A Novel Tumor Suppressor Function of Glycine N-Methyltransferase Is Independent of Its Catalytic Activity but Requires Nuclear Localization

PLoS ONE

Volumn 8, Issue 7, 2013, Pages

  DebRoy, Suchandra ^a   Kramarenko, Inga I ^a   Ghose, Sampa ^a   Oleinik, Natalia V ^a   Krupenko, Sergey A ^a   Krupenko, Natalia I ^a  

^a MEDICAL UNIVERSITY OF SOUTH CAROLINA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

2 (2 AMINO 3 METHOXYPHENYL)CHROMONE; BENZYLOXYCARBONYLPHENYLALANYLALANYL FLUOROMETHYL KETONE; FOLIC ACID; GLYCINE METHYLTRANSFERASE; MITOGEN ACTIVATED PROTEIN KINASE 1; MITOGEN ACTIVATED PROTEIN KINASE 3; S ADENOSYLMETHIONINE;

ANTIPROLIFERATIVE ACTIVITY; APOPTOSIS; ARTICLE; CANCER CELL CULTURE; CANCER INHIBITION; CATALYSIS; CELL NUCLEUS; CELL SURVIVAL; CELL TRANSFORMATION; CELLULAR DISTRIBUTION; CONTROLLED STUDY; CYTOPLASM; CYTOTOXICITY; DOWN REGULATION; ENZYME ACTIVATION; ENZYME ACTIVITY; ENZYME BINDING; ENZYME LOCALIZATION; FIBROBLAST; GENETIC TRANSFECTION; HUMAN; HUMAN CELL; HUMAN TISSUE; IMMUNOHISTOCHEMISTRY; LIVER REGENERATION; MALIGNANT NEOPLASTIC DISEASE; NONHUMAN; PROTEIN EXPRESSION; RAT; SIGNAL TRANSDUCTION;

ANIMALS; APOPTOSIS; CATALYSIS; CELL CYCLE; CELL LINE; CELL NUCLEUS; CELL PROLIFERATION; DNA DAMAGE; ENZYME ACTIVATION; FOLIC ACID; GENE EXPRESSION; GLYCINE N-METHYLTRANSFERASE; HUMANS; MICE; MODELS, MOLECULAR; MOLECULAR CONFORMATION; MUTATION; PROTEIN BINDING; PROTEIN TRANSPORT; RECOMBINANT PROTEINS; TUMOR SUPPRESSOR PROTEINS;

EID: 84880807115     PISSN: None     EISSN: 19326203     Source Type: Journal    
DOI: 10.1371/journal.pone.0070062     Document Type: Article

References (54)

1. Martin JL, McMillan FM, (2002) SAM (dependent) I AM: the S-adenosylmethionine-dependent methyltransferase fold. Curr Opin Struct Biol 12: 783-793. doi:10.1016/S0959-440X(02)00391-3. PubMed: 12504684.
2. Luka Z, Mudd SH, Wagner C, (2009) Glycine N-methyltransferase and regulation of S-adenosylmethionine levels. J Biol Chem 284: 22507-22511. doi:10.1074/jbc.R109.019273. PubMed: 19483083.
3. Tibbetts AS, Appling DR, (2010) Compartmentalization of Mammalian folate-mediated one-carbon metabolism. Annu Rev Nutr 30: 57-81. doi:10.1146/annurev.nutr.012809.104810. PubMed: 20645850.
4. Hoffmann L, Brauers G, Gehrmann T, Häussinger D, Mayatepek E, et al. (2013) Osmotic regulation of hepatic betaine metabolism. Am J Physiol Gastrointest Liver Physiol, 304: G835-46. PubMed: 23449672.
5. Kumar N, Kishore N, (2013) Structure and effect of sarcosine on water and urea by using molecular dynamics simulations: Implications in protein stabilization. Biophys Chem 171: 9-15. doi:10.1016/j.bpc.2012.11.004. PubMed: 23266436.
6. Wagner C, (1995) Biochemical role of folate in cellular metabolism. In: Bailey LB, eds. Folate in Health and Disease. New York: Marcel Dekker, Inc. pp. pp. 23-42.
7. Takata Y, Huang Y, Komoto J, Yamada T, Konishi K, et al. (2003) Catalytic mechanism of glycine N-methyltransferase. Biochemistry 42: 8394-8402. doi:10.1021/bi034245a. PubMed: 12859184.
8. Luka Z, Capdevila A, Mato JM, Wagner C, (2006) A glycine N-methyltransferase knockout mouse model for humans with deficiency of this enzyme. Transgenic Res 15: 393-397. doi:10.1007/s11248-006-0008-1. PubMed: 16779654.
9. Yeo EJ, Wagner C, (1994) Tissue distribution of glycine N-methyltransferase, a major folate-binding protein of liver. Proc Natl Acad Sci U S A 91: 210-214. doi:10.1073/pnas.91.1.210. PubMed: 8278367.
10. Chen YM, Chen LY, Wong FH, Lee CM, Chang TJ, et al. (2000) Genomic structure, expression, and chromosomal localization of the human glycine N-methyltransferase gene. Genomics 66: 43-47. doi:10.1006/geno.2000.6188. PubMed: 10843803.
11. Wagner C, Briggs WT, Cook RJ, (1985) Inhibition of glycine N-methyltransferase activity by folate derivatives: implications for regulation of methyl group metabolism. Biochem Biophys Res Commun 127: 746-752. doi:10.1016/S0006-291X(85)80006-1. PubMed: 3838667.
12. Fu Z, Hu Y, Konishi K, Takata Y, Ogawa H, et al. (1996) Crystal structure of glycine N-methyltransferase from rat liver. Biochemistry 35: 11985-11993. doi:10.1021/bi961068n. PubMed: 8810903.
13. Pattanayek R, Newcomer ME, Wagner C, (1998) Crystal structure of apo-glycine N-methyltransferase (GNMT). Protein Sci 7: 1326-1331. doi:10.1002/pro.5560070608. PubMed: 9655336.
14. Krupenko NI, Wagner C, (1997) Transport of rat liver glycine N-methyltransferase into rat liver nuclei. J Biol Chem 272: 27140-27146. doi:10.1074/jbc.272.43.27140. PubMed: 9341155.
15. Luka Z, Pakhomova S, Loukachevitch LV, Egli M, Newcomer ME, et al. (2007) 5-methyltetrahydrofolate is bound in intersubunit areas of rat liver folate-binding protein glycine N-methyltransferase. J Biol Chem 282: 4069-4075. PubMed: 17158459.
16. Varela-Rey M, Fernández-Ramos D, Martínez-López N, Embade N, Gómez-Santos L, et al. (2009) Impaired liver regeneration in mice lacking glycine N-methyltransferase. Hepatology 50: 443-452. doi:10.1002/hep.23033. PubMed: 19582817.
17. Chen YM, Shiu JY, Tzeng SJ, Shih LS, Chen YJ, et al. (1998) Characterization of glycine-N-methyltransferase-gene expression in human hepatocellular carcinoma. Int J Cancer 75: 787-793. doi:10.1002/(SICI)1097-0215(19980302)75:5. PubMed: 9495250.
18. Tseng TL, Shih YP, Huang YC, Wang CK, Chen PH, et al. (2003) Genotypic and phenotypic characterization of a putative tumor susceptibility gene, GNMT, in liver cancer. Cancer Res 63: 647-654. PubMed: 12566309.
19. Liang CR, Leow CK, Neo JC, Tan GS, Lo SL, et al. (2005) Proteome analysis of human hepatocellular carcinoma tissues by two-dimensional difference gel electrophoresis and mass spectrometry. Proteomics 5: 2258-2271. doi:10.1002/pmic.200401256. PubMed: 15852300.
20. Huang YC, Lee CM, Chen M, Chung MY, Chang YH, et al. (2007) Haplotypes, loss of heterozygosity, and expression levels of glycine N-methyltransferase in prostate cancer. Clin Cancer Res 13: 1412-1420. doi:10.1158/1078-0432.CCR-06-1551. PubMed: 17332283.
21. Liu SP, Li YS, Chen YJ, Chiang EP, Li AF, et al. (2007) Glycine N-methyltransferase-/- mice develop chronic hepatitis and glycogen storage disease in the liver. Hepatology 46: 1413-1425. doi:10.1002/hep.21863. PubMed: 17937387.
22. Martínez-Chantar ML, Vázquez-Chantada M, Ariz U, Martínez N, Varela M, et al. (2008) Loss of the glycine N-methyltransferase gene leads to steatosis and hepatocellular carcinoma in mice. Hepatology 47: 1191-1199. PubMed: 18318442.
23. Raha A, Wagner C, MacDonald RG, Bresnick E, (1994) Rat liver cytosolic 4 S polycyclic aromatic hydrocarbon-binding protein is glycine N-methyltransferase. J Biol Chem 269: 5750-5756. PubMed: 8119914.
24. Bhat R, Weaver JA, Wagner C, Bodwell JE, Bresnick E, (1996) ATP depletion affects the phosphorylation state, ligand binding, and nuclear transport of the 4 S polycyclic aromatic hydrocarbon-binding protein in rat hepatoma cells. J Biol Chem 271: 32551-32556. doi:10.1074/jbc.271.51.32551. PubMed: 8955080.
25. Bhat R, Wagner C, Bresnick E, (1997) The homodimeric form of glycine N-methyltransferase acts as a polycyclic aromatic hydrocarbon-binding receptor. Biochemistry 36: 9906-9910. doi:10.1021/bi970159x. PubMed: 9245423.
26. Chen SY, Lin JR, Darbha R, Lin P, Liu TY, et al. (2004) Glycine N-methyltransferase tumor susceptibility gene in the benzo(a)pyrene-detoxification pathway. Cancer Res 64: 3617-3623. doi:10.1158/0008-5472.CAN-03-3726. PubMed: 15150120.
27. Lee CM, Chen SY, Lee YC, Huang CY, Chen YM, (2006) Benzo[a]pyrene and glycine N-methyltransferse interactions: gene expression profiles of the liver detoxification pathway. Toxicol Appl Pharmacol 214: 126-135. doi:10.1016/j.taap.2005.12.020. PubMed: 16545412.
28. Yen CH, Hung JH, Ueng YF, Liu SP, Chen SY, et al. (2009) Glycine N-methyltransferase affects the metabolism of aflatoxin B(1) and blocks its carcinogenic effect. Toxicol Appl Pharmacol 235: 296-304. doi:10.1016/j.taap.2008.12.013. PubMed: 19146867.
29. Yen CH, Hung JH, Ueng YF, Liu SP, Chen SY, et al. (2009) Glycine N-methyltransferase affects the metabolism of aflatoxin B1 and blocks its carcinogenic effect. Toxicol Appl Pharmacol 235: 296-304. doi:10.1016/j.taap.2008.12.013. PubMed: 19146867.
30. Michalopoulos GK, DeFrances MC, (1997) Liver regeneration. Science 276: 60-66. doi:10.1126/science.276.5309.60. PubMed: 9082986.
31. Oleinik NV, Krupenko NI, Reuland SN, Krupenko SA, (2006) Leucovorin-induced resistance against FDH growth suppressor effects occurs through DHFR up-regulation. Biochem Pharmacol 72: 256-266. doi:10.1016/j.bcp.2006.04.005. PubMed: 16712799.
32. Krupenko SA, Oleinik NV, (2002) 10-formyltetrahydrofolate dehydrogenase, one of the major folate enzymes, is down-regulated in tumor tissues and possesses suppressor effects on cancer cells. Cell Growth Differ 13: 227-236. PubMed: 12065246.
33. Denning G, Jean-Joseph B, Prince C, Durden DL, Vogt PK, (2007) A short N-terminal sequence of PTEN controls cytoplasmic localization and is required for suppression of cell growth. Oncogene 26: 3930-3940. doi:10.1038/sj.onc.1210175. PubMed: 17213812.
34. Fukuda M, Gotoh I, Gotoh Y, Nishida E, (1996) Cytoplasmic localization of mitogen-activated protein kinase kinase directed by its NH2-terminal, leucine-rich short amino acid sequence, which acts as a nuclear export signal. J Biol Chem 271: 20024-20028. doi:10.1074/jbc.271.33.20024. PubMed: 8702720.
35. Yoneda Y, Hieda M, Nagoshi E, Miyamoto Y, (1999) Nucleocytoplasmic protein transport and recycling of Ran. Cell Struct Funct 24: 425-433. doi:10.1247/csf.24.425. PubMed: 10698256.
36. Strickland KC, Krupenko NI, Krupenko SA, (2013) Molecular mechanisms underlying the potentially adverse effects of folate. Clin Chem Lab Med 51: 607-616. PubMed: 23241610.
37. Banerjee D, Mayer-Kuckuk P, Capiaux G, Budak-Alpdogan T, Gorlick R, et al. (2002) Novel aspects of resistance to drugs targeted to dihydrofolate reductase and thymidylate synthase. Biochim Biophys Acta 1587: 164-173. doi:10.1016/S0925-4439(02)00079-0. PubMed: 12084458.
38. Kelemen LE, (2006) The role of folate receptor alpha in cancer development, progression and treatment: cause, consequence or innocent bystander? Int J Cancer 119: 243-250. doi:10.1002/ijc.21712. PubMed: 16453285.
39. Jain M, Nilsson R, Sharma S, Madhusudhan N, Kitami T, et al. (2012) Metabolite profiling identifies a key role for glycine in rapid cancer cell proliferation. Science 336: 1040-1044. doi:10.1126/science.1218595. PubMed: 22628656.
40. Zhang WC, Shyh-Chang N, Yang H, Rai A, Umashankar S, et al. (2012) Glycine decarboxylase activity drives non-small cell lung cancer tumor-initiating cells and tumorigenesis. Cell 148: 259-272. doi:10.1016/j.cell.2011.11.050. PubMed: 22225612.
41. Kolch W, (2005) Coordinating ERK/MAPK signalling through scaffolds and inhibitors. Nat Rev Mol Cell Biol 6: 827-837. doi:10.1038/nrm1743. PubMed: 16227978.
42. Martínez-López N, García-Rodríguez JL, Varela-Rey M, Gutiérrez V, Fernández-Ramos D, et al. (2012) Hepatoma cells from mice deficient in glycine N-methyltransferase have increased RAS signaling and activation of liver kinase B1. Gastroenterology 143: 787-798 e781-713. doi:10.1053/j.gastro.2012.05.050. PubMed: 22687285.
43. Song YH, Shiota M, Kuroiwa K, Naito S, Oda Y, (2011) The important role of glycine N-methyltransferase in the carcinogenesis and progression of prostate cancer. Mod Pathol 24: 1272-1280. doi:10.1038/modpathol.2011.76. PubMed: 21572396.
44. Khan AP, Rajendiran TM, Ateeq B, Asangani IA, Athanikar JN, et al. (2013) The role of sarcosine metabolism in prostate cancer progression. Neoplasia 15: 491-501. PubMed: 23633921.
45. Seiler N, (2003) Thirty years of polyamine-related approaches to cancer therapy. Retrospect and prospect. Part 1. Selective enzyme inhibitors. Curr Drug Targets 4: 537-564. doi:10.2174/1389450033490885. PubMed: 14535654.
46. Thomas T, Thomas TJ, (2003) Polyamine metabolism and cancer. J Cell Mol Med 7: 113-126. doi:10.1111/j.1582-4934.2003.tb00210.x. PubMed: 12927050.
47. Sreekumar A, Poisson LM, Rajendiran TM, Khan AP, Cao Q, et al. (2009) Metabolomic profiles delineate potential role for sarcosine in prostate cancer progression. Nature 457: 910-914. doi:10.1038/nature07762. PubMed: 19212411.
48. Luka Z, Cerone R, Phillips JA 3rd, Mudd HS, Wagner C, (2002) Mutations in human glycine N-methyltransferase give insights into its role in methionine metabolism. Hum Genet 110: 68-74. doi:10.1007/s00439-001-0648-4. PubMed: 11810299.
49. Augoustides-Savvopoulou P, Luka Z, Karyda S, Stabler SP, Allen RH, et al. (2003) Glycine N-methyltransferase deficiency: a new patient with a novel mutation. J Inherit Metab Dis 26: 745-759. doi:10.1023/B:BOLI.0000009978.17777.33. PubMed: 14739680.
50. Luka Z, Wagner C, (2003) Effect of naturally occurring mutations in human glycine N-methyltransferase on activity and conformation. Biochem Biophys Res Commun 312: 1067-1072. doi:10.1016/j.bbrc.2003.11.037. PubMed: 14651980.
51. Stachowicz A, Suski M, Olszanecki R, Madej J, Okoń K, et al. (2012) Proteomic analysis of liver mitochondria of apolipoprotein E knockout mice treated with metformin. J Proteomics 77: 167-175. doi:10.1016/j.jprot.2012.08.015. PubMed: 22960565.
52. Liao YJ, Chen TL, Lee TS, Wang HA, Wang CK, et al. (2012) Glycine N-methyltransferase deficiency affects Niemann-Pick type C2 protein stability and regulates hepatic cholesterol homeostasis. Mol Med 18: 412-422. PubMed: 22183894.
53. Cook RJ, Wagner C, (1984) Glycine N-methyltransferase is a folate binding protein of rat liver cytosol. Proc Natl Acad Sci U S A 81: 3631-3634. doi:10.1073/pnas.81.12.3631. PubMed: 6587377.
54. Yeo EJ, Wagner C, (1992) Purification and properties of pancreatic glycine N-methyltransferase. J Biol Chem 267: 24669-24674. PubMed: 1332963.