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Encyclopedia of Signaling Molecules pp 1–9Cite as

Serine/Threonine-Protein Kinase SMG1

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Synonyms

61E3.4; ATX; hSMG-1; KIAA0421; Lambda/iota protein kinase C-interacting protein; Lambda-interacting protein; LIP; Phosphatidylinositol 3-kinase-related kinase; Phosphatidylinositol 3-kinase-related protein kinase; PI-3-kinase-related kinase SMG-1; SMG1; SMG1 homolog, phosphatidylinositol 3-kinase-related kinase; Smg-1 homolog, phosphatidylinositol 3-kinase-related kinase (C. elegans); SMG-1; Suppressor with morphological effect on Genitalia 1

Historical Background

In 1993, the Anderson lab reported that loss of function mutations affecting seven Caenorhabditis elegans smg genes (smg-1~smg-7) eliminates nonsense-mediated mRNA decay (NMD), an mRNA surveillance mechanism which degrades mRNA containing nonsense mutation (Pulak and Anderson 1993). Later, the Anderson lab reported cloning of C. elegans smg-2, a nematode ortholog of UPF1, and in vivo phosphorylation of SMG-2 at 1999 (Page et al. 1999). SMG-2/UPF1 is an evolutionally conserved central component of NMD. In that paper,...

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References

  • Arias-Palomo E, Yamashita A, Fernandez IS, Nunez-Ramirez R, Bamba Y, Izumi N, et al. The nonsense-mediated mRNA decay SMG-1 kinase is regulated by large-scale conformational changes controlled by SMG-8. Genes Dev. 2011;25:153–64. doi:10.1101/gad.606911.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Azzalin CM, Reichenbach P, Khoriauli L, Giulotto E, Lingner J. Telomeric repeat containing RNA and RNA surveillance factors at mammalian chromosome ends. Science. 2007;318:798–801.

    Article  CAS  PubMed  Google Scholar 

  • Baretic D, Williams RL. PIKKs – the solenoid nest where partners and kinases meet. Curr Opin Struct Biol. 2014;29:134–42. doi:10.1016/j.sbi.2014.11.003.

    Article  CAS  PubMed  Google Scholar 

  • Brown JA, Roberts TL, Richards R, Woods R, Birrell G, Lim YC, et al. A novel role for hSMG-1 in stress granule formation. Mol Cell Biol. 2011;31:4417–29. doi:10.1128/MCB.05987-11.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Brumbaugh KM, Otterness DM, Geisen C, Oliveira V, Brognard J, Li X, et al. The mRNA surveillance protein hSMG-1 functions in genotoxic stress response pathways in mammalian cells. Mol Cell. 2004;14:585–98.

    Article  CAS  PubMed  Google Scholar 

  • Chakrabarti S, Bonneau F, Schussler S, Eppinger E, Conti E. Phospho-dependent and phospho-independent interactions of the helicase UPF1 with the NMD factors SMG5-SMG7 and SMG6. Nucleic Acids Res. 2014;42:9447–60. doi:10.1093/nar/gku578.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chen RQ, Yang QK, Chen YL, Oliveira VA, Dalton WS, Fearns C, et al. Kinome siRNA screen identifies SMG-1 as a negative regulator of hypoxia-inducible factor-1alpha in hypoxia. J Biol Chem. 2009;284:16752–8. doi:10.1074/jbc.M109.014316.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cho H, Han S, Choe J, Park SG, Choi SS, Kim YK. SMG5-PNRC2 is functionally dominant compared with SMG5-SMG7 in mammalian nonsense-mediated mRNA decay. Nucleic Acids Res. 2013a;41:1319–28. doi:10.1093/nar/gks1222.

    Article  CAS  PubMed  Google Scholar 

  • Cho H, Han S, Park OH, Kim YK. SMG1 regulates adipogenesis via targeting of staufen1-mediated mRNA decay. Biochim Biophys Acta. 2013b;1829:1276–87. doi:10.1016/j.bbagrm.2013.10.004.

    Article  CAS  PubMed  Google Scholar 

  • Denning G, Jamieson L, Maquat LE, Thompson EA, Fields AP. Cloning of a novel phosphatidylinositol kinase-related kinase: characterization of the human SMG-1 RNA surveillance protein. J Biol Chem. 2001;276:22709–14.

    Article  CAS  PubMed  Google Scholar 

  • Diaz-Meco MT, Municio MM, Sanchez P, Lozano J, Moscat J. Lambda-interacting protein, a novel protein that specifically interacts with the zinc finger domain of the atypical protein kinase C isotype lambda/iota and stimulates its kinase activity in vitro and in vivo. Mol Cell Biol. 1996;16:105–14.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Durand S, Franks TM, Lykke-Andersen J. Hyperphosphorylation amplifies UPF1 activity to resolve stalls in nonsense-mediated mRNA decay. Nat Commun. 2016;7:12434. doi:10.1038/ncomms12434.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Eberle AB, Lykke-Andersen S, Muhlemann O, Jensen TH. SMG6 promotes endonucleolytic cleavage of nonsense mRNA in human cells. Nat Struct Mol Biol. 2009;16:49–55. doi:10.1038/nsmb.1530.

    Article  CAS  PubMed  Google Scholar 

  • Fernandez IS, Yamashita A, Arias-Palomo E, Bamba Y, Bartolome RA, Canales MA, et al. Characterization of SMG-9, an essential component of the nonsense-mediated mRNA decay SMG1C complex. Nucleic Acids Res. 2011;39:347–58. doi:10.1093/nar/gkq749.

    Article  CAS  PubMed  Google Scholar 

  • Gatfield D, Unterholzner L, Ciccarelli FD, Bork P, Izaurralde E. Nonsense-mediated mRNA decay in Drosophila: at the intersection of the yeast and mammalian pathways. EMBO J. 2003;22:3960–70.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gehen SC, Staversky RJ, Bambara RA, Keng PC, O’Reilly MA. hSMG-1 and ATM sequentially and independently regulate the G1 checkpoint during oxidative stress. Oncogene. 2008;27:4065–74. doi:10.1038/onc.2008.48.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gewandter JS, Bambara RA, O'Reilly MA. The RNA surveillance protein SMG1 activates p53 in response to DNA double-strand breaks but not exogenously oxidized mRNA. Cell Cycle. 2011;10:2561–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gonzalez-Estevez C, Felix DA, Smith MD, Paps J, Morley SJ, James V, et al. SMG-1 and mTORC1 act antagonistically to regulate response to injury and growth in planarians. PLoS Genet. 2012;8:e1002619. doi:10.1371/journal.pgen.1002619.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gopalsamy A, Bennett EM, Shi M, Zhang WG, Bard J, Yu K. Identification of pyrimidine derivatives as hSMG-1 inhibitors. Bioorg Med Chem Lett. 2012;22:6636–41. doi:10.1016/j.bmcl.2012.08.107.

    Article  CAS  PubMed  Google Scholar 

  • Grimson A, O'Connor S, Newman CL, Anderson P. SMG-1 is a phosphatidylinositol kinase-related protein kinase required for nonsense-mediated mRNA Decay in Caenorhabditis elegans. Mol Cell Biol. 2004;24:7483–90.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gubanova E, Issaeva N, Gokturk C, Djureinovic T, Helleday T. SMG-1 suppresses CDK2 and tumor growth by regulating both the p53 and Cdc25A signaling pathways. Cell Cycle. 2013;12:3770–80. doi:10.4161/cc.26660.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Henderson-Smith A, Chow D, Meechoovet B, Aziz M, Jacobson SA, Shill HA, et al. SMG1 identified as a regulator of Parkinson's disease-associated alpha-synuclein through siRNA screening. PLoS One. 2013;8:e77711. doi:10.1371/journal.pone.0077711.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Huntzinger E, Kashima I, Fauser M, Sauliere J, Izaurralde E. SMG6 is the catalytic endonuclease that cleaves mRNAs containing nonsense codons in metazoan. RNA. 2008;14:2609–17.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ishikawa K, Nagase T, Nakajima D, Seki N, Ohira M, Miyajima N, et al. Prediction of the coding sequences of unidentified human genes. VIII. 78 new cDNA clones from brain which code for large proteins in vitro. DNA Res. 1997;4:307–13.

    Article  CAS  PubMed  Google Scholar 

  • Izumi N, Yamashita A, Hirano H, Ohno S. Heat shock protein 90 regulates phosphatidylinositol 3-kinase-related protein kinase family proteins together with the RUVBL1/2 and Tel2-containing co-factor complex. Cancer Sci. 2012a;103:50–7. doi:10.1111/j.1349-7006.2011.02112.x.

    Article  CAS  PubMed  Google Scholar 

  • Izumi N, Yamashita A, Iwamatsu A, Kurata R, Nakamura H, Saari B, et al. AAA+ proteins RUVBL1 and RUVBL2 coordinate PIKK activity and function in nonsense-mediated mRNA decay. Sci Signal. 2010;3:ra27. doi:10.1126/scisignal.2000468.

    Article  PubMed  Google Scholar 

  • Izumi N, Yamashita A, Ohno S. Integrated regulation of PIKK-mediated stress responses by AAA+ proteins RUVBL1 and RUVBL2. Nucleus. 2012b;3:29–43. doi:10.4161/nucl.18926.

    Article  PubMed  PubMed Central  Google Scholar 

  • Johns L, Grimson A, Kuchma SL, Newman CL, Anderson P. Caenorhabditis elegans SMG-2 selectively marks mRNAs containing premature translation termination codons. Mol Cell Biol. 2007;27:5630–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kashima I, Yamashita A, Izumi N, Kataoka N, Morishita R, Hoshino S, et al. Binding of a novel SMG-1-Upf1-eRF1-eRF3 complex (SURF) to the exon junction complex triggers Upf1 phosphorylation and nonsense-mediated mRNA decay. Genes Dev. 2006;20:355–67. doi:10.1101/gad.1389006.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kurosaki T, Li W, Hoque M, Popp MW, Ermolenko DN, Tian B, et al. A post-translational regulatory switch on UPF1 controls targeted mRNA degradation. Genes Dev. 2014;28:1900–16. doi:10.1101/gad.245506.114.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lloyd JP, Davies B. SMG1 is an ancient nonsense-mediated mRNA decay effector. Plant J. 2013;76:800–10. doi:10.1111/tpj.12329.

    Article  CAS  PubMed  Google Scholar 

  • Loh B, Jonas S, Izaurralde E. The SMG5-SMG7 heterodimer directly recruits the CCR4-NOT deadenylase complex to mRNAs containing nonsense codons via interaction with POP2. Genes Dev. 2013;27:2125–38. doi:10.1101/gad.226951.113.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lopez-Perrote A, Castano R, Melero R, Zamarro T, Kurosawa H, Ohnishi T, et al. Human nonsense-mediated mRNA decay factor UPF2 interacts directly with eRF3 and the SURF complex. Nucleic Acids Res. 2016;44:1909–23. doi:10.1093/nar/gkv1527.

    Article  PubMed  PubMed Central  Google Scholar 

  • Martin J, Han C, Gordon LA, Terry A, Prabhakar S, She X, et al. The sequence and analysis of duplication-rich human chromosome 16. Nature. 2004;432:988–94. doi:10.1038/nature03187.

    Article  CAS  PubMed  Google Scholar 

  • Masse I, Molin L, Mouchiroud L, Vanhems P, Palladino F, Billaud M, et al. A novel role for the SMG-1 kinase in lifespan and oxidative stress resistance in Caenorhabditis elegans. PLoS One. 2008;3:e3354. doi:10.1371/journal.pone.0003354.

    Article  PubMed  PubMed Central  Google Scholar 

  • McIlwain DR, Pan Q, Reilly PT, Elia AJ, McCracken S, Wakeham AC, et al. Smg1 is required for embryogenesis and regulates diverse genes via alternative splicing coupled to nonsense-mediated mRNA decay. Proc Natl Acad Sci U S A. 2010;107:12186–91. doi:10.1073/pnas.1007336107.

    Article  PubMed  PubMed Central  Google Scholar 

  • Melero R, Hug N, Lopez-Perrote A, Yamashita A, Caceres JF, Llorca O. The RNA helicase DHX34 functions as a scaffold for SMG1-mediated UPF1 phosphorylation. Nat Commun. 2016;7:10585. doi:10.1038/ncomms10585.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Melero R, Uchiyama A, Castano R, Kataoka N, Kurosawa H, Ohno S, et al. Structures of SMG1-UPFs complexes: SMG1 contributes to regulate UPF2-dependent activation of UPF1 in NMD. Structure. 2014;22:1105–19. doi:10.1016/j.str.2014.05.015.

    Article  CAS  PubMed  Google Scholar 

  • Meslin F, Hamai A, Mlecnik B, Rosselli F, Richon C, Jalil A, et al. hSMG-1 is a granzyme B-associated stress-responsive protein kinase. J Mol Med. 2011;89:411–21. doi:10.1007/s00109-010-0708-0.

    Article  CAS  PubMed  Google Scholar 

  • Morita T, Yamashita A, Kashima I, Ogata K, Ishiura S, Ohno S. Distant N- and C-terminal domains are required for intrinsic kinase activity of SMG-1, a critical component of nonsense-mediated mRNA decay. J Biol Chem. 2007;282:7799–808. doi:10.1074/jbc.M610159200.

    Article  CAS  PubMed  Google Scholar 

  • Nam SW, Park KC, Yang KJ, Lee B, Kim SW. Genetic screen identifies suppressor of morphogenesis in genitalia-1 (SMG-1) as a modulator of sorafenib resistance in hepatocellular carcinoma cell lines. Int J Oncol. 2014;45:1450–6. doi:10.3892/ijo.2014.2540.

    CAS  PubMed  Google Scholar 

  • Nicholson P, Josi C, Kurosawa H, Yamashita A, Muhlemann O. A novel phosphorylation-independent interaction between SMG6 and UPF1 is essential for human NMD. Nucleic Acids Res. 2014;42:9217–35. doi:10.1093/nar/gku645.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ohnishi T, Yamashita A, Kashima I, Schell T, Anders KR, Grimson A, et al. Phosphorylation of hUPF1 induces formation of mRNA surveillance complexes containing hSMG-5 and hSMG-7. Mol Cell. 2003;12:1187–200.

    Article  CAS  PubMed  Google Scholar 

  • Okada-Katsuhata Y, Yamashita A, Kutsuzawa K, Izumi N, Hirahara F, Ohno S. N- and C-terminal Upf1 phosphorylations create binding platforms for SMG-6 and SMG-5:SMG-7 during NMD. Nucleic Acids Res. 2012;40:1251–66. doi:10.1093/nar/gkr791.

    Article  CAS  PubMed  Google Scholar 

  • Oliveira V, Romanow WJ, Geisen C, Otterness DM, Mercurio F, Wang HG, et al. A protective role for the human SMG-1 kinase against tumor necrosis factor-alpha-induced apoptosis. J Biol Chem. 2008;283:13174–84. doi:10.1074/jbc.M708008200.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Page MF, Carr B, Anders KR, Grimson A, Anderson P. SMG-2 is a phosphorylated protein required for mRNA surveillance in Caenorhabditis elegans and related to Upf1p of yeast. Mol Cell Biol. 1999;19:5943–51.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pulak R, Anderson P. mRNA surveillance by the Caenorhabditis elegans smg genes. Genes Dev. 1993;7:1885–97.

    Article  CAS  PubMed  Google Scholar 

  • Schweingruber C, Rufener SC, Zund D, Yamashita A, Muhlemann O. Nonsense-mediated mRNA decay - mechanisms of substrate mRNA recognition and degradation in mammalian cells. Biochim Biophys Acta. 2013;1829:612–23. doi:10.1016/j.bbagrm.2013.02.005.

    Article  CAS  PubMed  Google Scholar 

  • Takai H, Wang RC, Takai KK, Yang H, de Lange T. Tel2 Regulates the Stability of PI3K-Related Protein Kinases. Cell. 2007;131:1248–59.

    Article  CAS  PubMed  Google Scholar 

  • von Morgen P, Horejsi Z, Macurek L. Substrate recognition and function of the R2TP complex in response to cellular stress. Front Genet. 2015;6:69. doi:10.3389/fgene.2015.00069.

    Google Scholar 

  • Wu G, Sinclair C, Hinson S, Ingle JN, Roche PC, Couch FJ. Structural analysis of the 17q22-23 amplicon identifies several independent targets of amplification in breast cancer cell lines and tumors. Cancer Res. 2001;61:4951–5.

    CAS  PubMed  Google Scholar 

  • Xia QS, Ishigaki Y, Zhao X, Shimasaki T, Nakajima H, Nakagawa H, et al. Human SMG-1 is involved in gemcitabine-induced primary microRNA-155/BIC up-regulation in human pancreatic cancer PANC-1 cells. Pancreas. 2011;40:55–60. doi:10.1097/MPA.0b013e3181e89f74.

    Article  CAS  PubMed  Google Scholar 

  • Yamashita A, Izumi N, Kashima I, Ohnishi T, Saari B, Katsuhata Y, et al. SMG-8 and SMG-9, two novel subunits of the SMG-1 complex, regulate remodeling of the mRNA surveillance complex during nonsense-mediated mRNA decay. Genes Dev. 2009;23:1091–105. doi:10.1101/gad.1767209.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yamashita A, Ohnishi T, Kashima I, Taya Y, Ohno S. Human SMG-1, a novel phosphatidylinositol 3-kinase-related protein kinase, associates with components of the mRNA surveillance complex and is involved in the regulation of nonsense-mediated mRNA decay. Genes Dev. 2001;15:2215–28. doi:10.1101/gad.913001.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgments

I would like to thank Ms. Kae Suzuki for reading manuscript.

Funding

This project was funded by the Japan Society for the Promotion of Science KAKENHI [20405020].

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Authors and Affiliations

  1. Department of Molecular Biology, Yokohama City University School of Medicine, 3-9, Fukuura, Kanazawa-ku, Yokohama, Kanagawa, 236-0004, Japan

    Akio Yamashita

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  1. Akio Yamashita
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Correspondence to Akio Yamashita .

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Editors and Affiliations

  1. Dept. Biological Science, Department of Molecular Science and Tech College of Natural Science, Suwon, Korea (Republic of)

    Sangdun Choi

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Yamashita, A. (2016). Serine/Threonine-Protein Kinase SMG1. In: Choi, S. (eds) Encyclopedia of Signaling Molecules. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-6438-9_101805-1

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  • DOI: https://doi.org/10.1007/978-1-4614-6438-9_101805-1

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