The potential role of O-GlcNAc modification in cancer epigenetics

• Autorzy: Forma E. , Jozwiak P. , Brys M. , Krzeslak A.
• Języki publikacji: EN

Abstrakty

EN

There is no doubt that cancer is not only a genetic disease but that it can also occur due to epigenetic abnormalities. Diet and environmental factors can alter the scope of epigenetic regulation. The results of recent studies suggest that O-GlcNAcylation, which involves the addition of N-acetylglucosamine on the serine or threonine residues of proteins, may play a key role in the regulation of the epigenome in response to the metabolic status of the cell. Two enzymes are responsible for cyclic O-GlcNAcylation: O-GlcNAc transferase (OGT), which catalyzes the addition of the GlcNAc moiety to target proteins; and O-GlcNAcase (OGA), which removes the sugar moiety from proteins. Aberrant expression of O-GlcNAc cycling enzymes, especially OGT, has been found in all studied human cancers. OGT can link the cellular metabolic state and the epigenetic status of cancer cells by interacting with and modifying many epigenetic factors, such as HCF-1, TET, mSin3A, HDAC, and BAP1. A growing body of evidence from animal model systems also suggests an important role for OGT in polycomb-dependent repression of genes activity. Moreover, O-GlcNAcylation may be a part of the histone code: O-GlcNAc residues are found on all core histones.

Słowa kluczowe

EN

human disease; genetic disease; modification; cancer; epigenetics; diet; environmental factor; N-acetylglucosamine

• Wydawca: -
• Czasopismo: Cellular and Molecular Biology Letters
• Rocznik: 2014
• Tom: 19
• Numer: 3
• Opis fizyczny: p.438-460,fig.,ref.

Twórcy

autor

Forma E.

• Department of Cytobiochemistry, Faculty of Biology and Environmental Protection, University of Lodz, Pomorska 141/143, 90-237 Lodz, Poland

autor

Jozwiak P.

• Department of Cytobiochemistry, Faculty of Biology and Environmental Protection, University of Lodz, Pomorska 141/143, 90-237 Lodz, Poland

autor

Brys M.

• Department of Cytobiochemistry, Faculty of Biology and Environmental Protection, University of Lodz, Pomorska 141/143, 90-237 Lodz, Poland

autor

Krzeslak A.

• Department of Cytobiochemistry, Faculty of Biology and Environmental Protection, University of Lodz, Pomorska 141/143, 90-237 Lodz, Poland

Bibliografia

• 1.Goldberg, A.D., Allis, C.D. and Bernstein, E. Epigenetics: A landscape takes shape. Cell 128 (2007) 635–638.
• 2. Ducasse, M. and Brown, M.A. Epigenetic aberrations and cancer. Mol. Cancer 5 (2006) 60.
• 3. Sharma, S., Kelly, T.K. and Jones, P.A. Epigenetics in cancer. Carcinogenesis 31 (2010) 27–36.
• 4. Ellis, L., Atadja, P.W. and Johnstone, R.W. Epigenetics in cancer: targeting chromatin modifications. Mol. Cancer Ther. 8 (2009) 1409–1420.
• 5. Lim, U. and Song, M.A. Dietary and lifestyle factors of DNA methylation. Methods Mol. Biol. 863 (2012) 359–376.
• 6. Herceg, Z. Epigenetics and cancer: towards an evaluation of the impact of environmental and dietary factors. Mutagenesis 22 (2007) 91–103.
• 7. Hardy, T.M. and Tollefsbol, T.O. Epigenetic diet: impact on the epigenome and cancer. Epigenomics 3 (2011) 503–518.
• 8. Jiménez-Chillarón, J.C., Díaz, R., Martínez, D., Pentinat, T., Ramón-Krauel, M., Ribó, S. and Plösch, T. The role of nutrition on epigenetic modifications and their implications on health. Biochimie 94 (2012) 2242–2263.
• 9. Roberts, D.L., Dive, C. and Renehan, A.G. Biological mechanisms linking obesity and cancer risk: new perspectives. Annu. Rev. Med. 61 (2010) 301–316.
• 10. Simon, D. and Balkau, B. Diabetes mellitus, hyperglycaemia and cancer. Diabetes Metab. 36 (2010) 182–191.
• 11. Bensinger, S.J. and Christofk, H.R. New aspects of the Warburg effect in cancer cell biology. Semin. Cell Dev. Biol. 23 (2012) 352–361.
• 12. Dang, C.V. Links between metabolism and cancer. Genes Dev. 26 (2012) 877–890.
• 13. Krzeslak, A., Wojcik-Krowiranda, K., Forma, E., Jozwiak, P., Romanowicz, H., Bienkiewicz, A. and Brys, M. Expression of GLUT1 and GLUT3 glucose transporters in endometrial and breast cancers. Pathol. Oncol. Res. 18 (2012) 721–728.
• 14. Jóźwiak, P., Krześlak, A., Pomorski, L. and Lipińska, A. Expression of hypoxia-related glucose transporters GLUT1 and GLUT3 in benign, malignant and non-neoplastic thyroid lesions. Mol. Med. Rep. 6 (2012) 601–606.
• 15. Jóźwiak, P. and Lipińska, A. The role of glucose transporter 1 (GLUT1) in the diagnosis and therapy of tumors. Post. Hig. Med. Dosw. 66 (2012) 165–174.
• 16. Szablewski, L. Expression of glucose transporters in cancers. Biochim. Biophys. Acta 1835, (2013) 164–169.
• 17. Butkinaree, C., Park, K. and Hart, G.W. O-linked beta-N-acetylglucosamine (O-GlcNAc): Extensive crosstalk with phosphorylation to regulate signaling and transcription in response to nutrients and stress. Biochim. Biophys. Acta 1800 (2010) 96–106.
• 18. Slawson, C., Copeland, R.J. and Hart, G.W. O-GlcNAc signaling: a metabolic link between diabetes and cancer? Trends Biochem. Sci. 35 (2010) 547–555.
• 19. Hanover, J.A., Krause, M.W. and Love, D.C. The hexosamine signaling pathway: O-GlcNAc cycling in feast or famine. Biochim. Biophys. Acta 1800 (2010) 80–95.
• 20. Slawson, C. and Hart, G.W. O-GlcNAc signalling: implications for cancer cell biology. Nat. Rev. Cancer 11 (2011) 678–684.
• 21. Vocadlo, D.J. O-GlcNAc processing enzymes: catalytic mechanisms, substrate specificity, and enzyme regulation. Curr. Opin. Chem. Biol. 16 (2012) 488–497.
• 22. Bullen, J.W., Balsbaugh, J.L., Chanda, D., Shabanowitz, J., Hunt, D.F., Neumann, D. and Hart, G.W. Cross-talk between two essential nutrientsensitive enzymes: O-GlcNAc transferase (OGT) and AMP-activated protein kinase (AMPK). J. Biol. Chem. 289 (2014) 10592–606. DOI: 10.1074/jbc.M113.523068.
• 23. Xu, Q., Yang, C., Du, Y., Chen, Y., Liu, H., Deng, M., Zhang, H., Zhang, L., Liu, T., Liu, Q., Wang, L., Lou, Z. and Pei, H. AMPK regulates histone H2B O-GlcNAcylation. Nucleic Acids Res. (2014) DOI: 10.1093/nar/gku236.
• 24. Hu, P., Shimoji, S. and Hart, G.W. Site-specific interplay between O-GlcNAcylation and phosphorylation in cellular regulation. FEBS Lett. 584 (2010) 2526–2538.
• 25. Özcan, S., Andrali, S.S. and Cantrell, J.E. Modulation of transcription factor function by O-GlcNAc modification. Biochim. Biophys. Acta 1799 (2010) 353–364.
• 26. Ruan, H.B., Singh, J.P., Li, M.D., Wu, J. and Yang, X. Cracking the O-GlcNAc code in metabolism. Trends Endocrinol. Metab. 24 (2013) 301–309.
• 27. Hart, G.W., Slawson, C., Ramirez-Correa, G. and Lagerlof, O. Cross talk between O-GlcNAcylation and phosphorylation: roles in signaling, transcription, and chronic disease. Annu. Rev. Biochem. 80 (2011) 825–858.
• 28. Onodera, Y., Nam, J.M. and Bissell, M.J. Increased sugar uptake promotes oncogenesis via EPAC/RAP1 and O-GlcNAc pathways. J. Clin. Invest. (2013) DOI: 10.1172/JCI63146.
• 29. Li, Z. and Yi, W. Regulation of cancer metabolism by O-GlcNAcylation. Glycoconj. J. (2013) DOI 10.1007/s10719-013-9515-5.
• 30. Mi, W., Gu, Y., Han, C., Liu, H., Fan, Q., Zhang, X., Cong, Q., and Yu, W. O-GlcNAcylation is a novel regulator of lung and colon cancer malignancy. Biochim. Biophys. Acta 1812 (2011) 514–519.
• 31. Lynch, T.P., Ferrer, C.M., Jackson, S.R., Shahriari, K.S., Vosseller, K. and Reginato, M.J. Crtical role of O-linked β-N-acetylglucosamine transferase in prostate cancer invasion, angiogenesis, and metastasis. J. Biol. Chem. 287 (2012) 11070–11081.
• 32. Caldwell, S.A., Jackson, S.R., Shahriari, K.S., Lynch, T.P., Sethi, G., Walker, S., Vosseller, K. and Reginato, M.J. Nutrient sensor O-GlcNAc transferase regulates breast cancer tumorigenesis through targeting of the oncogenic transcription factor FoxM1. Oncogene 29 (2010) 2831–2842.
• 33. Gu, Y., Mi, W., Ge, Y., Liu, H., Fan, Q., Han, C., Yang, J., Han, F., Lu, X. and Yu, W. GlcNAcylation plays an essential role in breast cancer metastasis. Cancer Res. 70 (2010) 6344–6351.
• 34. Yehezkel, G., Cohen, L., Kliger, A., Manor, E. and Khalaila, I. O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) in primary and metastatic colorectal cancer clones and effect of N-acetyl-β-D-glucosaminidase silencing on cell phenotype and transcriptome. J. Biol. Chem. 287 (2012) 28755–28769.
• 35. Phueaouan, T., Chaiyawat, P., Netsirisawan, P., Chokchaichamnankit, D., Punyarit, P., Srisomsap, C., Svasti, J. and Champattanachai, V. Aberrant O-GlcNAc-modified proteins expressed in primary colorectal cancer. Oncol. Rep. 30 (2013) 2929–2936.
• 36. Zhu, Q., Zhou, L., Yang, Z., Lai, M., Xie, H., Wu, L., Xing, C., Zhang, F. and Zheng, S. O-GlcNAcylation plays a role in tumor recurrence of hepatocellular carcinoma following liver transplantation. Med. Oncol. 29 (2012) 985–993.
• 37. Ma, Z. and Vosseller, K. O-GlcNAc in cancer biology. Amino Acids 45 (2013) 719–733.
• 38. Shi, Y., Tomic, J., Wen, F., Shaha, S., Bahlo, A., Harrison, R., Dennis, J.W., Williams, R., Gross, B.J. and Walker, S. Aberrant O-GlcNAcylation characterizes chronic lymphocytic leukemia. Leukemia 24 (2010) 1588–1598.
• 39. Krześlak, A., Forma, E., Bernaciak, M., Romanowicz, H. and Bryś, M. Gene expression of O-GlcNAc cycling enzymes in human breast cancers. Clin. Exp. Med. 12 (2012) 61–65.
• 40. Krześlak, A., Wójcik-Krowiranda, K., Forma, E., Bieńkiewicz, A., Bryś, M. Expression of genes encoding for enzymes associated with O-GlcNAcylation in endometrial carcinomas: clinicopathologic correlations. Ginekol. Pol. 83 (2012) 22–26.
• 41. Rozanski, W., Krześlak, A., Forma, E., Bryś, M., Blewniewski, M., Wozniak, P., and Lipinski, M. Prediction of bladder cancer based on urinary content of MGEA5 and OGT mRNA level. Clin. Lab. 58 (2012) 579–583.
• 42. Champattanachai, V., Netsirisawan, P., Chaiyawat, P., Phueaouan, T., Charoenwattanasatien, R., Chokchaichamnankit, D., Punyarit, P., Srisomsap, C. and Svasti, J. Proteomic analysis and abrogated expression of O-GlcNAcylated proteins associated with primary breast cancer. Proteomics 13 (2013) 2088–2099.
• 43. Fardini, Y., Dehennaut, V., Lefebvre, T. and Issad, T. O-GlcNAcylation: a new cancer hallmark? Front. Endocrinol. 4 (2013) 99.
• 44. Wang, Z., Udeshi, N.D., Slawson, C., Compton, P.D., Sakabe, K., Cheung, W.D., Shabanowitz, J., Hunt, D.F. and Hart, G.W. Extensive crosstalk between O-GlcNAcylation and phosphorylation regulates cytokinesis. Sci. Signal. 3 (2010) ra2. DOI: 10.1126/scisignal.2000526.
• 45. Krześlak, A., Jóźwiak, P. and Lipińska, A. Down-regulation of β-N-acetylD-glucosaminidase increases Akt1 activity in thyroid anaplastic cancer cells. Oncol. Rep. 26 (2011) 743–749.
• 46. Huang, X., Pan, Q., Sun, D., Chen, W., Shen, A., Huang, M., Ding, J. and Geng, M. O-GlcNAcylation of cofilin promotes breast cancer cell invasion. J. Biol. Chem. 288 (2013) 36418–36425.
• 47. Park, S.Y., Kim, H.S., Kim, N.H., Ji, S., Cha, S.Y., Kang, J.G., Ota, I., Shimada, K., Konishi, N. and Nam, H.W. Snail1 is stabilized by O-GlcNAc modification in hyperglycaemic condition. EMBO J. 29 (2010) 3787–3796.
• 48. Thiery, J.P., Acloque, H., Huang, R.Y. and Nieto, M.A. Epithelialmesenchymal transitions in development and disease. Cell 139 (2009) 871–890.
• 49. Zhu, W., Leber, B. and Andrews, D.W. Cytoplasmic O-glycosylation prevents cell surface transport of E-cadherin during apoptosis. EMBO J. 20 (2001) 5999–6007.
• 50. Jin, F.Z., Yu, C., Zhao, D.Z., Wu, M.J. and Yang, Z. A correlation between altered O-GlcNAcylation, migration and with changes in E-cadherin levels in ovarian cancer cells. Exp. Cell. Res. 319 (2013) 1482–1490.
• 51. Kanwal, R. and Gupta, S. Epigenetic modifications in cancer. Clin. Genet. 81 (2012) 303–311.
• 52. Hassler, M.R. and Egger, G. Epigenomics of cancer - emerging new concepts. Biochimie 94 (2012) 2219–2230.
• 53. Tsai, H.C. and Baylin S.B. Cancer epigenetics: linking basic biology to clinical medicine. Cell Res. 21 (2011) 502–517.
• 54. Sakabe, K., Wang, Z. and Hart, G.W. Beta-N-acetylglucosamine (O-GlcNAc) is part of the histone code. Proc. Natl. Acad. Sci. USA 107 (2010) 19915–19920.
• 55. Zhang, S., Roche, K., Nasheuer, H.P. and 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 (2011) 37483–37495.
• 56. Fujiki, R., Hashiba, W., Sekine, H., Yokoyama, A., Chikanishi, T., Ito, S., Imai, Y., Kim, J., He, H.H., Igarashi, K., Kanno, J., Ohtake, F., Kitagawa, H., Roeder, R.G., Brown, M. and Kato, S. GlcNAcylation of histone H2B facilitates its monoubiquitination. Nature 480 (2011) 557–560.
• 57. Fong, J.J., Nguyen, B.L., Bridger, R., Medrano, E.E., Wells, L., Pan, S. and Sifers RN. β-N-Acetylglucosamine (O-GlcNAc) is a novel regulator of mitosis-specific phosphorylations on histone H3. J. Biol. Chem. 287 (2012) 12195–12203.
• 58. Gao, Z. and Xu, C.W. Glucose metabolism induces mono-ubiquitination of histone H2B in mammalian cells. Biochem. Biophys. Res. Commun. 404 (2011) 428–433.
• 59. Urasaki, Y., Heath, L. and Xu, C.W. Coupling of glucose deprivation with impaired histone H2B monoubiquitination in tumors. PLoS One 7 (2012) e36775.
• 60. Shema, E., Tirosh, I., Aylon, Y., Huang, J., Ye, C., Moskovits, N., RaverShapira, N., Minsky, N., Pirngruber, J., Tarcic, G., Hublarova, P., Moyal, L., Gana-Weisz, M., Shiloh, Y., Yarden, Y., Johnsen, S.A., Vojtesek, B., Berger, S.L. and Oren M. The histone H2B-specific ubiquitin ligase RNF20/hBRE1 acts as a putative tumor suppressor through selective regulation of gene expression. Genes Dev. 22 (2008) 2664–2676.
• 61. Chernikova, S.B., Razorenova, O.V., Higgins, J.P., Sishc, B.J., Nicolau, M., Dorth, J.A., Chernikova, D.A., Kwok, S., Brooks, J.D., Bailey, S.M., Game, J.C. and Brown J.M. Deficiency in mammalian histone H2B ubiquitin ligase Bre1 (Rnf20/Rnf40) leads to replication stress and chromosomal instability. Cancer Res. 72 (2012) 2111–2119.
• 62. Chen, Q., Chen, Y., Bian, C., Fujiki, R. and Yu, X. TET2 promotes histone O-GlcNAcylation during gene transcription. Nature 493 (2013) 561–564.
• 63. Deplus, R., Delatte, B., Schwinn, M.K., Defrance, M., Méndez, J., Murphy, N., Dawson, M.A., Volkmar, M., Putmans, P., Calonne, E., Shih, A.H., Levine, R.L., Bernard, O., Mercher, T., Solary, E., Urh, M., Daniels, D.L. and Fuks, F. TET2 and TET3 regulate GlcNAcylation and H3K4 methylation through OGT and SET1/COMPASS. EMBO J. 32 (2013) 645–655.
• 64. Sakabe, K. and Hart, G.W. O-GlcNAc transferase regulates mitotic chromatin dynamics. J. Biol. Chem. 285 (2010) 34460–34468.
• 65. Baek, S.H. When signaling kinases meet histones and histone modifiers in the nucleus. Mol. Cell 42 (2011) 274–284.
• 66. Nowak, S.J. and Corces, V.G. Phosphorylation of histone H3: a balancing act between chromosome condensation and transcriptional activation. Trends Genet. 20 (2004) 214–220.
• 67. Choi, H.S., Choi, B.Y., Cho, Y.Y., Mizuno, H., Kang, B.S.,. Bode, A.M. and Dong, Z. Phosphorylation of histone H3 at serine 10 is indispensable for neoplastic cell transformation. Cancer Res. 65 (2005) 5818–5827.
• 68. Zippo, A., De Robertis, A., Serafini, R. and Oliviero, S. PIM1-dependent phosphorylation of histone H3 at serine 10 is required for MYC-dependent transcriptional activation and oncogenic transformation. Nat. Cell. Biol. 9 (2007) 932–944.
• 69. Chadee, D.N., Hendzel, M.J., Tylipski, C.P., Allis, C.D., Bazett-Jones, D.P., Wright, J.A. and Davie, J.R. Increased Ser-10 phosphorylation of histone H3 in mitogen stimulated and oncogene-transformed mouse fibroblasts. J. Biol. Chem. 274 (1999) 24914–24920.
• 70. Strelkov, I.S. and Davie, J.R. Ser-10 phosphorylation of histone H3 and immediate early gene expression in oncogene-transformed mouse fibroblasts. Cancer Res. 62 (2002) 75–78.
• 71. Kim, H.G., Lee, K.W., Cho, Y.Y., Kang, N.J., Oh, S.M., Bode, A.M. and Dong, Z. Mitogen and stress-activated kinase 1-mediated histone H3 phosphorylation is crucial for cell transformation. Cancer Res. 68 (2008) 2538–2547.
• 72. Tange, S., Ito, S., Senga, T. and Hamaguchi, M. Phosphorylation of histone H3 at Ser10: its role in cell transformation by v-Src. Biochem. Biophys. Res. Commun. 386 (2009) 588–592.
• 73. Portella, G., Passaro, C. and Chieffi, P. Aurora B: a new prognostic marker and therapeutic target in cancer. Curr. Med. Chem. 18 (2011) 482–496.
• 74. Murnion, M.E., Adams, R.R., Callister, D.M., Allis, C.D., Earnshaw, W.C. and Swedlow, J.R. Chromatin-associated protein phosphatase 1 regulates aurora-B and histone H3 phosphorylation. J. Biol. Chem. 276 (2001) 26656–26665.
• 75. Wells, L., Kreppel, L.K., Comer, F.I., Wadzinski, B.E. and Hart, G.W. O-GlcNAc transferase is in a functional complex with protein phosphatase 1 catalytic subunits. J. Biol. Chem. 279 (2004) 38466–38470.
• 76. Slawson, C., Lakshmanan, T., Knapp, S., Hart, G.W. A mitotic GlcNAcylation/phosphorylation signaling complex alters the posttranslational state of the cytoskeletal protein vimentin. Mol. Biol. Cell 19 (2008) 4130–4140.
• 77. Tan, E.P., Caro, S., Potnis, A., Lanza, C. and Slawson, C. O-linked N-acetylglucosamine cycling regulates mitotic spindle organization. J. Biol. Chem. 288 (2013) 27085–27099.
• 78. Capotosti, F., Guernier, S., Lammers, F., Waridel, P., Cai, Y., Jin, J., Conaway, J.W., Conaway, R.C. and Herr, W. O-GlcNAc transferase catalyzes site-specific proteolysis of HCF-1. Cell 144 (2011) 376–388.
• 79. Hanover, JA. A versatile sugar transferase makes the cut. Cell 144 (2011) 321–322.
• 80. Coller, H.A. Is cancer a metabolic disease? Am. J. Pathol. 184 (2014) 4–17.
• 81. Ruan, H.B., Han, X., Li, M.D., Singh, J.P., Qian, K., Azarhoush, S., Zhao, L., Bennett, A.M., Samuel, V.T., Wu, J., Yates, J.R. 3rd and Yang, X. O-GlcNAc transferase/host cell factor C1 complex regulates gluconeogenesis by modulating PGC-1α stability. Cell Metab. 16 (2012) 226–237. DOI: 10.1016/j.cmet.2012.07.006.
• 82. Zargar, Z.U. and Tyagi, S. Role of host cell factor-1 in cell cycle regulation. Transcription 34 (2012) 187–192.
• 83. Glinsky, G.V., Berezovska, O. and Glinskii, A.B. Microarray analysis identifies a death-from-cancer signature predicting therapy failure in patients with multiple types of cancer. J. Clin. Invest. 115 (2005) 1503–1521.
• 84. Julien, E. and Herr, W. Proteolytic processing is necessary to separate an ensure proper cell growth and cytokinesis functions of HCF-1. EMBO J. 22 (2003) 2360–2369.
• 85. Julien, E. and Herr, W. A switch in mitotic histone H4 lysine 20 methylation status is linked to M phase defects upon loss of HCF1. Mol. Cell 14 (2004) 713–725.
• 86. Tyagi, S. and Herr, W. E2F mediates DNA damage and apoptosis through HCF-1 and the MLL family of histone methyltransferase. EMBO J. 28 (2009) 3185–3195.
• 87. Wysocka, J., Myers, M.P., Laherty, C.D., Eisenman, R.N. and Herr, W. Human Sin3 deacetylase and trithorax-related Set1/Ash2 histone H3-K4 methyltransferase are tethered together selectively by the cell-proliferation factor HCF-1. Genes Dev. 17 (2003) 896–911.
• 88. Mazars, R., Gonzalez-de-Peredo, A., Cayrol, C., Lavigne, A.C., Vogel, J.L., Ortega, N., Lacroix, C., Gautier, V., Huet, G., Ray, A., Monsarrat, B., Kristie, T.M. and Girard, J.P. The THAP-zinc finger protein THAP1 associates with coactivator HCF-1 and O-GlcNAc transferase: a link between DYT6 and DYT3 dystonias. J. Biol. Chem. 285 (2010) 13364–13371.
• 89. Daou, S., Mashtalir, N., Hammond-Martel, I., Pak, H., Yu, H., Sui, G., Vogel, J.L., Kristie, T.M. and Affar el, B. Crosstalk between OGlcNAcylation and proteolytic cleavage regulates the host cell factor-1 maturation pathway. Proc. Natl. Acad. Sci. USA 108 (2011) 2747–2752.
• 90. Lazarus, M.B., Jiang, J., Kapuria, V., Bhuiyan, T., Janetzko, J., Zandberg, W.F., Vocadlo, D.J., Herr, W. and Walker, S. HCF-1 is cleaved in the active site of O-GlcNAc transferase. Science 342 (2013) 1235–1239.
• 91. Reilly, P.T., Wysocka, J. and Herr, W. Inactivation of the retinoblastoma protein family can bypass the HCF-1 defect in tsBN67 cell proliferation and cytokinesis. Mol. Cell. Biol. 22 (2002) 6767–6778.
• 92. Wells, L., Slawson, C. and Hart, G.W. The E2F-1 associated retinoblastomasusceptibility gene product is modified by O-GlcNAc. Amino Acids 40 (2011) 877–883.
• 93. Murali, R., Wiesner, T. and Scolyer, R.A. Tumors associated with BAP1 mutations. Pathology 45 (2013) 116–126.
• 94. Dey, A., Seshasayee, D., Noubade, R., French, D.M., Liu, J., Chaurushiya, M.S., Kirkpatrick, D.S., Pham, V.C., Lill, J.R., Bakalarski, C.E., Wu, J., Phu, L., Katavolos, P., LaFave, L.M., Abdel-Wahab, O., Modrusan, Z., Seshagiri, S., Dong, K,. Lin, Z., Balazs, M., Suriben, R., Newton, K., Hymowitz, S., Garcia-Manero, G., Martin, F., Levine, R.L. and Dixit V. M. Loss of the tumor suppressor BAP1 causes myeloid transformation. Science 337 (2012) 1541–1546.
• 95. Yang, X., Zhang, F. and Kudlow, J.E. Recruitment of O-GlcNAc transferase to promoters by corepressor mSin3A: coupling protein O-GlcNAcylation to transcriptional repression. Cell 110 (2002) 69–80.
• 96. Cayrol, C., Lacroix, C., Mathe, C., Ecochard, V., Ceribelli, M., Loreau, E., Lazar, V., Dessen, P., Mantovani, R., Aguilar, L. and Girard, J.P. The THAP-zinc finger protein THAP1 regulates endothelial cell proliferation through modulation of pRB/E2F cell-cycle target genes. Blood 109 (2007) 584–594.
• 97. Macfarlan, T., Kutney, S., Altman, B., Montross, R., Yu, J., Chakravarti, D. and Girard, J.P. Human THAP7 is a chromatin-associated, histone tail-binding protein that represses transcription via recruitment of HDAC3 and nuclear hormone receptor corepressor. J. Biol. Chem. 280 (2005) 7346–7358.
• 98. Roussigne, M., Cayrol, C., Clouaire, T., Amalric, F. and Girard, J.P. THAP1 is a nuclear proapoptotic factor that links prostate-apoptosis-response-4 (Par-4) to PML nuclear bodies. Oncogene 22 (2003) 2432–2442.
• 99. Zhu, C.Y., Li, C.Y., Li, Y., Zhan, Y.Q., Li, Y.H., Xu, C.W., Xu, W.X., Sun, H.B. and Yang, X.M. Cell growth suppression by thanatos-associated protein 11 (THAP11) is mediated by transcriptional downregulation of c-Myc. Cell Death Differ. 16 (2009) 395–405.
• 100. Dejosez, M., Krumenacker, J.S., Zitur, L.J., Passeri, M., Chu, L.F., Songyang, Z., Thomson, J.A. and Zwaka, T.P. Ronin is essential for embryogenesis and the pluripotency of mouse embryonic stem cells. Cell 133 (2008) 1162–1174.
• 101. Parker, J.B., Palchaudhuri, S., Yin, H., Wei, J. and Chakravarti, D.A. Transcriptional regulatory role of the THAP11-HCF-1 complex in colon cancer cell function. Mol. Cell. Biol. 32 (2012) 1654–1670.
• 102. Ito, S., D'Alessio, A.C., Taranova, O.V., Hong, K., Sowers, L.C. and Zhang, Y. Role of Tet proteins in 5mC to 5hmC conversion, ES-cell self-renewal and inner cell mass specification. Nature 466 (2010) 1129–1133.
• 103. Tahiliani, M., Koh, K.P., Shen, Y., Pastor, W.A., Bandukwala, H., Brudno, Y., Agarwal, S., Iyer, L.M., Liu, D.R., Aravind, L. and Rao, A. Conversion of 5-methylcytosine to 5-hydroxymethylcytosine in mammalian DNA by MLL partner TET1. Science 324 (2009) 930–935.
• 104. Kriaucionis, S. and Heintz, N. The nuclear DNA base 5-hydroxymethylcytosine is present in Purkinje neurons and the brain. Science 324 (2009) 929–930.
• 105. Pfeifer, G.P., Kadam, S. and Jin, S.G. 5-hydroxymethylcytosine and its potential roles in development and cancer. Epigenetics Chromatin. 6 (2013) 10.
• 106. Lorsbach, R.B., Moore, J., Mathew, S., Raimondi, S.C., Mukatira, S.T. and Downing, J.R. TET1, a member of a novel protein family, is fused to MLL in acute myeloid leukemia containing the t(10;11)(q22;q23). Leukemia 17 (2003) 637–641.
• 107. Delatte, B. and Fuks, F. TET proteins: on the frenetic hunt for new cytosine modifications. Brief Funct. Genomics 12 (2013) 191–204.
• 108. Tan, L. and Shi, Y.G. Tet family proteins and 5-hydroxymethylcytosine in development and disease. Development 139 (2012) 1895–1902.
• 109. Jin, S.G, Jiang, Y., Qiu, R., Rauch, T.A., Wang, Y., Schackert, G., Krex, D., Lu, Q. and Pfeifer, G.P. 5-Hydroxymethylcytosine is strongly depleted in human cancers but its levels do not correlate with IDH1 mutation. Cancer Res. 71 (2011) 7360–7365.
• 110. Haffner, M.C., Chaux, A., Meeker, A.K., Esopi, D.M., Gerber, J., Pellakuru, L.G., Toubaji, A., Argani, P., Iacobuzio-Donahue, C., Nelson, W.G., Netto, G.J., De Marzo, A.M. and Yegnasubramanian, S. Global 5-hydroxymethylcytosine content is significantly reduced in tissue stem/progenitor cell compartments and in human cancers. Oncotarget 6 (2011) 627–637.
• 111. Yang, H., Liu, Y., Bai, F., Zhang, J.Y., Ma, S.H., Liu, J., Xu, Z.D., Zhu, H.G., Ling, Z.Q., Ye, D., Guan, K.L. and Xiong, Y. Tumor development is associated with decrease of TET gene expression and 5-methylcytosine hydroxylation. Oncogene 6 (2013) 663–669.
• 112. Kraus, T.F., Globisch, D., Wagner, M., Eigenbrod, S., Widmann, D., Munzel, M., Muller, M., Pfaffeneder, T., Hackner, B., Feiden, W., Schüller, U., Carell, T. and Kretzschmar, H.A. Low values of 5-hydroxymethylcytosine (5hmC), the “sixth base”, are associated with anaplasia in human brain tumors. Int. J. Cancer 6 (2012) 1577–1590.
• 113. Kudo, Y., Tateishi, K., Yamamoto, K., Yamamoto, S., Asaoka, Y., Ijichi, H., Nagae, G., Yoshida, H., Aburatani, H. and Koike, K. Loss of 5-hydroxymethylcytosine is accompanied with malignant cellular transformation. Cancer Sci. 6 (2012) 670–676.
• 114. Lian, C.G., Xu, Y., Ceol, C., Wu, F., Larson, A., Dresser, K., Xu, W., Tan, L., Hu, Y., Zhan, Q., Lee, C.W., Hu, D., Lian, B.Q., Kleffel, S., Yang, Y., Neiswender, J., Khorasani, A.J., Fang, R., Lezcano, C., Duncan, L.M., Scolyer, R.A., Thompson, J.F., Kakavand, H., Houvras, Y., Zon, L.I., Mihm, M.C. Jr, Kaiser, U.B., Schatton, T., Woda, B.A., Murphy, G.F., Shi, Y.G. Loss of 5-hydroxymethylcytosine is an epigenetic hallmark of melanoma. Cell 6 (2012) 1135–1146.
• 115. Ito, R., Katsura, S., Shimada, H., Tsuchiya, H., Hada, M., Okumura, T., Sugawara, A. and Yokoyama, A. TET3-OGT interaction increases the stability and the presence of OGT in chromatin. Genes Cells 19 (2014) 52–65.
• 116. Wu, H., D'Alessio, A.C., Ito, S., Xia, K., Wang, Z., Cui, K., Zhao, K., Sun, Y.E. and Zhang, Y. Dual functions of Tet1 in transcriptional regulation in mouse embryonic stem cells. Nature 473 (2011) 389–393.
• 117. Williams, K., Christensen, J., Pedersen, M.T., Johansen, J.V., Cloos, P.A., Rappsilber, J. and Helin, K. TET1 and hydroxymethylcytosine in transcription and DNA methylation fidelity. Nature 473 (2011) 343–348.
• 118. Shi, F.T., Kim, H., Lu, W., He, Q., Liu, D., Goodell, M.A., Wan, M. and Songyang, Z. Ten-eleven translocation 1 (Tet1) is regulated by O-linked N-acetylglucosamine transferase (Ogt) for target gene repression in mouse embryonic stem cells. J. Biol. Chem. 288 (2013) 20776–20784.
• 119. Yang, Q., Wu, K., Ji, M., Jin, W., He, N., Shi, B. and Hou, P. Decreased 5-hydroxymethylcytosine (5-hmC) is an independent poor prognostic factor in gastric cancer patients. J. Biomed. Nanotechnol. 9 (2013) 1607–1616.
• 120. Fu, H.L., Ma, Y., Lu, L.G., Hou, P., Li, B.J., Jin, W.L. and Cui, D.X. TET1 exerts its tumor suppressor function by interacting with p53-EZH2 pathway in gastric cancer J. Biomed. Nanotechnol. 10 (2014) 1217–1230.
• 121. Hsu, C.H., Peng, K.L., Kang, M.L., Chen, Y.R., Yang, Y.C., Tsai, C.H., Chu, C.S., Jeng, Y.M., Chen, Y.T., Lin, F.M., Huang, H.D., Lu, Y.Y., Teng, Y.C., Lin, S.T., Lin, R.K., Tang, F.M., Lee, S.B., Hsu, H.M., Yu, J.C., Hsiao, P.W and Juan, L.J. TET1 suppresses cancer invasion by activating the tissue inhibitors of metalloproteinases. Cell Rep. 2 (2012) 568–579. DOI: 10.1016/j.celrep.2012.08.030.
• 122. Gambetta, M.C., Oktaba, K. and Müller, J. Essential role of the glycosyltransferase sxc/Ogt in polycomb repression. Science 325 (2009) 93–96.
• 123. Sinclair, D.A., Syrzycka, M., Macauley, M.S., Rastgardani, T., Komljenovic, I., Vocadlo, D.J., Brock, H.W. and Honda, B.M. Drosophila O-GlcNAc transferase (OGT) is encoded by the Polycomb group (PcG) gene, super sex combs (sxc). Proc. Natl. Acad. Sci. USA 106 (2009) 13427–13432.
• 124. Love, D.C., Krause, M.W. and Hanover, J.A. O-GlcNAc cycling: emerging roles in development and epigenetics. Semin. Cell. Dev. Biol. 21 (2010) 646–654.
• 125. Hanover, J.A., Krause, M.W. and Love, D.C. Bittersweet memories: linking metabolism to epigenetics through O-GlcNAcylation. Nat. Rev. Mol. Cell. Biol. 13 (2012) 312–321.
• 126. Leeb, M. and Wutz, A. Establishment of epigenetic patterns in development. Chromosoma 121 (2012) 251–262.
• 127. Richly, H., Aloia, L. and Di Croce, L. Roles of the Polycomb group proteins in stem cells and cancer. Cell. Death Dis. 2 (2011) e204.
• 128. Morey, L. and Helin, K. Polycomb group protein-mediated repression of transcription. Trends Biochem. Sci. 35 (2010) 323–332.
• 129. Kuzmichev, A., Nishioka, K., Erdjument-Bromage, H., Tempst, P. and Reinberg, D. Histone methyltransferase activity associated with a human multiprotein complex containing the Enhancer of Zeste protein. Genes Dev. 16 (2002) 2893–2905.
• 130. Francis, N.J., Kingston, R.E. and Woodcock, C.L. Chromatin compaction by a polycomb group protein complex. Science 306 (2004) 1574–1577.
• 131. Tsang, D.P. and Cheng, A.S. Epigenetic regulation of signaling pathways in cancer: role of the histone methyltransferase EZH2. J. Gastroenterol. Hepatol. 26 (2011) 19–27.
• 132. Myers, S.A., Panning, B. and 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 (2011) 9490–9495.
• 133. Chu, C.S., Lo, P.W., Yeh, Y.H., Hsu, P.H., Peng, S.H., Teng, Y.C., Kang, M.L., Wong, C.H. and Juan, L.J. O-GlcNAcylation regulates EZH2 protein stability and function. Proc. Natl. Acad. Sci. USA. 111 (2014) 1355–1360. DOI: 10.1073/pnas.1323226111.