O-GlcNAcylation and cardiovascular disease

Biochemical Society Transactions

Volumn 45, Issue 2, 2017, Pages 545-553

  Wright, JaLessa N ^a   Collins, Helen E ^a   Wende, Adam R ^a   Chatham, John C ^a  

^a University of Alabama at Birmingham   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CARDIOVASCULAR DISEASE; CARDIOVASCULAR FUNCTION; CELL METABOLISM; DIABETES MELLITUS; HEART FAILURE; HEART HYPERTROPHY; HUMAN; MYOCARDIAL ISCHEMIA REPERFUSION INJURY; O GLCNACYLATION; PRIORITY JOURNAL; REVIEW; ANIMAL; CHEMISTRY; GENE EXPRESSION REGULATION; GLYCOSYLATION; METABOLISM; PROTEIN PROCESSING; SIGNAL TRANSDUCTION;

N ACETYLGLUCOSAMINE; PROTEIN;

ACETYLGLUCOSAMINE; ANIMALS; CARDIOVASCULAR DISEASES; DIABETES MELLITUS; GENE EXPRESSION REGULATION; GLYCOSYLATION; HUMANS; PROTEIN PROCESSING, POST-TRANSLATIONAL; PROTEINS; SIGNAL TRANSDUCTION;

EID: 85018465104     PISSN: 03005127     EISSN: 14708752     Source Type: Journal    
DOI: 10.1042/BST20160164     Document Type: Review

References (72)

1. Roquemore, E.P., Chevrier, M.R., Cotter, R.J. and Hart, G.W. (1996) Dynamic O-GlcNAcylation of the small heat shock protein αB-crystallin. Biochemistry 35, 3578-3586 doi:10.1021/bi951918j
2. Yki-Järvinen, H., Vogt, C., Iozzo, P., Pipek, R., Daniels, M.C., Virkamäki, A. et al. (1997) UDP-N-acetylglucosamine transferase and glutamine: fructose 6-phosphate amidotransferase activities in insulin-sensitive tissues. Diabetologia 40, 76-81 doi:10.1007/s001250050645
3. Han, I. and Kudlow, J.E. (1997) Reduced O-glycosylation of Sp1 is associated with increased proteasome susceptibility. Mol. Cell. Biol. 17, 2550-2558 doi:10.1128/MCB.17.5.2550
4. Wende, A.R. (2016) Post-translational modifications of the cardiac proteome in diabetes and heart failure. Proteomics Clin. Appl. 10, 25-38 doi:10.1002/prca.201500052
5. Dassanayaka, S. and Jones, S.P. (2014) O-GlcNAc and the cardiovascular system. Pharmacol. Ther. 142, 62-71 doi:10.1016/j.pharmthera.2013.11.005
6. Marsh, S.A., Collins, H.E. and Chatham, J.C. (2014) Protein O-GlcNAcylation and cardiovascular (patho)physiology. J. Biol. Chem. 289, 34449-34456 doi:10.1074/jbc.R114.585984
7. Mailleux, F., Gélinas, R., Beauloye, C., Horman, S. and Bertrand, L. (2016) O-GlcNAcylation, enemy or ally during cardiac hypertrophy development? Biochim. Biophys. Acta, Mol. Basis Dis. 1862, 2232-2243; in press
8. Banerjee, P.S., Lagerlöf, O. and Hart, G.W. (2016) Roles of O-GlcNAc in chronic diseases of aging. Mol. Aspects Med. 51, 1-15 doi:10.1016/j.mam.2016.05.005
9. McLarty, J.L., Marsh, S.A. and Chatham, J.C. (2013) Post-translational protein modification by O-linked N-acetyl-glucosamine: its role in mediating the adverse effects of diabetes on the heart. Life Sci. 92, 621-627 doi:10.1016/j.lfs.2012.08.006
10. Chatham, J.C. and Marchase, R.B. (2010) The role of protein O-linked β-N-acetylglucosamine in mediating cardiac stress responses. Biochim. Biophys. Acta, Gen. Subj. 1800, 57-66 doi:10.1016/j.bbagen.2009.07.004
11. Laczy, B., Marsh, S.A., Brocks, C.A., Wittmann, I. and Chatham J.C. (2010) Inhibition of O-GlcNAcase in perfused rat hearts by NAG-thiazolines at the time of reperfusion is cardioprotective in an O-GlcNAc-dependent manner. Am. J. Physiol. Heart Circ. Physiol. 299, H1715-H1727 doi:10.1152/ajpheart.00337.2010
12. Jin, P.-Y., Zhang, H.-S., Guo, X.-Y., Liang, W.-F. and Han, Q.-F. (2014) Glucose-insulin-potassium therapy in patients with acute coronary syndrome: a meta-analysis of randomized controlled trials. BMC Cardiovasc. Disord. 14, 169 doi:10.1186/1471-2261-14-169
13. Zhao, Y.-T., Weng, C.-L., Chen, M.-L., Li, K.-B., Ge, Y.-G., Lin, X.-M. et al. (2010) Comparison of glucose-insulin-potassium and insulin-glucose as adjunctive therapy in acute myocardial infarction: a contemporary meta-analysis of randomised controlled trials. Heart 96, 1622-1626 doi:10.1136/hrt.2010.194563
14. Straus, S., Gerc, V., Kacila, M. and Custovic, F. (2013) Glucosa-insulin-potassium (GIK) solution used with diabetic patients provides better recovery after coronary bypass operations. Med. Arh. 67, 84-87 doi:10.5455/medarh.2013.67.84-87
15. Shim, J.-K., Yang, S.-Y., Yoo, Y.-C., Yoo, K.-J. and Kwak, Y.-L. (2013) Myocardial protection by glucose-insulin-potassium in acute coronary syndrome patients undergoing urgent multivessel off-pump coronary artery bypass surgery. Br. J. Anaesth. 110, 47-53 doi:10.1093/bja/aes324
16. Champattanachai, V., Marchase, R.B. and Chatham, J.C. (2007) Increased flux through the hexosamine biosynthesis pathway protects cardiomyocytes from ischemia-reperfusion injury. Am. J. Physiol. - Cell Physiol. 292, C178-C187 doi:10.1152/ajpcell.00162.2006
17. Chun, W.-J., Nah, D.-Y., Bae, J.-H., Chung, J.-W., Lee, H. and Moon, I.S. (2015) Glucose-insulin-potassium solution protects ventricular myocytes of neonatal rat in an in vitro coverslip ischemia/reperfusion model. Korean Circ. J. 45, 234-241 doi:10.4070/kcj.2015.45.3.234
18. Howell, N.J., Ashrafian, H., Drury, N.E., Ranasinghe, A.M., Contractor, H., Isackson, H. et al. (2011) Glucose-insulin-potassium reduces the incidence of low cardiac output episodes after aortic valve replacement for aortic stenosis in patients with left ventricular hypertrophy: results from the hypertrophy, insulin, glucose, and electrolytes (HINGE) trial. Circulation 123, 170-177 doi:10.1161/CIRCULATIONAHA.110.945170
19. Taegtmeyer, H. and Khalaf, K.I. (2011) Letter by Taegtmeyer and Khalaf regarding article, "Glucose-insulin-potassium reduces the incidence of low cardiac output episodes after aortic valve replacement for aortic stenosis in patients with left ventricular hypertrophy: results from the hypertrophy, insulin, glucose, and electrolytes (HINGE) trial". Circulation 124, e385 doi:10.1161/CIRCULATIONAHA.111.028795
20. Yu, Q., Zhou, N., Nan, Y., Zhang, L., Li, Y., Hao, X. et al. (2014) Effective glycaemic control critically determines insulin cardioprotection against ischaemia/reperfusion injury in anaesthetized dogs. Cardiovasc. Res. 103, 238-247 doi:10.1093/cvr/cvu132
21. Vibjerg Jensen, R., Johnsen, J., Kristiansen, S.B., Zachara, N.E. and Bøtker, H.E. (2013) Ischemic preconditioning increases myocardial O-GlcNAc glycosylation. Scand. Cardiovasc. J. 47, 168-174 doi:10.3109/14017431.2012.756984
22. Ngoh, G.A., Watson, L.J., Facundo, H.T. and Jones, S.P. (2011) Augmented O-GlcNAc signaling attenuates oxidative stress and calcium overload in cardiomyocytes. Amino Acids 40, 895-911 doi:10.1007/s00726-010-0728-7
23. Champattanachai, V., Marchase, R.B. and Chatham, J.C. (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-C1520 doi:10.1152/ajpcell.00456.2007
24. Liu, J., Marchase, R.B. and Chatham, J.C. (2007) Increased O-GlcNAc levels during reperfusion lead to improved functional recovery and reduced calpain proteolysis. Am. J. Physiol. Heart Circ. Physiol. 293, H1391-H1399 doi:10.1152/ajpheart.00285.2007
25. Liu, J., Pang, Y., Chang, T., Bounelis, P., Chatham, J. and Marchase, R. (2006) Increased hexosamine biosynthesis and protein O-GlcNAc levels associated with myocardial protection against calcium paradox and ischemia. J. Mol. Cell Cardiol. 40, 303-312 doi:10.1016/j.yjmcc.2005.11.003
26. Jones, S.P., Zachara, N.E., Ngoh, G.A., Hill, B.G., Teshima, Y., Bhatnagar, A. et al. (2008) Cardioprotection by N-acetylglucosamine linkage to cellular proteins. Circulation 117, 1172-1182 doi:10.1161/CIRCULATIONAHA.107.730515
27. Groves, J.A., Lee, A., Yildirir, G. and Zachara, N.E. (2013) Dynamic O-GlcNAcylation and its roles in the cellular stress response and homeostasis. Cell Stress Chaperones 18, 535-558 doi:10.1007/s12192-013-0426-y
28. Lee, H.J., Ryu, J.M., Jung, Y.H., Lee, K.H., Kim, D.I. and Han, H.J. (2016) Glycerol-3-phosphate acyltransferase-1 upregulation by O-GlcNAcylation of Sp1 protects against hypoxia-induced mouse embryonic stem cell apoptosis via mTOR activation. Cell Death Dis. 7, e2158 doi:10.1038/cddis.2015.410
29. Lunde, I.G., Aronsen, J.M., Kvaloy, H., Qvigstad, E., Sjaastad, I., Tonnessen, T. et al. (2012) Cardiac O-GlcNAc signaling is increased in hypertrophy and heart failure. Physiol. Genomics 44, 162-172 doi:10.1152/physiolgenomics.00016.2011
30. Marsh, S.A., Dell'Italia, L.J. and Chatham, J.C. (2011) Activation of the hexosamine biosynthesis pathway and protein O-GlcNAcylation modulate hypertrophic and cell signaling pathways in cardiomyocytes from diabetic mice. Amino Acids 40, 819-828 doi:10.1007/s00726-010-0699-8
31. Facundo, H.T., Brainard, R.E., Watson, L.J., Ngoh, G.A., Hamid, T., Prabhu, S.D. et al. (2012) O-GlcNAc signaling is essential for NFAT-mediated transcriptional reprogramming during cardiomyocyte hypertrophy. Am. J. Physiol. Heart Circ. Physiol. 302, H2122-H2130 doi:10.1152/ajpheart.00775.2011
32. Olson, A.K., Ledee, D., Iwamoto, K., Kajimoto, M., O'Kelly Priddy, C., Isern, N. et al. (2013) C-Myc induced compensated cardiac hypertrophy increases free fatty acid utilization for the citric acid cycle. J. Mol. Cell Cardiol. 55, 156-164 doi:10.1016/j.yjmcc.2012.07.005
33. Ledee, D., Smith, L., Bruce, M., Kajimoto, M., Isern, N., Portman, M.A. et al. (2015) c-Myc alters substrate utilization and O-GlcNAc protein posttranslational modifications without altering cardiac function during early aortic constriction. PLoS ONE 10, e0135262 doi:10.1371/journal.pone.0135262
34. Guo, X., Shang, J., Deng, Y., Yuan, X., Zhu, D. and Liu, H. (2015) Alterations in left ventricular function during intermittent hypoxia: possible involvement of O-GlcNAc protein and MAPK signaling. Int. J. Mol. Med. 36, 150-158 doi:10.3892/ijmm.2015.2198
35. Watson, L.J., Facundo, H.T., Ngoh, G.A., Ameen, M., Brainard, R.E., Lemma, K.M. et al. (2010) O-linked β-N-acetylglucosamine transferase is indispensable in the failing heart. Proc. Natl Acad. Sci. U.S.A. 107, 17797-17802 doi:10.1073/pnas.1001907107
36. Watson, L.J., Long, B.W., DeMartino, A.M., Brittian, K.R., Readnower, R.D., Brainard, R.E. et al. (2014) Cardiomyocyte Ogt is essential for postnatal viability. Am. J. Physiol. Heart Circ. Physiol. 306, H142-H153 doi:10.1152/ajpheart.00438.2013
37. Sack, M.N., Disch, D.L., Rockman, H.A. and Kelly, D.P. (1997) A role for Sp and nuclear receptor transcription factors in a cardiac hypertrophic growth a program. Proc. Natl Acad. Sci. U.S.A. 94, 6438-6443 doi:10.1073/pnas.94.12.6438
38. Majumdar, G., Wright, J., Markowitz, P., Martinez-Hernandez, A., Raghow, R. and Solomon, S.S. (2004) Insulin stimulates and diabetes inhibits O-linked N-acetylglucosamine transferase and O-glycosylation of Sp1. Diabetes 53, 3184-3192 doi:10.2337/diabetes.53.12.3184
39. Yang, X., Su, K., Roos, M.D., Chang, Q., Paterson, A.J. and Kudlow, J.E. (2001) O-linkage of N-acetylglucosamine to Sp1 activation domain inhibits its transcriptional capability. Proc. Natl Acad. Sci. U.S.A. 98, 6611-6616 doi:10.1073/pnas.111099998
40. Medford, H.M., Cox, E.J., Miller, L.E. and Marsh, S.A. (2014) Consuming a Western diet for two weeks suppresses fetal genes in mouse hearts. Am. J. Physiol. Regul. Integr. Comp. Physiol. 306, R519-R526 doi:10.1152/ajpregu.00253.2013
41. Cox, E.J. and Marsh, S.A. (2013) Exercise and diabetes have opposite effects on the assembly and O-GlcNAc modification of the mSin3A/HDAC1/2 complex in the heart. Cardiovasc. Diabetol. 12, 101 doi:10.1186/1475-2840-12-101
42. Cannon, M.V., Sillje, H.H., Sijbesma, J.W., Vreeswijk-Baudoin, I., Ciapaite, J., van der Sluis, B. et al. (2015) Cardiac LXRα protects against pathological cardiac hypertrophy and dysfunction by enhancing glucose uptake and utilization. EMBO Mol. Med. 7, 1229-1243 doi:10.15252/emmm.201404669
43. Hulot, J.-S., Fauconnier, J., Ramanujam, D., Chaanine, A., Aubart, F., Sassi, Y. et al. (2011) Critical role for stromal interaction molecule 1 in cardiac hypertrophy. Circulation 124, 796-805 doi:10.1161/CIRCULATIONAHA.111.031229
44. Zhu-Mauldin, X., Marsh, S.A., Zou, L., Marchase, R.B. and Chatham, J.C. (2012) Modification of STIM1 by O-linked N-acetylglucosamine (O-GlcNAc) attenuates store-operated calcium entry in neonatal cardiomyocytes. J. Biol. Chem. 287, 39094-39106 doi:10.1074/jbc.M112.383778
45. van der Velden, J., Narolska, N., Lamberts, R., Boontje, N., Borbely, A., Zaremba, R. et al. (2006) Functional effects of protein kinase C-mediated myofilament phosphorylation in human myocardium. Cardiovasc. Res. 69, 876-887 doi:10.1016/j.cardiores.2005.11.021
46. Hamdani, N., Bishu, K.G., von Frieling-Salewsky, M., Redfield, M.M. and Linke, W.A. (2013) Deranged myofilament phosphorylation and function in experimental heart failure with preserved ejection fraction. Cardiovasc. Res. 97, 464-471 doi:10.1093/cvr/cvs353
47. van der Velden, J., Papp, Z., Zaremba, R., Boontje, N., Dejong, J., Owen, V. et al. (2003) Increased Ca2+-sensitivity of the contractile apparatus in end-stage human heart failure results from altered phosphorylation of contractile proteins. Cardiovasc. Res. 57, 37-47 doi:10.1016/S0008-6363(02)00606-5
48. Dubois-Deruy, E., Belliard, A., Mulder, P., Bouvet, M., Smet-Nocca, C., Janel, S. et al. (2015) Interplay between troponin T phosphorylation and O-N-acetylglucosaminylation in ischaemic heart failure. Cardiovasc. Res. 107, 56-65 doi:10.1093/cvr/cvv136
49. Ramirez-Correa, G.A., Jin, W., Wang, Z., Zhong, X., Gao, W.D., Dias, W.B. et al. (2008) O-linked GlcNAc modification of cardiac myofilament proteins: a novel regulator of myocardial contractile function. Circ. Res. 103, 1354-1358 doi:10.1161/CIRCRESAHA.108.184978
50. Muthusamy, S., DeMartino, A.M., Watson, L.J., Brittian, K.R., Zafir, A., Dassanayaka, S. et al. (2014) MicroRNA-539 is up-regulated in failing heart, and suppresses O-GlcNAcase expression. J. Biol. Chem. 289, 29665-29676 doi:10.1074/jbc.M114.578682
51. Lewis, B.A. and Hanover, J.A. (2014) O-GlcNAc and the epigenetic regulation of gene expression. J. Biol. Chem. 289, 34440-34448 doi:10.1074/jbc.R114.595439
52. Clark, R.J., McDonough, P.M., Swanson, E., Trost, S.U., Suzuki, M., Fukuda, M. et al. (2003) Diabetes and the accompanying hyperglycemia impairs cardiomyocyte calcium cycling through increased nuclear O-GlcNAcylation. J. Biol. Chem. 278, 44230-44237 doi:10.1074/jbc.M303810200
53. Hu, Y., Belke, D., Suarez, J., Swanson, E., Clark, R., Hoshijima, M. et al. (2005) Adenovirus-mediated overexpression of O-GlcNAcase improves contractile function in the diabetic heart. Circ. Res. 96, 1006-1013 doi:10.1161/01.RES.0000165478.06813.58
54. De Blasio, M.J., Prakoso, D., Qin, C., Rosli, S., Kiriazis, H., Du, X.-J. et al. (2016) Abstract 15267: cardiac-specific insulin-like growth factor-1 receptor (IGF-1R) expression targets maladaptive hexosamine biosynthesis and O-linked GlcNAc modification of sarco/endoplasmic reticulum Ca2+-ATPase (SERCA2a) in diabetic myocardium. Circulation 134(Suppl 1), A15267
55. Ramirez-Correa, G.A., Ma, J., Slawson, C., Zeidan, Q., Lugo-Fagundo, N.S., Xu, M. et al. (2015) Removal of abnormal myofilament O-GlcNAcylation restores Ca2+ sensitivity in diabetic cardiac muscle. Diabetes 64, 3573-3587 doi:10.2337/db14-1107
56. Gawlowski, T., Suarez, J., Scott, B., Torres-Gonzalez, M., Wang, H., Schwappacher, R. et al. (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 doi:10.1074/jbc.M112.390682
57. Dassanayaka, S., Readnower, R.D., Salabei, J.K., Long, B.W., Aird, A.L., Zheng, Y.-T. et al. (2015) High glucose induces mitochondrial dysfunction independently of protein O-GlcNAcylation. Biochem. J. 467, 115-126 doi:10.1042/BJ20141018
58. Banerjee, P.S., Ma, J. and Hart, G.W. (2015) Diabetes-associated dysregulation of O-GlcNAcylation in rat cardiac mitochondria. Proc. Natl Acad. Sci. U. S.A. 112, 6050-6055 doi:10.1073/pnas.1424017112
59. Ma, J., Liu, T., Wei, A.C., Banerjee, P., O'Rourke, B. and Hart, G.W. (2015) O-GlcNAcomic profiling identifies widespread O-GlcNAcylation in oxidative phosphorylation system regulating cardiac mitochondrial function. J. Biol. Chem. 290, 29141-29153 PMID:26446791
60. Ma, J., Banerjee, P., Whelan, S.A., Liu, T., Wei, A.C., Ramirez-Correa, G. et al. (2016) Comparative proteomics reveals dysregulated mitochondrial O-GlcNAcylation in diabetic hearts. J. Proteome Res. 15, 2254-2264 PMID:27213235
61. Wang, X., Feng, Z., Wang, X., Yang, L., Han, S., Cao, K. et al. (2016) O-GlcNAcase deficiency suppresses skeletal myogenesis and insulin sensitivity in mice through the modulation of mitochondrial homeostasis. Diabetologia 59, 1287-1296 doi:10.1007/s00125-016-3919-2
62. Federici, M., Menghini, R., Mauriello, A., Hribal, M.L., Ferrelli, F., Lauro, D. et al. (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 doi:10.1161/01.CIR.0000023043.02648.51
63. Beleznai, T. and Bagi, Z. (2012) Activation of hexosamine pathway impairs nitric oxide (NO)-dependent arteriolar dilations by increased protein O-GlcNAcylation. Vascul. Pharmacol. 56, 115-121 doi:10.1016/j.vph.2011.11.003
64. Makino, A., Dai, A., Han, Y., Youssef, K.D., Wang, W., Donthamsetty, R. et al. (2015) O-GlcNAcase overexpression reverses coronary endothelial cell dysfunction in type 1 diabetic mice. Am. J. Physiol. Cell Physiol. 309, C593-C599 doi:10.1152/ajpcell.00069.2015
65. Lima, V.V., Giachini, F.R., Matsumoto, T., Li, W., Bressan, A.F.M., Chawla, D. et al. (2016) High-fat diet increases O-GlcNAc levels in cerebral arteries: a link to vascular dysfunction associated with hyperlipidaemia/obesity? Clin. Sci. 130, 871-880 doi:10.1042/CS20150777
66. Heath, J.M., Sun, Y., Yuan, K., Bradley, W.E., Litovsky, S., Dell'Italia, L.J. et al. (2014) Activation of AKT by O-linked N-acetylglucosamine induces vascular calcification in diabetes mellitus. Circ. Res. 114, 1094-1102 doi:10.1161/CIRCRESAHA.114.302968
67. Lima, V.V., Giachini, F.R.C., Choi, H., Carneiro, F.S., Carneiro, Z.N., Fortes, Z.B. et al. (2009) Impaired vasodilator activity in deoxycorticosterone acetate-salt hypertension is associated with increased protein O-GlcNAcylation. Hypertension 53, 166-174 doi:10.1161/HYPERTENSIONAHA.108.116798
68. Lima, V.V., Giachini, F.R., Hardy, D.M., Webb, R.C. and Tostes, R.C. (2011) O-GlcNAcylation: a novel pathway contributing to the effects of endothelin in the vasculature. Am. J. Physiol. Regul. Integr. Comp. Physiol. 300, R236-R250 doi:10.1152/ajpregu.00230.2010
69. Xing, D., Feng, W., Not, L.G., Miller, A.P., Zhang, Y., Chen, Y.-F. 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-H342 doi:10.1152/ajpheart.01259.2007
70. Xing, D., Gong, K., Feng, W., Nozell, S.E., Chen, Y.-F., Chatham, J.C. et al. (2011) O-GlcNAc modification of NF?B p65 inhibits TNF-α-induced inflammatory mediator expression in rat aortic smooth muscle cells. PLoS ONE 6, e24021 doi:10.1371/journal.pone.0024021
71. Hilgers, R.H.P., Xing, D., Gong, K., Chen, Y.-F., Chatham, J.C. and Oparil, S. (2012) Acute O-GlcNAcylation prevents inflammation-induced vascular dysfunction. Am. J. Physiol. Heart Circ. Physiol. 303, H513-H522 doi:10.1152/ajpheart.01175.2011
72. Wang, Z.V., Deng, Y., Gao, N., Pedrozo, Z., Li, D.L., Morales, C.R. et al. (2014) Spliced X-box binding protein 1 couples the unfolded protein response to hexosamine biosynthetic pathway. Cell 156, 1179-1192 doi:10.1016/j.cell.2014.01.014