Login Register Cart 0
Generic placeholder image

Protein & Peptide Letters

Editor-in-Chief

ISSN (Print): 0929-8665
ISSN (Online): 1875-5305

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Mini-Review Article

Aminoacyl-tRNA Synthetases, Indispensable Players in Lung Tumorigenesis

Author(s): Pratyasha Bhowal, Priyanka Biswas Karmakar, Debkanya Dey, Riya Manna, Debraj Roy and Rajat Banerjee*

Volume 29, Issue 3, 2022

Published on: 15 March, 2022

Page: [208 - 217] Pages: 10

DOI: 10.2174/0929866529666220110143520

Price: $65

Open Access Journals Promotions 2
Abstract

Being an essential enzyme in protein synthesis, the aminoacyl-tRNA synthetases (aaRSs) have a conserved function throughout evolution. However, research has uncovered altered expressions as well as interactions of aaRSs, in league with aaRS-interacting multi-functional proteins (AIMPs), forming a multi-tRNA synthetase complex (MSC) and divulging into their roles outside the range of protein synthesis. In this review, we have directed our focus into the rudimentary structure of this compact association and also how these aaRSs and AIMPs are involved in the maintenance and progression of lung cancer, the principal cause of most cancer-related deaths. There is substantial validation that suggests the crucial role of these prime housekeeping proteins in lung cancer regulation. Here, we have addressed the biological role that the three AIMPs and the aaRSs play in tumorigenesis, along with an outline of the different molecular mechanisms involved in the same. In conclusion, we have introduced the potentiality of these components as possible therapeutics for the evolution of new-age treatments of lung tumorigenesis.

Keywords: Aminoacyl-tRNA synthetases (aaRSs), AIMPs, MSC, lung cancer, signal pathways, inhibitors.

« Previous Next »
Graphical Abstract

[1]
Ros, E.; Torres, A.G.; Ribas de Pouplana, L. Learning from nature to expand the genetic code. Trends Biotechnol., 2021, 39(5), 460-473.
[http://dx.doi.org/10.1016/j.tibtech.2020.08.003] [PMID: 32896440]
[2]
Kim, S.; You, S.; Hwang, D. Aminoacyl-tRNA synthetases and tumorigenesis: More than housekeeping. Nat. Rev. Cancer, 2011, 11(10), 708-718.
[http://dx.doi.org/10.1038/nrc3124] [PMID: 21941282]
[3]
Kwon, N.H.; Fox, P.L.; Kim, S. Aminoacyl-tRNA synthetases as therapeutic targets. Nat. Rev. Drug Discov., 2019, 18(8), 629-650.
[http://dx.doi.org/10.1038/s41573-019-0026-3] [PMID: 31073243]
[4]
Pang, Y.L.; Poruri, K.; Martinis, S.A. tRNA synthetase: tRNA aminoacylation and beyond. Wiley Interdiscip. Rev. RNA, 2014, 5(4), 461-480.
[http://dx.doi.org/10.1002/wrna.1224] [PMID: 24706556]
[5]
Antonellis, A.; Green, E.D. The role of aminoacyl-tRNA synthetases in genetic diseases. Annu. Rev. Genomics Hum. Genet., 2008, 9, 87-107.
[http://dx.doi.org/10.1146/annurev.genom.9.081307.164204] [PMID: 18767960]
[6]
Eriani, G.; Delarue, M.; Poch, O.; Gangloff, J.; Moras, D. Partition of tRNA synthetases into two classes based on mutually exclusive sets of sequence motifs. Nature, 1990, 347(6289), 203-206.
[http://dx.doi.org/10.1038/347203a0] [PMID: 2203971]
[7]
Hyeon, D.Y.; Kim, J.H.; Ahn, T.J.; Cho, Y.; Hwang, D.; Kim, S. Evolution of the multi-tRNA synthetase complex and its role in cancer. J. Biol. Chem., 2019, 294(14), 5340-5351.
[http://dx.doi.org/10.1074/jbc.REV118.002958] [PMID: 30782841]
[8]
Han, J.M.; Kim, J.Y.; Kim, S. Molecular network and functional implications of macromolecular tRNA synthetase complex. Biochem. Biophys. Res. Commun., 2003, 303(4), 985-993.
[http://dx.doi.org/10.1016/S0006-291X(03)00485-6] [PMID: 12684031]
[9]
Havrylenko, S.; Mirande, M. Aminoacyl-tRNA synthetase complexes in evolution. Int. J. Mol. Sci., 2015, 16(3), 6571-6594.
[http://dx.doi.org/10.3390/ijms16036571] [PMID: 25807264]
[10]
Ahn, S.S.; Kim, J.O.; Yoon, T.; Song, J.J.; Park, Y.B.; Lee, S.W.; Park, S.G. Serum aminoacyl-tRNA synthetase-interacting multifunctional protein-1 can predict severe antineutrophil cytoplasmic antibody-associated vasculitis: A pilot monocentric study. BioMed Res. Int., 2019, 2019, 7508240.
[http://dx.doi.org/10.1155/2019/7508240] [PMID: 31236412]
[11]
Burastero, S.E.; Fabbri, M. Aminoacyl-tRNA synthetase-interacting multifunctional protein-1 (AIMP1): The member of a molecular hub with unexpected functions, including CD4 T cell homeostasis. Clin. Immunol., 2012, 143(3), 207-209.
[http://dx.doi.org/10.1016/j.clim.2012.03.006] [PMID: 22542741]
[12]
Accogli, A.; Guerrero, K.; D’Agostino, M.D.; Tran, L.; Cieuta-Walti, C.; Thiffault, I.; Chénier, S.; Schwartzentruber, J.; Majewski, J.; Bernard, G. Biallelic loss-of-function variants in aimp1 cause a rare neurodegenerative disease. J. Child Neurol., 2019, 34(2), 74-80.
[http://dx.doi.org/10.1177/0883073818811223] [PMID: 30486714]
[13]
Park, S.G.; Kang, Y.S.; Ahn, Y.H.; Lee, S.H.; Kim, K.R.; Kim, K.W.; Koh, G.Y.; Ko, Y.G.; Kim, S. Dose-dependent biphasic activity of tRNA synthetase-associating factor, p43, in angiogenesis. J. Biol. Chem., 2002, 277(47), 45243-45248.
[http://dx.doi.org/10.1074/jbc.M207934200] [PMID: 12237313]
[14]
Choi, J.W.; Um, J.Y.; Kundu, J.K.; Surh, Y.J.; Kim, S. Multidirectional tumor-suppressive activity of AIMP2/p38 and the enhanced susceptibility of AIMP2 heterozygous mice to carcinogenesis. Carcinogenesis, 2009, 30(9), 1638-1644.
[http://dx.doi.org/10.1093/carcin/bgp170] [PMID: 19622630]
[15]
Kim, D.; Kwon, N.H.; Kim, S. Association of aminoacyl-tRNA Synthetases with cancer. In: Aminoacyl-tRNA Synthetases in Biology and Medicine; Springer, 2014; pp. 207-245.
[http://dx.doi.org/10.1007/978-94-017-8701-7]
[16]
Kim, Y.W.; Kwon, C.; Liu, J.L.; Kim, S.H.; Kim, S. Cancer association study of aminoacyl-tRNA synthetase signaling network in glioblastoma. PLoS One, 2012, 7(8), e40960.
[http://dx.doi.org/10.1371/journal.pone.0040960] [PMID: 22952576]
[17]
Kim, J.H.; Lee, C.; Lee, M.; Wang, H.; Kim, K.; Park, S.J.; Yoon, I.; Jang, J.; Zhao, H.; Kim, H.K.; Kwon, N.H.; Jeong, S.J.; Yoo, H.C.; Kim, J.H.; Yang, J.S.; Lee, M.Y.; Lee, C.W.; Yun, J.; Oh, S.J.; Kang, J.S.; Martinis, S.A.; Hwang, K.Y.; Guo, M.; Han, G.; Han, J.M.; Kim, S. Control of leucine-dependent mTORC1 pathway through chemical intervention of leucyl-tRNA synthetase and RagD interaction. Nat. Commun., 2017, 8(1), 732.
[http://dx.doi.org/10.1038/s41467-017-00785-0] [PMID: 28963468]
[18]
Bray, F.; Ferlay, J.; Soerjomataram, I.; Siegel, R.L.; Torre, L.A.; Jemal, A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin., 2018, 68(6), 394-424.
[http://dx.doi.org/10.3322/caac.21492] [PMID: 30207593]
[19]
DeSantis, C.E.; Lin, C.C.; Mariotto, A.B.; Siegel, R.L.; Stein, K.D.; Kramer, J.L.; Alteri, R.; Robbins, A.S.; Jemal, A. Cancer treatment and survivorship statistics, 2014. CA Cancer J. Clin., 2014, 64(4), 252-271.
[http://dx.doi.org/10.3322/caac.21235] [PMID: 24890451]
[20]
Jemal, A.; Center, M.M.; DeSantis, C.; Ward, E.M. Global patterns of cancer incidence and mortality rates and trends. Cancer Epidemiol. Biomarkers Prev., 2010, 19(8), 1893-1907.
[http://dx.doi.org/10.1158/1055-9965.EPI-10-0437] [PMID: 20647400]
[21]
Jemal, A.; Siegel, R.; Ward, E.; Hao, Y.; Xu, J.; Murray, T.; Thun, M.J. Cancer statistics, 2008. CA Cancer J. Clin., 2008, 58(2), 71-96.
[http://dx.doi.org/10.3322/CA.2007.0010] [PMID: 18287387]
[22]
Charloux, A.; Quoix, E.; Wolkove, N.; Small, D.; Pauli, G.; Kreisman, H. The increasing incidence of lung adenocarcinoma: Reality or artefact? A review of the epidemiology of lung adenocarcinoma. Int. J. Epidemiol., 1997, 26(1), 14-23.
[http://dx.doi.org/10.1093/ije/26.1.14] [PMID: 9126499]
[23]
Ferlay, J.; Shin, H.R.; Bray, F.; Forman, D.; Mathers, C.; Parkin, D.M. Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int. J. Cancer, 2010, 127(12), 2893-2917.
[http://dx.doi.org/10.1002/ijc.25516] [PMID: 21351269]
[24]
Clark, S.B.; Alsubait, S. Non small cell lung cancer. In: StatPearls. Treasure Island (FL); StatPearls Publishing, 2021.
[25]
Yannay-Cohen, N.; Carmi-Levy, I.; Kay, G.; Yang, C.M.; Han, J.M.; Kemeny, D.M.; Kim, S.; Nechushtan, H.; Razin, E. LysRS serves as a key signaling molecule in the immune response by regulating gene expression. Mol. Cell, 2009, 34(5), 603-611.
[http://dx.doi.org/10.1016/j.molcel.2009.05.019] [PMID: 19524539]
[26]
Guo, M.; Schimmel, P. Essential nontranslational functions of tRNA synthetases. Nat. Chem. Biol., 2013, 9(3), 145-153.
[http://dx.doi.org/10.1038/nchembio.1158] [PMID: 23416400]
[27]
Ivakhno, S.S.; Kornelyuk, A.I. Cytokine-like activities of some aminoacyl-tRNA synthetases and auxiliary p43 cofactor of aminoacylation reaction and their role in oncogenesis. Exp. Oncol., 2004, 26(4), 250-255.
[PMID: 15627054]
[28]
Park, B.J.; Kang, J.W.; Lee, S.W.; Choi, S.J.; Shin, Y.K.; Ahn, Y.H.; Choi, Y.H.; Choi, D.; Lee, K.S.; Kim, S. The haploinsufficient tumor suppressor p18 upregulates p53 via interactions with ATM/ATR. Cell, 2005, 120(2), 209-221.
[http://dx.doi.org/10.1016/j.cell.2004.11.054] [PMID: 15680327]
[29]
Chang, S.H.; Chung, Y.S.; Hwang, S.K.; Kwon, J.T.; Minai-Tehrani, A.; Kim, S.; Park, S.B.; Kim, Y.S.; Cho, M.H. Lentiviral vector-mediated shRNA against AIMP2-DX2 suppresses lung cancer cell growth through blocking glucose uptake. Mol. Cells, 2012, 33(6), 553-562.
[http://dx.doi.org/10.1007/s10059-012-2269-2] [PMID: 22562359]
[30]
Hwang, S.K.; Chang, S.H.; Minai-Tehrani, A.; Kim, Y.S.; Cho, M.H. Lentivirus-AIMP2-DX2 shRNA suppresses cell proliferation by regulating Akt1 signaling pathway in the lungs of AIMP2 / mice. J. Aerosol Med. Pulm. Drug Deliv., 2013, 26(3), 165-173.
[http://dx.doi.org/10.1089/jamp.2011.0959] [PMID: 23517169]
[31]
Crick, F. On degenerate templates and the adaptor hypothesis: A note for the RNA tie club; Wellcome Library: UK, 1955, pp. 1-36.
[32]
Cusack, S. Aminoacyl-tRNA synthetases. Curr. Opin. Struct. Biol., 1997, 7(6), 881-889.
[http://dx.doi.org/10.1016/S0959-440X(97)80161-3] [PMID: 9434910]
[33]
Jakó, E.; Ittzés, P.; Szenes, A.; Kun, A.; Szathmáry, E.; Pál, G. In silico detection of tRNA sequence features characteristic to aminoacyl-tRNA synthetase class membership. Nucleic Acids Res., 2007, 35(16), 5593-5609.
[http://dx.doi.org/10.1093/nar/gkm598] [PMID: 17704131]
[34]
Perona, J.J.; Rould, M.A.; Steitz, T.A.; Risler, J.L.; Zelwer, C.; Brunie, S. Structural similarities in glutaminyl- and methionyl-tRNA synthetases suggest a common overall orientation of tRNA binding. Proc. Natl. Acad. Sci. USA, 1991, 88(7), 2903-2907.
[http://dx.doi.org/10.1073/pnas.88.7.2903] [PMID: 2011598]
[35]
Kaminska, M.; Shalak, V.; Mirande, M. The appended C-domain of human methionyl-tRNA synthetase has a tRNA-sequestering function. Biochemistry, 2001, 40(47), 14309-14316.
[http://dx.doi.org/10.1021/bi015670b] [PMID: 11714285]
[36]
Ghosh, A.; Sakaguchi, R.; Liu, C.; Vishveshwara, S.; Hou, Y-M. Allosteric communication in cysteinyl tRNA synthetase: A network of direct and indirect readout. J. Biol. Chem., 2011, 286(43), 37721-37731.
[http://dx.doi.org/10.1074/jbc.M111.246702] [PMID: 21890630]
[37]
Bullwinkle, T.J.; Ibba, M. Emergence and Evolution. In: Aminoacyl-tRNA Synthetases in Biology and Medicine; Kim, S., Ed.; Springer Netherlands, 2014; pp. 43-87.
[38]
Park, S.G.; Choi, E.C.; Kim, S. Aminoacyl-tRNA synthetase-interacting multifunctional proteins (AIMPs): A triad for cellular homeostasis. IUBMB Life, 2010, 62(4), 296-302.
[http://dx.doi.org/10.1002/iub.324] [PMID: 20306515]
[39]
Kim, J.Y.; Kang, Y.S.; Lee, J.W.; Kim, H.J.; Ahn, Y.H.; Park, H.; Ko, Y.G.; Kim, S. p38 is essential for the assembly and stability of macromolecular tRNA synthetase complex: Implications for its physiological significance. Proc. Natl. Acad. Sci. USA, 2002, 99(12), 7912-7916.
[http://dx.doi.org/10.1073/pnas.122110199] [PMID: 12060739]
[40]
Khan, K.; Baleanu-Gogonea, C.; Willard, B.; Gogonea, V.; Fox, P.L. 3-Dimensional architecture of the human multi-tRNA synthetase complex. Nucleic Acids Res., 2020, 48(15), 8740-8754.
[http://dx.doi.org/10.1093/nar/gkaa569] [PMID: 32644155]
[41]
Kong, J.; Kim, S. Cell-based analysis of pairwise interactions between the components of the multi-tRNA synthetase complex. FASEB J., 2020, 34(8), 10476-10488.
[http://dx.doi.org/10.1096/fj.202000418R] [PMID: 32539228]
[42]
Cho, H.Y.; Maeng, S.J.; Cho, H.J.; Choi, Y.S.; Chung, J.M.; Lee, S.; Kim, H.K.; Kim, J.H.; Eom, C.Y.; Kim, Y.G.; Guo, M.; Jung, H.S.; Kang, B.S.; Kim, S. Assembly of multi-tRNA synthetase complex via heterotetrameric glutathione transferase-homology domains. J. Biol. Chem., 2015, 290(49), 29313-29328.
[http://dx.doi.org/10.1074/jbc.M115.690867] [PMID: 26472928]
[43]
Fu, Y.; Kim, Y.; Jin, K.S.; Kim, H.S.; Kim, J.H.; Wang, D.; Park, M.; Jo, C.H.; Kwon, N.H.; Kim, D.; Kim, M.H.; Jeon, Y.H.; Hwang, K.Y.; Kim, S.; Cho, Y. Structure of the ArgRS-GlnRS-AIMP1 complex and its implications for mammalian translation. Proc. Natl. Acad. Sci. USA, 2014, 111(42), 15084-15089.
[http://dx.doi.org/10.1073/pnas.1408836111] [PMID: 25288775]
[44]
Han, J.M.; Lee, M.J.; Park, S.G.; Lee, S.H.; Razin, E.; Choi, E.C.; Kim, S. Hierarchical network between the components of the multi-tRNA synthetase complex: Implications for complex formation. J. Biol. Chem., 2006, 281(50), 38663-38667.
[http://dx.doi.org/10.1074/jbc.M605211200] [PMID: 17062567]
[45]
Ofir-Birin, Y.; Fang, P.; Bennett, S.P.; Zhang, H.M.; Wang, J.; Rachmin, I.; Shapiro, R.; Song, J.; Dagan, A.; Pozo, J.; Kim, S.; Marshall, A.G.; Schimmel, P.; Yang, X.L.; Nechushtan, H.; Razin, E.; Guo, M. Structural switch of lysyl-tRNA synthetase between translation and transcription. Mol. Cell, 2013, 49(1), 30-42.
[http://dx.doi.org/10.1016/j.molcel.2012.10.010] [PMID: 23159739]
[46]
Han, J.M.; Park, S.G.; Lee, Y.; Kim, S. Structural separation of different extracellular activities in aminoacyl-tRNA synthetase-interacting multi-functional protein, p43/AIMP1. Biochem. Biophys. Res. Commun., 2006, 342(1), 113-118.
[http://dx.doi.org/10.1016/j.bbrc.2006.01.117] [PMID: 16472771]
[47]
Cho, H.Y.; Lee, H.J.; Choi, Y.S.; Kim, D.K.; Jin, K.S.; Kim, S.; Kang, B.S. Symmetric assembly of a decameric subcomplex in human multi-tRNA synthetase complex via interactions between glutathione transferase-homology domains and aspartyl-tRNA synthetase. J. Mol. Biol., 2019, 431(22), 4475-4496.
[http://dx.doi.org/10.1016/j.jmb.2019.08.013] [PMID: 31473157]
[48]
Rho, S.B.; Lee, J.S.; Jeong, E.J.; Kim, K.S.; Kim, Y.G.; Kim, S. A multifunctional repeated motif is present in human bifunctional tRNA synthetase. J. Biol. Chem., 1998, 273(18), 11267-11273.
[http://dx.doi.org/10.1074/jbc.273.18.11267] [PMID: 9556618]
[49]
Park, S.G.; Jung, K.H.; Lee, J.S.; Jo, Y.J.; Motegi, H.; Kim, S.; Shiba, K. Precursor of pro-apoptotic cytokine modulates aminoacylation activity of tRNA synthetase. J. Biol. Chem., 1999, 274(24), 16673-16676.
[http://dx.doi.org/10.1074/jbc.274.24.16673] [PMID: 10358004]
[50]
Lee, S.W.; Kim, G.; Kim, S. Aminoacyl-tRNA synthetase-interacting multi-functional protein 1/p43: An emerging therapeutic protein working at systems level. Expert Opin. Drug Discov., 2008, 3(8), 945-957.
[http://dx.doi.org/10.1517/17460441.3.8.945] [PMID: 23484969]
[51]
Kim, M.J.; Park, B.J.; Kang, Y.S.; Kim, H.J.; Park, J.H.; Kang, J.W.; Lee, S.W.; Han, J.M.; Lee, H.W.; Kim, S. Downregulation of FUSE-binding protein and c-myc by tRNA synthetase cofactor p38 is required for lung cell differentiation. Nat. Genet., 2003, 34(3), 330-336.
[http://dx.doi.org/10.1038/ng1182] [PMID: 12819782]
[52]
Han, J.M.; Park, B.J.; Park, S.G.; Oh, Y.S.; Choi, S.J.; Lee, S.W.; Hwang, S.K.; Chang, S.H.; Cho, M.H.; Kim, S. AIMP2/p38, the scaffold for the multi-tRNA synthetase complex, responds to genotoxic stresses via p53. Proc. Natl. Acad. Sci. USA, 2008, 105(32), 11206-11211.
[http://dx.doi.org/10.1073/pnas.0800297105] [PMID: 18695251]
[53]
Yum, M.K.; Kang, J.S.; Lee, A.E.; Jo, Y.W.; Seo, J.Y.; Kim, H.A.; Kim, Y.Y.; Seong, J.; Lee, E.B.; Kim, J.H.; Han, J.M.; Kim, S.; Kong, Y.Y. AIMP2 controls intestinal stem cell compartments and tumorigenesis by modulating Wnt/β-Catenin signaling. Cancer Res., 2016, 76(15), 4559-4568.
[http://dx.doi.org/10.1158/0008-5472.CAN-15-3357] [PMID: 27262173]
[54]
Schiller, J.H.; Harrington, D.; Belani, C.P.; Langer, C.; Sandler, A.; Krook, J.; Zhu, J.; Johnson, D.H. Comparison of four chemotherapy regimens for advanced non-small-cell lung cancer. N. Engl. J. Med., 2002, 346(2), 92-98.
[http://dx.doi.org/10.1056/NEJMoa011954] [PMID: 11784875]
[55]
World Health Organization. Cancer. Available from: https://www.who.int/healthtopics/cancer#tab=tab_1
[56]
Brambilla, E.; Gazdar, A. Pathogenesis of lung cancer signalling pathways: Roadmap for therapies. Eur. Respir. J., 2009, 33(6), 1485-1497.
[http://dx.doi.org/10.1183/09031936.00014009] [PMID: 19483050]
[57]
Shtivelman, E.; Hensing, T.; Simon, G.R.; Dennis, P.A.; Otterson, G.A.; Bueno, R.; Salgia, R. Molecular pathways and therapeutic targets in lung cancer. Oncotarget, 2014, 5(6), 1392-1433.
[http://dx.doi.org/10.18632/oncotarget.1891] [PMID: 24722523]
[58]
Liu, T.C.; Jin, X.; Wang, Y.; Wang, K. Role of epidermal growth factor receptor in lung cancer and targeted therapies. Am. J. Cancer Res., 2017, 7(2), 187-202.
[PMID: 28337370]
[59]
Vicary, G.W.; Roman, J. Targeting the mammalian target of rapamycin in lung cancer. Am. J. Med. Sci., 2016, 352(5), 507-516.
[http://dx.doi.org/10.1016/j.amjms.2016.08.014] [PMID: 27865299]
[60]
Agarwal, S.; Bell, C.M.; Taylor, S.M.; Moran, R.G. p53 deletion or hotspot mutations enhance mTORC1 activity by altering lysosomal dynamics of TSC2 and Rheb. Mol. Cancer Res., 2016, 14(1), 66-77.
[http://dx.doi.org/10.1158/1541-7786.MCR-15-0159] [PMID: 26385560]
[61]
Ekman, S.; Wynes, M.W.; Hirsch, F.R. The mTOR pathway in lung cancer and implications for therapy and biomarker analysis. J. Thorac. Oncol., 2012, 7(6), 947-953.
[http://dx.doi.org/10.1097/JTO.0b013e31825581bd] [PMID: 22588151]
[62]
Brognard, J.; Clark, A.S.; Ni, Y.; Dennis, P.A. Akt/protein kinase B is constitutively active in non-small cell lung cancer cells and promotes cellular survival and resistance to chemotherapy and radiation. Cancer Res., 2001, 61(10), 3986-3997.
[PMID: 11358816]
[63]
Richards, E.W.; Long, C.L.; Nelson, K.M.; Tohver, O.K.; Pinkston, J.A.; Navari, R.M.; Blakemore, W.S. Protein turnover in advanced lung cancer patients. Metabolism, 1993, 42(3), 291-296.
[http://dx.doi.org/10.1016/0026-0495(93)90076-Z] [PMID: 8487646]
[64]
Yin, J.; Liu, W.; Li, R.; Liu, J.; Zhang, Y.; Tang, W.; Wang, K. IARS2 silencing induces non-small cell lung cancer cells proliferation inhibition, cell cycle arrest and promotes cell apoptosis. Neoplasma, 2016, 63(1), 64-71.
[http://dx.doi.org/10.4149/neo_2016_008] [PMID: 26639235]
[65]
Choi, J.W.; Kim, D.G.; Lee, A.E.; Kim, H.R.; Lee, J.Y.; Kwon, N.H.; Shin, Y.K.; Hwang, S.K.; Chang, S.H.; Cho, M.H.; Choi, Y.L.; Kim, J.; Oh, S.H.; Kim, B.; Kim, S.Y.; Jeon, H.S.; Park, J.Y.; Kang, H.P.; Park, B.J.; Han, J.M.; Kim, S. Cancer-associated splicing variant of tumor suppressor AIMP2/p38: Pathological implication in tumorigenesis. PLoS Genet., 2011, 7(3), e1001351.
[http://dx.doi.org/10.1371/journal.pgen.1001351] [PMID: 21483803]
[66]
Wang, D.; Zhao, R.; Qu, Y.Y.; Mei, X.Y.; Zhang, X.; Zhou, Q.; Li, Y.; Yang, S.B.; Zuo, Z.G.; Chen, Y.M.; Lin, Y.; Xu, W.; Chen, C.; Zhao, S.M.; Zhao, J.Y. Colonic lysine homocysteinylation induced by high-fat diet suppresses DNA damage repair. Cell Rep., 2018, 25(2), 398-412.e6.
[http://dx.doi.org/10.1016/j.celrep.2018.09.022] [PMID: 30304680]
[67]
Shin, S.H.; Kim, H.S.; Jung, S.H.; Xu, H.D.; Jeong, Y.B.; Chung, Y.J. Implication of leucyl-tRNA synthetase 1 (LARS1) over-expression in growth and migration of lung cancer cells detected by siRNA targeted knock-down analysis. Exp. Mol. Med., 2008, 40(2), 229-236.
[http://dx.doi.org/10.3858/emm.2008.40.2.229] [PMID: 18446061]
[68]
Janku, F.; Yap, T.A.; Meric-Bernstam, F. Targeting the PI3K pathway in cancer: Are we making headway? Nat. Rev. Clin. Oncol., 2018, 15(5), 273-291.
[http://dx.doi.org/10.1038/nrclinonc.2018.28] [PMID: 29508857]
[69]
Fang, Z.; Wang, X.; Yan, Q.; Zhang, S.; Li, Y. Knockdown of IARS2 suppressed growth of gastric cancer cells by regulating the phosphorylation of cell cycle-related proteins. Mol. Cell. Biochem., 2018, 443(1-2), 93-100.
[http://dx.doi.org/10.1007/s11010-017-3213-8] [PMID: 29071539]
[70]
Di, X.; Jin, X.; Ma, H.; Wang, R.; Cong, S.; Tian, C.; Liu, J.; Zhao, M.; Li, R.; Wang, K. The oncogene IARS2 promotes non-small cell lung cancer tumorigenesis by activating the AKT/MTOR pathway. Front. Oncol., 2019, 9, 393.
[http://dx.doi.org/10.3389/fonc.2019.00393] [PMID: 31157169]
[71]
Braun, C.J.; Zhang, X.; Savelyeva, I.; Wolff, S.; Moll, U.M.; Schepeler, T.; Ørntoft, T.F.; Andersen, C.L.; Dobbelstein, M. p53-Responsive micrornas 192 and 215 are capable of inducing cell cycle arrest. Cancer Res., 2008, 68(24), 10094-10104.
[http://dx.doi.org/10.1158/0008-5472.CAN-08-1569] [PMID: 19074875]
[72]
Ko, Y.G.; Kim, E.Y.; Kim, T.; Park, H.; Park, H.S.; Choi, E.J.; Kim, S. Glutamine-dependent antiapoptotic interaction of human glutaminyl-tRNA synthetase with apoptosis signal-regulating kinase 1. J. Biol. Chem., 2001, 276(8), 6030-6036.
[http://dx.doi.org/10.1074/jbc.M006189200] [PMID: 11096076]
[73]
Kim, E.Y.; Lee, J.G.; Lee, J.M.; Kim, A.; Yoo, H.C.; Kim, K.; Lee, M.; Lee, C.; Han, G.; Han, J.M.; Chang, Y.S. Therapeutic effects of the novel Leucyl-tRNA synthetase inhibitor BC-LI-0186 in non-small cell lung cancer. Ther. Adv. Med. Oncol., 2019, 11, 1758835919846798.
[http://dx.doi.org/10.1177/1758835919846798] [PMID: 31205503]
[74]
Kim, E.Y.; Jung, J.Y.; Kim, A.; Kim, K.; Chang, Y.S. Methionyl-tRNA synthetase overexpression is associated with poor clinical outcomes in non-small cell lung cancer. BMC Cancer, 2017, 17(1), 467.
[http://dx.doi.org/10.1186/s12885-017-3452-9] [PMID: 28679377]
[75]
Wolfson, R.L.; Chantranupong, L.; Saxton, R.A.; Shen, K.; Scaria, S.M.; Cantor, J.R.; Sabatini, D.M. Sestrin2 is a leucine sensor for the mTORC1 pathway. Science, 2016, 351(6268), 43-48.
[http://dx.doi.org/10.1126/science.aab2674] [PMID: 26449471]
[76]
Lee, Y.N.; Nechushtan, H.; Figov, N.; Razin, E. The function of lysyl-tRNA synthetase and Ap4A as signaling regulators of MITF activity in FcepsilonRI-activated mast cells. Immunity, 2004, 20(2), 145-151.
[http://dx.doi.org/10.1016/S1074-7613(04)00020-2] [PMID: 14975237]
[77]
Boulos, S.; Park, M.C.; Zeibak, M.; Foo, S.Y.; Jeon, Y.K.; Kim, Y.T.; Motzik, A.; Tshori, S.; Hamburger, T.; Kim, S.; Nechushtan, H.; Razin, E. Serine 207 phosphorylated lysyl-tRNA synthetase predicts disease-free survival of non-small-cell lung carcinoma. Oncotarget, 2017, 8(39), 65186-65198.
[http://dx.doi.org/10.18632/oncotarget.18053] [PMID: 29029422]
[78]
Rajendran, V.; Kalita, P.; Shukla, H.; Kumar, A.; Tripathi, T. Aminoacyl-tRNA synthetases: Structure, function, and drug discovery. Int. J. Biol. Macromol., 2018, 111, 400-414.
[http://dx.doi.org/10.1016/j.ijbiomac.2017.12.157] [PMID: 29305884]
[79]
Zhou, Z.; Sun, B.; Huang, S.; Yu, D.; Zhang, X. Roles of aminoacyl-tRNA synthetase-interacting multi-functional proteins in physiology and cancer. Cell Death Dis., 2020, 11(7), 579.
[http://dx.doi.org/10.1038/s41419-020-02794-2] [PMID: 32709848]
[80]
Gurung, P.M.; Veerakumarasivam, A.; Williamson, M.; Counsell, N.; Douglas, J.; Tan, W.S.; Feber, A.; Crabb, S.J.; Short, S.C.; Freeman, A.; Powles, T.; Hoskin, P.J.; West, C.M.; Kelly, J.D. Loss of expression of the tumour suppressor gene AIMP3 predicts survival following radiotherapy in muscle-invasive bladder cancer. Int. J. Cancer, 2015, 136(3), 709-720.
[PMID: 24917520]
[81]
Cao, Q.; Zhang, J.; Zhang, T. AIMP2-DX2 Promotes the proliferation, migration, and invasion of nasopharyngeal carcinoma cells. BioMed Res. Int., 2018, 2018, 9253036.
[http://dx.doi.org/10.1155/2018/9253036] [PMID: 29854811]
[82]
Kim, M.S.; Song, J.H.; Cohen, E.P.; Cho, D.; Kim, T.S. Aminoacyl tRNA Synthetase–interacting multifunctional protein 1 activates NK cells via macrophages in vitroandin vivo. J. Immunol., 2017, 198(10), 4140-4147.
[http://dx.doi.org/10.4049/jimmunol.1601558] [PMID: 28381637]
[83]
Hong, H.J.; Lim, H.X.; Song, J.H.; Lee, A.; Kim, E.; Cho, D.; Cohen, E.P.; Kim, T.S. Aminoacyl-tRNA synthetase-interacting multifunctional protein 1 suppresses tumor growth in breast cancer-bearing mice by negatively regulating myeloid-derived suppressor cell functions. Cancer Immunol. Immunother., 2016, 65(1), 61-72.
[http://dx.doi.org/10.1007/s00262-015-1777-2] [PMID: 26613952]
[84]
Kim, D.G.; Park, C.M.; Huddar, S.; Lim, S.; Kim, S.; Lee, S. Anticancer activity of pyrimethamine via ubiquitin mediated degradation of AIMP2-DX2. Molecules, 2020, 25(12), 2763.
[http://dx.doi.org/10.3390/molecules25122763]
[85]
Jung, J.Y.; Kim, E.Y.; Kim, A.; Chang, J.; Kwon, N.H.; Moon, Y.; Kang, E.J.; Sung, J.S.; Shim, H.; Kim, S.; Chang, Y.S. Ratio of autoantibodies of tumor suppressor AIMP2 and its oncogenic variant is associated with clinical outcome in lung cancer. J. Cancer, 2017, 8(8), 1347-1354.
[http://dx.doi.org/10.7150/jca.18450] [PMID: 28638448]
[86]
Kim, D.G.; Lee, J.Y.; Lee, J.H.; Cho, H.Y.; Kang, B.S.; Jang, S.Y.; Kim, M.H.; Guo, M.; Han, J.M.; Kim, S.J.; Kim, S. Oncogenic mutation of AIMP2/p38 inhibits its tumor-suppressive interaction with Smurf2. Cancer Res., 2016, 76(11), 3422-3436.
[http://dx.doi.org/10.1158/0008-5472.CAN-15-3255] [PMID: 27197155]
[87]
Ding, L.; Fang, Y.; Li, Y.; Hu, Q.; Ai, M.; Deng, K.; Huang, X.; Xin, H. AIMP3 inhibits cell growth and metastasis of lung adenocarcinoma through activating a miR-96-5p-AIMP3-p53 axis. J. Cell. Mol. Med., 2021, 25(6), 3019-3030.
[http://dx.doi.org/10.1111/jcmm.16344] [PMID: 33538115]
[88]
Sankaranarayanan, R.; Dock-Bregeon, A.C.; Rees, B.; Bovee, M.; Caillet, J.; Romby, P.; Francklyn, C.S.; Moras, D. Zinc ion mediated amino acid discrimination by threonyl-tRNA synthetase. Nat. Struct. Biol., 2000, 7(6), 461-465.
[http://dx.doi.org/10.1038/75856] [PMID: 10881191]
[89]
Bilokapic, S.; Maier, T.; Ahel, D.; Gruic-Sovulj, I.; Söll, D.; Weygand-Durasevic, I.; Ban, N. Structure of the unusual seryl-tRNA synthetase reveals a distinct zinc-dependent mode of substrate recognition. EMBO J., 2006, 25(11), 2498-2509.
[http://dx.doi.org/10.1038/sj.emboj.7601129] [PMID: 16675947]
[90]
Kumar, M.; Kumar, S.A.; Dimkovikj, A.; Baykal, L.N.; Banton, M.J.; Outlaw, M.M.; Polivka, K.E.; Hellmann-Whitaker, R.A. Zinc is the molecular “switch” that controls the catalytic cycle of bacterial leucyl-tRNA synthetase. J. Inorg. Biochem., 2015, 142, 59-67.
[http://dx.doi.org/10.1016/j.jinorgbio.2014.09.006] [PMID: 25450019]
[91]
Kim, S.H.; Bae, S.; Song, M. Recent development of Aminoacyl-tRNASynthetase inhibitors for human diseases: A future perspective. Biomolecules, 2020, 10, 1625.
[http://dx.doi.org/10.3390/biom10121625]
[92]
Zhong, Q.; Liu, Z.H.; Lin, Z.R.; Hu, Z.D.; Yuan, L.; Liu, Y.M.; Zhou, A.J.; Xu, L.H.; Hu, L.J.; Wang, Z.F.; Guan, X.Y.; Hao, J.J.; Lui, V.W.Y.; Guo, L.; Mai, H.Q.; Chen, M.Y.; Han, F.; Xia, Y.F.; Grandis, J.R.; Zhang, X.; Zeng, M.S. The RARS-MAD1L1 fusion gene induces cancer stem cell-like properties and therapeutic resistance in nasopharyngeal carcinoma. Clin. Cancer Res., 2018, 24(3), 659-673.
[http://dx.doi.org/10.1158/1078-0432.CCR-17-0352] [PMID: 29133573]
[93]
Kim, D.G.; Lee, J.Y.; Kwon, N.H.; Fang, P.; Zhang, Q.; Wang, J.; Young, N.L.; Guo, M.; Cho, H.Y.; Mushtaq, A.U.; Jeon, Y.H.; Choi, J.W.; Han, J.M.; Kang, H.W.; Joo, J.E.; Hur, Y.; Kang, W.; Yang, H.; Nam, D.H.; Lee, M.S.; Lee, J.W.; Kim, E.S.; Moon, A.; Kim, K.; Kim, D.; Kang, E.J.; Moon, Y.; Rhee, K.H.; Han, B.W.; Yang, J.S.; Han, G.; Yang, W.S.; Lee, C.; Wang, M.W.; Kim, S. Chemical inhibition of prometastatic lysyl-tRNA synthetase-laminin receptor interaction. Nat. Chem. Biol., 2014, 10(1), 29-34.
[http://dx.doi.org/10.1038/nchembio.1381] [PMID: 24212136]
[94]
Muguruma, H.; Yano, S.; Kakiuchi, S.; Uehara, H.; Kawatani, M.; Osada, H.; Sone, S.; Reveromycin, A. Reveromycin A inhibits osteolytic bone metastasis of small-cell lung cancer cells, SBC-5, through an antiosteoclastic activity. Clin. Cancer Res., 2005, 11(24 Pt 1), 8822-8828.
[http://dx.doi.org/10.1158/1078-0432.CCR-05-1335] [PMID: 16361571]
[95]
Lim, S.; Cho, H.Y.; Kim, D.G.; Roh, Y.; Son, S.Y.; Mushtaq, A.U.; Kim, M.; Bhattarai, D.; Sivaraman, A.; Lee, Y.; Lee, J.; Yang, W.S.; Kim, H.K.; Kim, M.H.; Lee, K.; Jeon, Y.H.; Kim, S. Targeting the interaction of AIMP2-DX2 with HSP70 suppresses cancer development. Nat. Chem. Biol., 2020, 16(1), 31-41.
[http://dx.doi.org/10.1038/s41589-019-0415-2] [PMID: 31792442]
[96]
Oh, A.Y.; Jung, Y.S.; Kim, J.; Lee, J.H.; Cho, J.H.; Chun, H.Y.; Park, S.; Park, H.; Lim, S.; Ha, N.C.; Park, J.S.; Park, C.S.; Song, G.Y.; Park, B.J. Inhibiting DX2-p14/ARF interaction exerts antitumor effects in lung cancer and delays tumor progression. Cancer Res., 2016, 76(16), 4791-4804.
[http://dx.doi.org/10.1158/0008-5472.CAN-15-1025] [PMID: 27302160]

Rights & Permissions Print Cite
Article Metrics
39
1
Wayfinder Image
Open Access Journals Promotions
World Antimicrobial Awareness Week
© 2024 Bentham Science Publishers | Privacy Policy