit. Rev. Biochem. Mol. Biol. 49:327-342. http://dx.doi.org/10.3109/10409238.2014.931338
67. Kreppel, L.K., M.A. Blomberg, and G.W. Hart. 1997. 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. http://dx.doi.org/10.1074/jbc.272.14.9308
68. Kumar, A., P.K. Singh, R. Parihar, V. Dwivedi, S.C. Lakhotia, and S. Ganesh. 2014. Decreased O-linked GlcNAcylation protects from cytotoxicity mediated by huntingtin exon1 protein fragment. J. Biol. Chem. 289:13543-13553. http://dx.doi.org/10.1074/jbc.M114.553321
69. Kumari, M., S. Kozmon, P. Kulhanek, J. Stepan, I. Tvaroska, and J. Koča. 2015. Exploring Reaction Pathways for O-GlcNAc transferase catalysis. A string method study. J. Phys. Chem. B. http://dx.doi.org/10.1021/jp511235f
70. Labokha, A.A., S. Gradmann, S. Frey, B.B. Hülsmann, H. Urlaub, M. Baldus, and D. Görlich. 2013. Systematic analysis of barrier-forming FG hydrogels from Xenopus nuclear pore complexes. EMBO J. 32:204-218. http://dx.doi.org/10.1038/emboj.2012.302
71. Lazarus, B.D., D.C. Love, and J.A. Hanover. 2006. Recombinant O-GlcNAc transferase isoforms: identification of O-GlcNAcase, yes tyrosine kinase, and tau as isoform-specific substrates. Glycobiology. 16:415-421. http:// dx.doi.org/10.1093/glycob/cwj078
72. Lazarus, M.B., Y. Nam, J. Jiang, P. Sliz, and S. Walker. 2011. Structure of human O-GlcNAc transferase and its complex with a peptide substrate. Nature. 469:564-567. http://dx.doi.org/10.1038/nature09638
73. Leehey, D.J., A.K. Singh, N. Alavi, and R. Singh. 2000. Role of angiotensin II in diabetic nephropathy. Kidney Int. Suppl. 58(Suppl. 77):S93-S98. http://dx.doi.org/10.1046/j.1523-1755.2000.07715.x
74. Lewis, B.A., and J.A. Hanover. 2014. O-GlcNAc and the epigenetic regulation of gene expression. J. Biol. Chem. 289:34440-34448. http://dx.doi .org/10.1074/jbc.R114.595439
75. Love, D.C., J. Kochan, R.L. Cathey, S.H. Shin, and J.A. Hanover. 2003. Mitochondrial and nucleocytoplasmic targeting of O-linked GlcNAc transferase. J. Cell Sci. 116:647-654. http://dx.doi.org/10.1242/jcs.00246
76. Love, D.C., S. Ghosh, M.A. Mondoux, T. Fukushige, P. Wang, M.A. Wilson, W.B. Iser, C.A. Wolkow, M.W. Krause, and J.A. Hanover. 2010a. Dynamic O-GlcNAc cycling at promoters of Caenorhabditis elegans genes regulating longevity, stress, and immunity. Proc. Natl. Acad. Sci. USA. 107: 7413-7418. http://dx.doi.org/10.1073/pnas.0911857107
77. Love, D.C., M.W. Krause, and J.A. Hanover. 2010b. O-GlcNAc cycling: emerging roles in development and epigenetics. Semin. Cell Dev. Biol. 21:646-654. http://dx.doi.org/10.1016/j.semcdb.2010.05.001
78. Lozano, L., R. Lara-Lemus, E. Zenteno, and N. Alvarado-Vásquez. 2014. The mitochondrial O-linked N-acetylglucosamine transferase (mOGT) in the diabetic patient could be the initial trigger to develop Alzheimer disease. Exp. Gerontol. 58:198-202. http://dx.doi.org/10.1016/j.exger.2014.08.008
79. Lubas, W.A., D.W. Frank, M. Krause, and J.A. Hanover. 1997. O-Linked GlcNAc transferase is a conserved nucleocytoplasmic protein containing tetratricopeptide repeats. J. Biol. Chem. 272:9316-9324. http://dx.doi.org/10.1074/jbc.272.14.9316
80. Luo, B., Y. Soesanto, and D.A. McClain. 2008. Protein modification by O-linked GlcNAc reduces angiogenesis by inhibiting Akt activity in endothelial cells. Arterioscler. Thromb. Vasc. Biol. 28:651-657. http://dx.doi.org/10.1161/ATVBAHA.107.159533
81. Ma, J., and G.W. Hart. 2014. O-GlcNAc profiling: from proteins to proteomes. Clin. Proteomics. 11:8. http://dx.doi.org/10.1186/1559-0275-11-8
82. Macauley, M.S., and D.J. Vocadlo. 2009. Enzymatic characterization and inhibition of the nuclear variant of human O-GlcNAcase. Carbohydr. Res. 344:1079-1084. http://dx.doi.org/10.1016/j.carres.2009.04.017
83. Marsh, S.A., P.C. Powell, L.J. Dell'italia, and J.C. Chatham. 2013. Cardiac OGlcNAcylation blunts autophagic signaling in the diabetic heart. Life Sci. 92:648-656. http://dx.doi.org/10.1016/j.lfs.2012.06.011
84. Marshall, S., V. Bacote, and R.R. Traxinger. 1991a. 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.
85. Marshall, S., W.T. Garvey, and R.R. Traxinger. 1991b. New insights into the metabolic regulation of insulin action and insulin resistance: role of glucose and amino acids. FASEB J. 5:3031-3036.
86. März, P., J. Stetefeld, K. Bendfeldt, C. Nitsch, J. Reinstein, R.L. Shoeman, B. Dimitriades-Schmutz, M. Schwager, D. Leiser, S. Ozcan, et al. 2006. Ataxin-10 interacts with O-linked beta-N-acetylglucosamine transferase in the brain. J. Biol. Chem. 281:20263-20270. http://dx.doi.org/10.1074/jbc.M601563200
87. McKnight, G.L., S.L. Mudri, S.L. Mathewes, R.R. Traxinger, S. Marshall, P.O. Sheppard, and P.J. O'Hara. 1992. Molecular cloning, cDNA sequence, and bacterial expression of human glutamine:fructose-6-phosphate amidotransferase. J. Biol. Chem. 267:25208-25212.
88. Mio, T., T. Yabe, M. Arisawa, and H. Yamada-Okabe. 1998. The eukaryotic UDP-N-acetylglucosamine pyrophosphorylases. Gene cloning, protein expression, and catalytic mechanism. J. Biol. Chem. 273:14392-14397. http://dx.doi.org/10.1074/jbc.273.23.14392
89. Musicki, B., M.F. Kramer, R.E. Becker, and A.L. Burnett. 2005. Inactivation of phosphorylated endothelial nitric oxide synthase (Ser-1177) by OGlcNAc in diabetes-associated erectile dysfunction. Proc. Natl. Acad. Sci. USA. 102:11870-11875. http://dx.doi.org/10.1073/pnas.0502488102
90. Nagel, A.K., and L.E. Ball. 2014. O-GlcNAc transferase and O-GlcNAcase: achieving target substrate specificity. Amino Acids. 46:2305-2316. http:// dx.doi.org/10.1007/s00726-014-1827-7
91. Ngoh, G.A., L.J. Watson, H.T. Facundo, W. Dillmann, and S.P. Jones. 2008. Noncanonical glycosyltransferase modulates post-hypoxic cardiac myocyte death and mitochondrial permeability transition. J. Mol. Cell. Cardiol. 45:313-325. http://dx.doi.org/10.1016/j.yjmcc.2008.04.009
92. Ngoh, G.A., T. Hamid, S.D. Prabhu, and S.P. Jones. 2009. O-GlcNAc signaling attenuates ER stress-induced cardiomyocyte death. Am. J. Physiol. Heart Circ. Physiol. 297:H1711-H1719. http://dx.doi.org/10.1152/ajpheart .00553.2009
93. Nishikawa, I., Y. Nakajima, M. Ito, S. Fukuchi, K. Homma, and K. Nishikawa. 2010. Computational prediction of O-linked glycosylation sites that preferentially map on intrinsically disordered regions of extracellular proteins. Int. J. Mol. Sci. 11:4991-5008. http://dx.doi.org/10.3390/ijms11124991
94. Olivier-Van Stichelen, S., and J.A. Hanover. 2014. X-inactivation normalizes O-GlcNAc transferase levels and generates an O-GlcNAc-depleted Barr body. Front. Genet. 5:256. http://dx.doi.org/10.3389/fgene.2014.00256
95. Olivier-Van Stichelen, S., V. Dehennaut, A. Buzy, J.L. Zachayus, C. Guinez, A.M. Mir, I. El Yazidi-Belkoura, M.C. Copin, D. Boureme, D. Loyaux, et al. 2014. O-GlcNAcylation stabilizes β-catenin through direct competition with phosphorylation at threonine 41. FASEB J. 28:3325-3338. http://dx.doi.org/10.1096/fj.13-243535
96. Park, M.K., M. D'Onofrio, M.C. Willingham, and J.A. Hanover. 1987. A monoclonal antibody against a family of nuclear pore proteins (nucleoporins): O-linked N-acetylglucosamine is part of the immunodeterminant. Proc. Natl. Acad. Sci. USA. 84:6462-6466. http://dx.doi.org/10.1073/pnas.84.18.6462
97. Pekkurnaz, G., J.C. Trinidad, X. Wang, D. Kong, and T.L. Schwarz. 2014. Glucose regulates mitochondrial motility via Milton modification by O-GlcNAc transferase. Cell. 158:54-68. http://dx.doi.org/10.1016/j.cell .2014.06.007
98. Phatnani, H.P., and A.L. Greenleaf. 2006. Phosphorylation and functions of the RNA polymerase II CTD. Genes Dev. 20:2922-2936. http://dx.doi .org/10.1101/gad.1477006
99. Ranuncolo, S.M., S. Ghosh, J.A. Hanover, G.W. Hart, and B.A. Lewis. 2012. Evidence of the involvement of O-GlcNAc-modified human RNA polymerase II CTD in transcription in vitro and in vivo. J. Biol. Chem. 287:23549-23561. http://dx.doi.org/10.1074/jbc.M111.330910
100. Rao, F.V., H.C. Dorfmueller, F. Villa, M. Allwood, I.M. Eggleston, and D.M. van Aalten. 2006. Structural insights into the mechanism and inhibition of eukaryotic O-GlcNAc hydrolysis. EMBO J. 25:1569-1578. http:// dx.doi.org/10.1038/sj.emboj.7601026
101. Riu, I.H., I.S. Shin, and S.I. Do. 2008. Sp1 modulates ncOGT activity to alter target recognition and enhanced thermotolerance in E. coli. Biochem. Biophys. Res. Commun. 372:203-209. http://dx.doi.org/10.1016/j.bbrc .2008.05.034
102. Rotty, J.D., G.W. Hart, and P.A. Coulombe. 2010. Stressing the role of OGlcNAc: linking cell survival to keratin modification. Nat. Cell Biol. 12:847-859. http://dx.doi.org/10.1038/ncb0910-847
103. Ryu, I.H., and S.I. Do. 2011. Denitrosylation of S-nitrosylated OGT is triggered in LPS-stimulated innate immune response. Biochem. Biophys. Res. Commun. 408:52-57. http://dx.doi.org/10.1016/j.bbrc.2011.03.115
104. Sakabe, K., Z. Wang, and G.W. Hart. 2010. Beta-N-acetylglucosamine (O-GlcNAc) is part of the histone code. Proc. Natl. Acad. Sci. USA. 107:19915-19920. http://dx.doi.org/10.1073/pnas.1009023107
105. Sassi, A., S. Lazaroski, G. Wu, S.M. Haslam, M. Fliegauf, F. Mellouli, T. Patiroglu, E. Unal, M.A. Ozdemir, Z. Jouhadi, et al. 2014. Hypomorphic homozygous mutations in phosphoglucomutase 3 (PGM3) impair immunity and increase serum IgE levels. J. Allergy Clin. Immunol. 133:1410-1419: e1-e13. http://dx.doi.org/10.1016/j.jaci.2014.02.025
106. Sayat, R., B. Leber, V. Grubac, L. Wiltshire, and S. Persad. 2008. O-GlcNAcglycosylation of beta-catenin regulates its nuclear localization and transcriptional activity. Exp. Cell Res. 314:2774-2787. http://dx.doi.org/10 .1016/j.yexcr.2008.05.017
107. Schimpl, M., A.W. Schüttelkopf, V.S. Borodkin, and D.M. van Aalten. 2010. Human OGA binds substrates in a conserved peptide recognition groove. Biochem. J. 432:1-7. http://dx.doi.org/10.1042/BJ20101338
108. Schimpl, M., V.S. Borodkin, L.J. Gray, and D.M. van Aalten. 2012. Synergy of peptide and sugar in O-GlcNAcase substrate recognition. Chem. Biol. 19:173-178. http://dx.doi.org/10.1016/j.chembiol.2012.01.011
109. Schleicher, E.D., and C. Weigert. 2000. Role of the hexosamine biosynthetic pathway in diabetic nephropathy. Kidney Int. Suppl. 58(Suppl. 77):S13-S18. http://dx.doi.org/10.1046/j.1523-1755.2000.07703.x
110. Schultz, J., and B. Pils. 2002. Prediction of structure and functional residues for O-GlcNAcase, a divergent homologue of acetyltransferases. FEBS Lett. 529:179-182. http://dx.doi.org/10.1016/S0014-5793(02)03322-7
111. Schwartz, M.W., E. Peskind, M. Raskind, E.J. Boyko, and D. Porte Jr. 1996. Cerebrospinal fluid leptin levels: relationship to plasma levels and to adiposity in humans. Nat. Med. 2:589-593. http://dx.doi.org/10.1038/nm0596-589
112. Shen, D.L., T.M. Gloster, S.A. Yuzwa, and D.J. Vocadlo. 2012. Insights into O-linked N-acetylglucosamine ([0-9]O-GlcNAc) processing and dynamics through kinetic analysis of O-GlcNAc transferase and O-GlcNAcase activity on protein substrates. J. Biol. Chem. 287:15395-15408. http://dx.doi.org/10.1074/jbc.M111.310664
113. Shin, S.H., D.C. Love, and J.A. Hanover. 2011. Elevated O-GlcNAc-dependent signaling through inducible mOGT expression selectively triggers apoptosis. Amino Acids. 40:885-893. http://dx.doi.org/10.1007/s00726-010-0719-8
114. Simon, D.N., and M.P. Rout. 2014. Cancer and the nuclear pore complex. Adv. Exp. Med. Biol. 773:285-307. http://dx.doi.org/10.1007/978-1-4899-8032-8_13
115. Sinclair, D.A., M. Syrzycka, M.S. Macauley, T. Rastgardani, I. Komljenovic, D.J. Vocadlo, H.W. Brock, and B.M. Honda. 2009. Drosophila O-GlcNAc transferase (OGT) is encoded by the Polycomb group (PcG) gene, super sex combs (sxc). Proc. Natl. Acad. Sci. USA. 106:13427-13432. http:// dx.doi.org/10.1073/pnas.0904638106
116. Slawson, C., T. Lakshmanan, S. Knapp, and G.W. Hart. 2008. A mitotic GlcNAcylation/phosphorylation signaling complex alters the posttranslational state of the cytoskeletal protein vimentin. Mol. Biol. Cell. 19:4130-4140. http://dx.doi.org/10.1091/mbc.E07-11-1146
117. Snow, C.M., A. Senior, and L. Gerace. 1987. Monoclonal antibodies identify a group of nuclear pore complex glycoproteins. J. Cell Biol. 104:1143-1156. http://dx.doi.org/10.1083/jcb.104.5.1143
118. Srikanth, B., M.M. Vaidya, and R.D. Kalraiya. 2010. O-GlcNAcylation determines the solubility, filament organization, and stability of keratins 8 and 18. J. Biol. Chem. 285:34062-34071. http://dx.doi.org/10.1074/jbc .M109.098996
119. Stachelek, C., J. Stachelek, J. Swan, D. Botstein, and W. Konigsberg. 1986. Identification, cloning and sequence determination of the genes specifying hexokinase A and B from yeast. Nucleic Acids Res. 14:945-963. http://dx.doi.org/10.1093/nar/14.2.945
120. Starr, C.M., and J.A. Hanover. 1990. Glycosylation of nuclear pore protein p62. Reticulocyte lysate catalyzes O-linked N-acetylglucosamine addition in vitro. J. Biol. Chem. 265:6868-6873.
121. Starr, C.M., and J.A. Hanover. 1991. A common structural motif in nuclear pore proteins (nucleoporins). BioEssays. 13:145-146. http://dx.doi.org/ 10.1002/bies.950130309
122. Starr, C.M., M. D'Onofrio, M.K. Park, and J.A. Hanover. 1990. Primary sequence and heterologous expression of nuclear pore glycoprotein p62. J. Cell Biol. 110:1861-1871. http://dx.doi.org/10.1083/jcb.110.6.1861
123. Tan, E.P., M.T. Villar, L. e, J. Lu, J.E. Selfridge, A. Artigues, R.H. Swerdlow, and C. Slawson. 2014. Altering O-linked β-N-acetylglucosamine cycling disrupts mitochondrial function. J. Biol. Chem. 289:14719-14730. http://dx.doi.org/10.1074/jbc.M113.525790
124. Toleman, C., A.J. Paterson, T.R. Whisenhunt, and J.E. Kudlow. 2004. Characterization of the histone acetyltransferase (HAT) domain of a bifunctional protein with activable O-GlcNAcase and HAT activities. J. Biol. Chem. 279:53665-53673. http://dx.doi.org/10.1074/jbc.M410406200
125. Trinidad, J.C., D.T. Barkan, B.F. Gulledge, A. Thalhammer, A. Sali, R. Schoepfer, and A.L. Burlingame. 2012. Global identification and characterization of both O-GlcNAcylation and phosphorylation at the murine synapse. Mol. Cell. Proteomics. 11:215-229. http://dx.doi.org/10.1074/mcp.O112.018366
126. Wang, P., B.D. Lazarus, M.E. Forsythe, D.C. Love, M.W. Krause, and J.A. Hanover. 2012a. O-GlcNAc cycling mutants modulate proteotoxicity in Caenorhabditis elegans models of human neurodegenerative diseases. Proc. Natl. Acad. Sci. USA. 109:17669-17674. http://dx.doi.org/10.1073/pnas.1205748109
127. Wang, S., X. Huang, D. Sun, X. Xin, Q. Pan, S. Peng, Z. Liang, C. Luo, Y. Yang, H. Jiang, et al. 2012b. Extensive crosstalk between O-GlcNAcylation and phosphorylation regulates Akt signaling. PLoS ONE. 7:e37427. http://dx.doi.org/10.1371/journal.pone.0037427
128. Wang, Z., M. Gucek, and G.W. Hart. 2008. Cross-talk between GlcNAcylation and phosphorylation: site-specific phosphorylation dynamics in response to globally elevated O-GlcNAc. Proc. Natl. Acad. Sci. USA. 105:13793-13798. http://dx.doi.org/10.1073/pnas.0806216105
129. Watzele, G., and W. Tanner. 1989. Cloning of the glutamine:fructose-6-phosphate amidotransferase gene from yeast. Pheromonal regulation of its transcription. J. Biol. Chem. 264:8753-8758.
130. Wells, L., Y. Gao, J.A. Mahoney, K. Vosseller, C. Chen, A. Rosen, and G.W. Hart. 2002. Dynamic O-glycosylation of nuclear and cytosolic proteins: further characterization of the nucleocytoplasmic beta-N-acetylglucosaminidase, O-GlcNAcase. J. Biol. Chem. 277:1755-1761. http://dx.doi .org/10.1074/jbc.M109656200
131. Whisenhunt, T.R., X. Yang, D.B. Bowe, A.J. Paterson, B.A. Van Tine, and J.E. Kudlow. 2006. Disrupting the enzyme complex regulating O-GlcNAcylation blocks signaling and development. Glycobiology. 16:551-563. http://dx .doi.org/10.1093/glycob/cwj096
132. Xie, H., S. Vucetic, L.M. Iakoucheva, C.J. Oldfield, A.K. Dunker, Z. Obradovic, and V.N. Uversky. 2007a. Functional anthology of intrinsic disorder. 3. Ligands, post-translational modifications, and diseases associated with intrinsically disordered proteins. J. Proteome Res. 6:1917-1932. http://dx.doi.org/10.1021/pr060394e
133. Xie, H., S. Vucetic, L.M. Iakoucheva, C.J. Oldfield, A.K. Dunker, V.N. Uversky, and Z. Obradovic. 2007b. Functional anthology of intrinsic disorder. 1. Biological processes and functions of proteins with long disordered regions. J. Proteome Res. 6:1882-1898. http://dx.doi.org/10.1021/pr060392u
134. Yang, W.H., J.E. Kim, H.W. Nam, J.W. Ju, H.S. Kim, Y.S. Kim, and J.W. Cho. 2006. Modification of p53 with O-linked N-acetylglucosamine regulates p53 activity and stability. Nat. Cell Biol. 8:1074-1083. http://dx.doi.org/10.1038/ncb1470
135. Yang, X., F. Zhang, and J.E. Kudlow. 2002. Recruitment of O-GlcNAc transferase to promoters by corepressor mSin3A: coupling protein O-GlcNAcylation to transcriptional repression. Cell. 110:69-80. http://dx.doi.org/10.1016/S0092-8674(02)00810-3
136. Yang, X., P.P. Ongusaha, P.D. Miles, J.C. Havstad, F. Zhang, W.V. So, J.E. Kudlow, R.H. Michell, J.M. Olefsky, S.J. Field, and R.M. Evans. 2008. Phosphoinositide signalling links O-GlcNAc transferase to insulin resistance. Nature. 451:964-969. http://dx.doi.org/10.1038/nature06668
137. Yang, Y.R., H.J. Jang, S. Yoon, Y.H. Lee, D. Nam, I.S. Kim, H. Lee, H. Kim, J.H. Choi, B.H. Kang, et al. 2014. OGA heterozygosity suppresses intestinal tumorigenesis in Apc(min/+) mice. Oncogenesis. 3:e109. http://dx.doi.org/10.1038/oncsis.2014.24
138. Yi, W., P.M. Clark, D.E. Mason, M.C. Keenan, C. Hill, W.A. Goddard III, E.C. Peters, E.M. Driggers, and L.C. Hsieh-Wilson. 2012. Phosphofructokinase 1 glycosylation regulates cell growth and metabolism. Science. 337:975-980. http://dx.doi.org/10.1126/science.1222278
139. Zachara, N.E., N. O'Donnell, W.D. Cheung, J.J. Mercer, J.D. Marth, and G.W. Hart. 2004. Dynamic O-GlcNAc modification of nucleocytoplasmic proteins in response to stress. A survival response of mammalian cells. J. Biol. Chem. 279:30133-30142. http://dx.doi.org/10.1074/jbc.M403773200
140. Zhang, F., K. Su, X. Yang, D.B. Bowe, A.J. Paterson, and J.E. Kudlow. 2003. O-GlcNAc modification is an endogenous inhibitor of the proteasome. Cell. 115:715-725. http://dx.doi.org/10.1016/S0092-8674(03)00974-7
141. Zhang, F., Y. Hu, P. Huang, C.A. Toleman, A.J. Paterson, and J.E. Kudlow. 2007. Proteasome function is regulated by cyclic AMP-dependent protein kinase through phosphorylation of Rpt6. J. Biol. Chem. 282:22460-22471. http://dx.doi.org/10.1074/jbc.M702439200
142. Zhang, Q., X. Liu, W. Gao, P. Li, J. Hou, J. Li, and J. Wong. 2014. Differential regulation of the ten-eleven translocation (TET) family of dioxygenases by O-linked β-N-acetylglucosamine transferase (OGT). J. Biol. Chem. 289:5986-5996. http://dx.doi.org/10.1074/jbc.M113.524140