PMID- 30782841 OWN - NLM STAT- MEDLINE DCOM- 20191016 LR - 20231011 IS - 1083-351X (Electronic) IS - 0021-9258 (Print) IS - 0021-9258 (Linking) VI - 294 IP - 14 DP - 2019 Apr 5 TI - Evolution of the multi-tRNA synthetase complex and its role in cancer. PG - 5340-5351 LID - 10.1074/jbc.REV118.002958 [doi] AB - Aminoacyl-tRNA synthetases (ARSs) are enzymes that ligate their cognate amino acids to tRNAs for protein synthesis. However, recent studies have shown that their functions are expanded beyond protein synthesis through the interactions with diverse cellular factors. In this review, we discuss how ARSs have evolved to expand and control their functions by forming protein assemblies. We particularly focus on a macromolecular ARS complex in eukaryotes, named multi-tRNA synthetase complex (MSC), which is proposed to provide a channel through which tRNAs reach bound ARSs to receive their cognate amino acid and transit further to the translation machinery. Approximately half of the ARSs assemble into the MSC through cis-acting noncatalytic domains attached to their catalytic domains and trans-acting factors. Evolution of the MSC included its functional expansion, during which the MSC interaction network was augmented by additional cellular pathways present in higher eukaryotes. We also discuss MSC components that could be functionally involved in the pathophysiology of tumorigenesis. For example, the activities of some trans-acting factors have tumor-suppressing effects or maintain DNA integrity and are functionally compromised in cancer. On the basis of Gene Ontology analyses, we propose that the regulatory activities of the MSC-associated ARSs mainly converge on five biological processes, including mammalian target of rapamycin (mTOR) and DNA repair pathways. Future studies are needed to investigate how the MSC-associated and free-ARSs interact with each other and other factors in the control of multiple cellular pathways, and how aberrant or disrupted interactions in the MSC can cause disease. CI - (c) 2019 Hyeon et al. FAU - Hyeon, Do Young AU - Hyeon DY AUID- ORCID: 0000-0002-6870-4827 AD - From the Center for Plant Aging Research, Institute for Basic Science, Daegu Gyeongbuk Institute of Science and Technology, Daegu 711-873. FAU - Kim, Jong Hyun AU - Kim JH AD - the Medicinal Bioconvergence Research Center and. AD - Department of Molecular Medicine and Biopharmaceutical Sciences, College of Pharmacy and Graduate School of Convergence Technologies, Seoul National University, Seoul 151-742. FAU - Ahn, Tae Jin AU - Ahn TJ AD - the Handong Global University, Nehemiah 316, Handong-ro 558, Pohang, and. FAU - Cho, Yeshin AU - Cho Y AUID- ORCID: 0000-0003-0702-012X AD - the Handong Global University, Nehemiah 316, Handong-ro 558, Pohang, and. FAU - Hwang, Daehee AU - Hwang D AD - From the Center for Plant Aging Research, Institute for Basic Science, Daegu Gyeongbuk Institute of Science and Technology, Daegu 711-873, daehee@snu.ac.kr. AD - the Department of New Biology, Daegu Gyeongbuk Institute of Science and Technology, Daegu 711-873, Republic of Korea. FAU - Kim, Sunghoon AU - Kim S AD - the Medicinal Bioconvergence Research Center and sungkim@snu.ac.kr. AD - Department of Molecular Medicine and Biopharmaceutical Sciences, College of Pharmacy and Graduate School of Convergence Technologies, Seoul National University, Seoul 151-742. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Review DEP - 20190219 PL - United States TA - J Biol Chem JT - The Journal of biological chemistry JID - 2985121R RN - 0 (Multienzyme Complexes) RN - 0 (Neoplasm Proteins) RN - EC 2.7.1.1 (MTOR protein, human) RN - EC 2.7.11.1 (TOR Serine-Threonine Kinases) RN - EC 6.1.1.- (Amino Acyl-tRNA Synthetases) SB - IM MH - *Amino Acyl-tRNA Synthetases/genetics/metabolism MH - Animals MH - DNA Repair MH - *Evolution, Molecular MH - Humans MH - *Multienzyme Complexes/genetics/metabolism MH - *Neoplasm Proteins/genetics/metabolism MH - *Neoplasms/enzymology/genetics/pathology MH - TOR Serine-Threonine Kinases/genetics/metabolism PMC - PMC6462501 OTO - NOTNLM OT - Aminoacyl-tRNA synthetases OT - Cancer OT - aminoacyl tRNA synthetase OT - cancer biology OT - intracellular processing OT - multi-tRNA synthetase complex OT - network analysis OT - pathology OT - protein synthesis OT - protein-protein interaction COIS- The authors declare that they have no conflicts of interest with the contents of this article EDAT- 2019/02/21 06:00 MHDA- 2019/10/17 06:00 PMCR- 2019/02/19 CRDT- 2019/02/21 06:00 PHST- 2019/02/21 06:00 [pubmed] PHST- 2019/10/17 06:00 [medline] PHST- 2019/02/21 06:00 [entrez] PHST- 2019/02/19 00:00 [pmc-release] AID - S0021-9258(20)35496-X [pii] AID - REV118.002958 [pii] AID - 10.1074/jbc.REV118.002958 [doi] PST - ppublish SO - J Biol Chem. 2019 Apr 5;294(14):5340-5351. doi: 10.1074/jbc.REV118.002958. Epub 2019 Feb 19.