Toxicological Research

Korean Society of Toxicology & Korea Environmental Mutagen Society (한국독성학회)
권호 표지
DOI QR코드

DOI QR Code

Post-Translational Modification of Proteins in Toxicological Research: Focus on Lysine Acylation

  • Lee, Sangkyu (College of Pharmacy, Research Institute of Pharmaceutical Sciences, Kyungpook National University)
  • Received : 2013.04.18
  • Accepted : 2013.06.07
  • Published : 2013.06.30
Download PDF
⟨ Previous Next ⟩

Abstract

Toxicoproteomics integrates the proteomic knowledge into toxicology by enabling protein quantification in biofluids and tissues, thus taking toxicological research to the next level. Post-translational modification (PTM) alters the three-dimensional (3D) structure of proteins by covalently binding small molecules to them and therefore represents a major protein function diversification mechanism. Because of the crucial roles PTM plays in biological systems, the identification of novel PTMs and study of the role of PTMs are gaining much attention in proteomics research. Of the 300 known PTMs, protein acylation, including lysine formylation, acetylation, propionylation, butyrylation, malonylation, succinylation, and crotonylation, regulates the crucial functions of many eukaryotic proteins involved in cellular metabolism, cell cycle, aging, growth, angiogenesis, and cancer. Here, I reviewed recent studies regarding novel types of lysine acylation, their biological functions, and their applicationsin toxicoproteomics research.

Keywords

References

  1. Walsh, C.T., Garneau-Tsodikova, S. and Gatto, G.J. Jr. (2005) Protein posttranslational modifications: the chemistry of proteome diversifications. Angew. Chem. Int. Ed. Engl., 44, 7342-7372. https://doi.org/10.1002/anie.200501023
  2. Mann, M. and Jensen, O.N. (2003) Proteomic analysis of post-translational modifications. Nat. Biotechnol., 21, 255-261. https://doi.org/10.1038/nbt0303-255
  3. Cantin, G.T. and Yates, J.R. 3rd. (2004) Strategies for shotgun identification of post-translational modifications by mass spectrometry. J. Chromatogr. A, 1053, 7-14. https://doi.org/10.1016/j.chroma.2004.06.046
  4. Lu, Z., Cheng, Z., Zhao, Y. and Volchenboum, S.L. (2011c) Bioinformatic analysis and post-translational modification crosstalk prediction of lysine acetylation. PLoS One, 6, e28228. https://doi.org/10.1371/journal.pone.0028228
  5. Keck, J.M., Jones, M.H., Wong, C.C., Binkley, J., Chen, D., Jaspersen, S.L., Holinger, E.P., Xu, T., Niepel, M., Rout, M.P., Vogel, J., Sidow, A., Yates, J.R. 3rd. and Winey, M. (2011) A cell cycle phosphoproteome of the yeast centrosome. Science, 332, 1557-1561. https://doi.org/10.1126/science.1205193
  6. Hunter, T. (2000) Signaling--2000 and beyond. Cell, 100, 113-127. https://doi.org/10.1016/S0092-8674(00)81688-8
  7. Olsen, J.V., Vermeulen, M., Santamaria, A., Kumar, C., Miller, M.L., Jensen, L.J., Gnad, F., Cox, J., Jensen, T.S., Nigg, E.A., Brunak, S. and Mann, M. (2010) Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis. Sci. Signaling, 3, ra3. https://doi.org/10.1126/scisignal.2000475
  8. Norris, K.L., Lee, J.Y. and Yao, T.P. (2009) Acetylation goes global: the emergence of acetylation biology. Sci. Signaling, 2, pe76. https://doi.org/10.1126/scisignal.297pe76
  9. Kim, S.C., Sprung, R., Chen, Y., Xu, Y., Ball, H., Pei, J., Cheng, T., Kho, Y., Xiao, H., Xiao, L., Grishin, N.V., White, M., Yang, X.J. and Zhao, Y. (2006) Substrate and functional diversity of lysine acetylation revealed by a proteomics survey. Mol. Cell., 23, 607-618. https://doi.org/10.1016/j.molcel.2006.06.026
  10. Choudhary, C., Kumar, C., Gnad, F., Nielsen, M.L., Rehman, M., Walther, T.C., Olsen, J.V. and Mann, M. (2009) Lysine acetylation targets protein complexes and co-regulates major cellular functions. Science, 325, 834-840. https://doi.org/10.1126/science.1175371
  11. Lin, H., Su, X. and He, B. (2012) Protein lysine acylation and cysteine succination by intermediates of energy metabolism. ACS Chem. Biol., 7, 947-960. https://doi.org/10.1021/cb3001793
  12. Lu, J.Y., Lin, Y.Y., Sheu, J.C., Wu, J.T., Lee, F.J., Chen, Y., Lin, M.I., Chiang, F.T., Tai, T.Y., Berger, S.L., Zhao, Y., Tsai, K.S., Zhu, H., Chuang, L.M. and Boeke, J.D. (2011a) Acetylation of yeast AMPK controls intrinsic aging independently of caloric restriction. Cell, 146, 969-979. https://doi.org/10.1016/j.cell.2011.07.044
  13. Chuang, C., Lin, S.H., Huang, F., Pan, J., Josic, D. and Yu- Lee, L.Y. (2010) Acetylation of RNA processing proteins and cell cycle proteins in mitosis. J. Proteome Res., 9, 4554-4564. https://doi.org/10.1021/pr100281h
  14. Carafa, V., Nebbioso, A. and Altucci, L. (2012) Sirtuins and disease: the road ahead. Front. Pharmacol., 3, 4.
  15. Wang, Q., Zhang, Y., Yang, C., Xiong, H., Lin, Y., Yao, J., Li, H., Xie, L., Zhao, W., Yao, Y., Ning, Z.B., Zeng, R., Xiong, Y., Guan, K.L., Zhao, S. and Zhao, G.P. (2010) Acetylation of metabolic enzymes coordinates carbon source utilization and metabolic flux. Science, 327, 1004-1007. https://doi.org/10.1126/science.1179687
  16. Zhao, S., Xu, W., Jiang, W., Yu, W., Lin, Y., Zhang, T., Yao, J., Zhou, L., Zeng, Y., Li, H., Li, Y., Shi, J., An, W., Hancock, S.M., He, F., Qin, L., Chin, J., Yang, P., Chen, X., Lei, Q., Xiong, Y. and Guan, K.L. (2010) Regulation of cellular metabolism by protein lysine acetylation. Science, 327, 1000-1004. https://doi.org/10.1126/science.1179689
  17. Chen, Y., Sprung, R., Tang, Y., Ball, H., Sangras, B., Kim, S.C., Falck, J.R., Peng, J., Gu, W. and Zhao, Y. (2007) Lysine propionylation and butyrylation are novel post-translational modifications in histones. Mol. Cell. Proteomics, 6, 812-819. https://doi.org/10.1074/mcp.M700021-MCP200
  18. Cronican, A.A., Fitz, N.F., Carter, A., Saleem, M., Shiva, S., Barchowsky, A., Koldamova, R., Schug, J. and Lefterov, I. (2013) Genome-wide alteration of histone H3K9 acetylation pattern in mouse offspring prenatally exposed to arsenic. PLoS One, 8, e53478. https://doi.org/10.1371/journal.pone.0053478
  19. Sebastian, C., Zwaans, B.M., Silberman, D.M., Gymrek, M., Goren, A., Zhong, L., Ram, O., Truelove, J., Guimaraes, A.R., Toiber, D., Cosentino, C., Greenson, J.K., MacDonald, A.I., McGlynn, L., Maxwell, F., Edwards, J., Giacosa, S., Guccione, E., Weissleder, R., Bernstein, B.E., Regev, A., Shiels, P.G., Lombard, D.B. and Mostoslavsky, R. (2012) The histone deacetylase SIRT6 is a tumor suppressor that controls cancer metabolism. Cell, 151, 1185-1199. https://doi.org/10.1016/j.cell.2012.10.047
  20. Lu, Z., Bourdi, M., Li, J.H., Aponte, A.M., Chen, Y., Lombard, D.B., Gucek, M., Pohl, L.R. and Sack, M.N. (2011b) SIRT3-dependent deacetylation exacerbates acetaminophen hepatotoxicity. EMBO Rep., 12, 840-846 https://doi.org/10.1038/embor.2011.121
  21. Peserico, A. and Simone, C. (2011) Physical and functional HAT/HDAC interplay regulates protein acetylation balance. J. Biomed. Biotechnol., 2011, 371832.
  22. Yang, X.J. and Seto, E. (2008) Lysine acetylation: codified crosstalk with other posttranslational modifications. Mol. Cell., 31, 449-461. https://doi.org/10.1016/j.molcel.2008.07.002
  23. Shepard, B.D. and Tuma, P.L. (2009) Alcohol-induced protein hyperacetylation: mechanisms and consequences. World J. Gastroenterol., 15, 1219-1230. https://doi.org/10.3748/wjg.15.1219
  24. Fritz, K.S., Galligan, J.J., Hirschey, M.D., Verdin, E. and Petersen, D.R. (2012) Mitochondrial acetylome analysis in a mouse model of alcohol-induced liver injury utilizing SIRT3 knockout mice. J. Proteome Res., 11, 1633-1643. https://doi.org/10.1021/pr2008384
  25. You, M., Liang, X., Ajmo, J.M. and Ness, G.C. (2008) Involvement of mammalian sirtuin 1 in the action of ethanol in the liver. Am. J. Physiol. Gastrointest. Liver Physiol., 294, G892-G898. https://doi.org/10.1152/ajpgi.00575.2007
  26. Shimazu, T., Hirschey, M.D., Hua, L., Dittenhafer-Reed, K.E., Schwer, B., Lombard, D.B., Li, Y., Bunkenborg, J., Alt, F.W., Denu, J.M., Jacobson, M.P. and Verdin, E. (2010) SIRT3 deacetylates mitochondrial 3-hydroxy-3-methylglutaryl CoA synthase 2 and regulates ketone body production. Cell Metab., 12, 654-661. https://doi.org/10.1016/j.cmet.2010.11.003
  27. Qiu, X., Brown, K., Hirschey, M.D., Verdin, E. and Chen, D. (2010) Calorie restriction reduces oxidative stress by SIRT3- mediated SOD2 activation. Cell Metab., 12, 662-667. https://doi.org/10.1016/j.cmet.2010.11.015
  28. Hirschey, M.D., Shimazu, T., Goetzman, E., Jing, E., Schwer, B., Lombard, D.B., Grueter, C.A., Harris, C., Biddinger, S., Ilkayeva, O.R., Stevens, R.D., Li, Y., Saha, A.K., Ruderman, N.B., Bain, J.R., Newgard, C.B., Farese, R.V. Jr., Alt, F.W., Kahn, C.R. and Verdin, E. (2010) SIRT3 regulates mitochondrial fatty-acid oxidation by reversible enzyme deacetylation. Nature, 464, 121-125. https://doi.org/10.1038/nature08778
  29. Kendrick, A.A., Choudhury, M., Rahman, S.M., McCurdy, C.E., Friederich, M., Van Hove, J.L., Watson, P.A., Birdsey, N., Bao, J., Gius, D., Sack, M.N., Jing, E., Kahn, C.R., Friedman, J.E. and Jonscher, K.R. (2011) Fatty liver is associated with reduced SIRT3 activity and mitochondrial protein hyperacetylation. Biochem. J., 433, 505-514. https://doi.org/10.1042/BJ20100791
  30. Jo, W.J., Ren, X., Chu, F., Aleshin, M., Wintz, H., Burlingame, A., Smith, M.T., Vulpe, C.D. and Zhang, L. (2009) Acetylated H4K16 by MYST1 protects UROtsa cells from arsenic toxicity and is decreased following chronic arsenic exposure. Toxicol. Appl. Pharmacol., 241, 294-302. https://doi.org/10.1016/j.taap.2009.08.027
  31. Wilkins, M.R., Gasteiger, E., Gooley, A.A., Herbert, B.R., Molloy, M.P., Binz, P.A., Ou, K., Sanchez, J.C., Bairoch, A., Williams, K.L. and Hochstrasser, D.F. (1999) High-throughput mass spectrometric discovery of protein post-translational modifications. J. Mol. Biol., 289, 645-657. https://doi.org/10.1006/jmbi.1999.2794
  32. Oses-Prieto, J.A., Zhang, X. and Burlingame, A.L. (2007) Formation of epsilon-formyllysine on silver-stained proteins: implications for assignment of isobaric dimethylation sites by tandem mass spectrometry. Mol. Cell. Proteomics, 6, 181-192. https://doi.org/10.1074/mcp.M600279-MCP200
  33. Wisniewski, J.R., Zougman, A. and Mann, M. (2008) Nepsilon- formylation of lysine is a widespread post-translational modification of nuclear proteins occurring at residues involved in regulation of chromatin function. Nucleic Acids Res., 36, 570-577. https://doi.org/10.1093/nar/gkm1057
  34. Cai, H. and Guengerich, F.P. (2000) Acylation of protein lysines by trichloroethylene oxide. Chem. Res. Toxicol., 13, 327-335. https://doi.org/10.1021/tx000003p
  35. Jiang, T., Zhou, X., Taghizadeh, K., Dong, M. and Dedon, P.C. (2007) N-formylation of lysine in histone proteins as a secondary modification arising from oxidative DNA damage. Proc. Natl. Acad. Sci. U.S.A., 104, 60-65. https://doi.org/10.1073/pnas.0606775103
  36. Eilstein, J., Gimenez-Arnau, E., Duche, D., Rousset, F. and Lepoittevin, J.P. (2007) Mechanistic studies on the lysineinduced N-formylation of 2,5-dimethyl-p-benzoquinonediimine. Chem. Res. Toxicol., 20, 1155-1161. https://doi.org/10.1021/tx700040s
  37. Zhang, K., Chen, Y., Zhang, Z. and Zhao, Y. (2009) Identification and verification of lysine propionylation and butyrylation in yeast core histones using PTMap software. J. Proteome Res., 8, 900-906. https://doi.org/10.1021/pr8005155
  38. Cheng, Z., Tang, Y., Chen, Y., Kim, S., Liu, H., Li, S.S., Gu, W. and Zhao, Y. (2009) Molecular characterization of propionyllysines in non-histone proteins. Mol. Cell. Proteomics, 8, 45-52. https://doi.org/10.1074/mcp.M800224-MCP200
  39. Liu, B., Lin, Y., Darwanto, A., Song, X., Xu, G. and Zhang, K. (2009) Identification and characterization of propionylation at histone H3 lysine 23 in mammalian cells. J. Biol. Chem., 284, 32288-32295. https://doi.org/10.1074/jbc.M109.045856
  40. Es-Haghi, A., Shariatizi, S., Ebrahim-Habibi, A. and Nemat- Gorgani, M. (2012) Amyloid fibrillation in native and chemically- modified forms of carbonic anhydrase II: role of surface hydrophobicity. Biochim. Biophys. Acta, 1824, 468-477. https://doi.org/10.1016/j.bbapap.2011.12.010
  41. Peng, C., Lu, Z., Xie, Z., Cheng, Z., Chen, Y., Tan, M., Luo, H., Zhang, Y., He, W., Yang, K., Zwaans, B.M., Tishkoff, D., Ho, L., Lombard, D., He, T.C., Dai, J., Verdin, E., Ye, Y. and Zhao, Y. (2011) The first identification of lysine malonylation substrates and its regulatory enzyme. Mol. Cell. Proteomics, 10, M111.012658. https://doi.org/10.1074/mcp.M111.012658
  42. Xie, Z., Dai, J., Dai, L., Tan, M., Cheng, Z., Wu, Y., Boeke, J.D. and Zhao, Y. (2012) Lysine succinylation and lysine malonylation in histones. Mol. Cell. Proteomics, 11, 100-107. https://doi.org/10.1074/mcp.M111.015875
  43. Newman, J.C., He, W. and Verdin, E. (2012) Mitochondrial protein acylation and intermediary metabolism: regulation by sirtuins and implications for metabolic disease. J. Biol. Chem., 287, 42436-42443. https://doi.org/10.1074/jbc.R112.404863
  44. Saggerson, D. (2008) Malonyl-CoA, a key signaling molecule in mammalian cells. Annu. Rev. Nutr., 28, 253-272. https://doi.org/10.1146/annurev.nutr.28.061807.155434
  45. Montellier, E., Rousseaux, S., Zhao, Y. and Khochbin, S. (2012) Histone crotonylation specifically marks the haploid male germ cell gene expression program: post-meiotic malespecific gene expression. BioEssays, 34, 187-193. https://doi.org/10.1002/bies.201100141
  46. Tan, M., Luo, H., Lee, S., Jin, F., Yang, J.S., Montellier, E., Buchou, T., Cheng, Z., Rousseaux, S., Rajagopal, N., Lu, Z., Ye, Z., Zhu, Q., Wysocka, J., Ye, Y., Khochbin, S., Ren, B. and Zhao, Y. (2011) Identification of 67 histone marks and histone lysine crotonylation as a new type of histone modification. Cell, 146, 1016-1028. https://doi.org/10.1016/j.cell.2011.08.008
  47. George, J., Singh, R., Mahmood, Z. and Shukla, Y. (2010) Toxicoproteomics: new paradigms in toxicology research. Toxicol. Mech. Methods, 20, 415-423. https://doi.org/10.3109/15376511003667842
  48. Wetmore, B.A. and Merrick, B.A. (2004) Toxicoproteomics: proteomics applied to toxicology and pathology. Toxicol. Pathol., 32, 619-642. https://doi.org/10.1080/01926230490518244
  49. Beltrao, P., Albanese, V., Kenner, L.R., Swaney, D.L., Burlingame, A., Villen, J., Lim, W.A., Fraser, J.S., Frydman, J. and Krogan, N.J. (2012) Systematic functional prioritization of protein posttranslational modifications. Cell, 150, 413-425. https://doi.org/10.1016/j.cell.2012.05.036

Cited by

  1. Systematic Analysis of Mycobacterial Acylation Reveals First Example of Acylation-mediated Regulation of Enzyme Activity of a Bacterial Phosphatase vol.290, pp.43, 2015, https://doi.org/10.1074/jbc.M115.687269
  2. Lipids contribute to epigenetic control via chromatin structure and functions pp.2199-1006, 2015, https://doi.org/10.14293/S2199-1006.1.SOR-LIFE.AUXYTR.v2
  3. Lipids contribute to epigenetic control via chromatin structure and functions pp.2199-1006, 2015, https://doi.org/10.14293/S2199-1006.1.SOR-LIFE.AUXYTR.v1
  4. Toxicoproteomics in human health and disease: an update vol.13, pp.12, 2016, https://doi.org/10.1080/14789450.2016.1252676
  5. Self-Aggregating Deep Cavitand Acts as a Fluorescence Displacement Sensor for Lysine Methylation vol.138, pp.34, 2016, https://doi.org/10.1021/jacs.6b05897
  6. Post-Translational Modifications of Cardiac Mitochondrial Proteins in Cardiovascular Disease: Not Lost in Translation vol.46, pp.1, 2016, https://doi.org/10.4070/kcj.2016.46.1.1
  7. First profiling of lysine crotonylation of myofilament proteins and ribosomal proteins in zebrafish embryos vol.8, pp.1, 2018, https://doi.org/10.1038/s41598-018-22069-3
  8. Predicting lysine-malonylation sites of proteins using sequence and predicted structural features vol.39, pp.22, 2018, https://doi.org/10.1002/jcc.25353