Advertisement

Molecular Biology

, Volume 52, Issue 6, pp 823–835 | Cite as

Sestrins are Gatekeepers in the Way from Stress to Aging and Disease

  • A. A. Dalina
  • I. E. Kovaleva
  • A. V. BudanovEmail author
REVIEWS
  • 72 Downloads

Abstract—

Sestrins belong to a family of evolutionary conserved proteins which are found in the majority of animal species. While invertebrate genomes contain only one sestrin gene, mammalian and other vertebrate genomes comprise three highly homologous genes that encode Sestrin 1, 2 and 3 proteins (Sesn1, Sesn2 and Sesn3). Sestrins are activated in response to a variety of stimuli and trigger metabolic shifts promoting cell survival under stress conditions. Although cellular stress within an organism is often caused by external stimuli it can be induced by excess of cytokines, chemokines, reactive oxygen species which are produced during aberrant metabolic or immune processes and are involved in regulation of cell physiological states including cell death. Activation of sestrins facilitates cell adaptation to stress through stimulation of antioxidant response and autophagy through regulation of the signaling pathways mediated by AMPK and mTOR kinases. These activities are involved in protection of the organism during physical exercise and certain level of sestrins activity contributes to the development of age-related diseases. However, prolonged activation of sestrins under chronic stress may cause negative effects for the organism.

Keywords:

Sesn1 Sesn2 Sesn3 mTOR autophagy aging stress cell death 

Notes

REFERENCES

  1. 1.
    Velasco-Miguel S., Buckbinder L., Jean P., Gelbert L., Talbott R., Laidlaw J., Seizinger B., Kley N. 1999. PA26, a novel target of the p53 tumor suppressor and member of the GADD family of DNA damage and growth arrest inducible genes. Oncogene. 18, 127–137.CrossRefGoogle Scholar
  2. 2.
    Budanov A.V., Shoshani T., Faerman A., Zelin E., Kamer I., Kalinski H., Gorodin S., Fishman A., Chajut A., Einat P., Skaliter R., Gudkov A.V., Chumakov P.M., Feinstein E. 2002. Identification of a novel stress-responsive gene Hi95 involved in regulation of cell viability. Oncogene. 21, 6017–6031.CrossRefGoogle Scholar
  3. 3.
    Peeters H., Debeer P., Bairoch A., Wilquet V., Huysmans C., Parthoens E., Fryns J.P., Gewillig M., Nakamura Y., Niikawa N., van de Ven W., Devriendt K. 2003. PA26 is a candidate gene for heterotaxia in humans: Identification of a novel PA26-related gene family in human and mouse. Hum. Genet. 112, 573–580.Google Scholar
  4. 4.
    Budanov A.V., Lee J.H., Karin M. 2010. Stressin’ Sestrins take an aging fight. EMBO Mol. Med. 2, 388–400.CrossRefGoogle Scholar
  5. 5.
    Chen C.C., Jeon S.M., Bhaskar P.T., Nogueira V., Sundararajan D., Tonic I., Park Y., Hay N. 2010. FoxOs inhibit mTORC1 and activate Akt by inducing the expression of Sestrin3 and Rictor. Dev. Cell. 18, 592–604.CrossRefGoogle Scholar
  6. 6.
    Lee J.H., Budanov A.V., Park E.J., Birse R., Kim T.E., Perkins G.A., Ocorr K., Ellisman M.H., Bodmer R., Bier E., Karin M. 2010. Sestrin as a feedback inhibitor of TOR that prevents age-related pathologies. Science. 327, 1223–1228.CrossRefGoogle Scholar
  7. 7.
    Wolfson R.L., Sabatini D.M. 2017. The Dawn of the age of amino acid sensors for the mTORC1 pathway. Cell Metab. 26, 301–309.CrossRefGoogle Scholar
  8. 8.
    Budanov A.V., Sablina A.A., Feinstein E., Koonin E.V., Chumakov P.M. 2004. Regeneration of peroxiredoxins by p53-regulated sestrins, homologs of bacterial AhpD. Science. 304, 596–600.CrossRefGoogle Scholar
  9. 9.
    Bryk R., Lima C.D., Erdjument-Bromage H., Tempst P., Nathan C. 2002. Metabolic enzymes of mycobacteria linked to antioxidant defense by a thioredoxin-like protein. Science. 295, 1073–1077.CrossRefGoogle Scholar
  10. 10.
    Wolfson R.L., Chantranupong L., Saxton R.A., Shen K., Scaria S.M., Cantor J.R., Sabatini D.M. 2016. Sestrin2 is a leucine sensor for the mTORC1 pathway. Science. 351, 43–48.CrossRefGoogle Scholar
  11. 11.
    Kim H., An S., Ro S.H., Teixeira F., Park G.J., Kim C., Cho C.S., Kim J.S., Jakob U., Lee J.H., Cho U.S. 2015. Janus-faced Sestrin2 controls ROS and mTOR signalling through two separate functional domains. Nat. Commun. 6, 1–11.Google Scholar
  12. 12.
    Kimball S.R., Gordon B.S., Moyer J.E., Dennis M.D., Jefferson L.S. 2016. Leucine induced dephosphorylation of Sestrin2 promotes mTORC1 activation. Cell Signal. 28, 896–906.CrossRefGoogle Scholar
  13. 13.
    Budanov A.V. 2011. Stress-responsive sestrins link p53 with redox regulation and mammalian target of rapamycin signaling. Antioxid. Redox Signal. 15, 1679–1690.CrossRefGoogle Scholar
  14. 14.
    Kruiswijk F., Labuschagne C.F., Vousden K.H. 2015. p53 in survival, death and metabolic health: A lifeguard with a licence to kill. Nat. Rev. Mol. Cell Biol. 16, 393–405.CrossRefGoogle Scholar
  15. 15.
    Wei C.L., Wu Q., Vega V.B., Chiu K.P., Ng P., Zhang T., Shahab A., Yong H.C., Fu Y., Weng Z., Liu J., Zhao X.D., Chew J.L, Lee Y.L., Kuznetsov V.A., et al. 2006. A global map of p53 transcription-factor binding sites in the human genome. Cell. 124, 207–219.CrossRefGoogle Scholar
  16. 16.
    Ben-Sahra I., Dirat B., Laurent K., Puissant A., Auberger P., Budanov A., Tanti J.F., Bost F. 2013. Sestrin2 integrates Akt and mTOR signaling to protect cells against energetic stress-induced death. Cell Death Differ. 20, 611–619.CrossRefGoogle Scholar
  17. 17.
    Ding B., Parmigiani A., Divakaruni A.S., Archer K., Murphy A.N., Budanov A.V. 2016. Sestrin2 is induced by glucose starvation via the unfolded protein response and protects cells from non-canonical necroptotic cell death. Sci. Rep. 6, 22538.CrossRefGoogle Scholar
  18. 18.
    Parmigiani A., Budanov A.V. 2016. Sensing the environment through Sestrins: implications for cellular metabolism. Int. Rev. Cell. Mol. Biol. 327, 1–42.CrossRefGoogle Scholar
  19. 19.
    Ye J., Palm W., Peng M., King B., Lindsten T., Li M.O., Koumenis C., Thompson C.B. 2015. GCN2 sustains mTORC1 suppression upon amino acid deprivation by inducing Sestrin2. Genes Dev. 29, 2331–2336.CrossRefGoogle Scholar
  20. 20.
    Jegal K.H., Park S.M., Cho S.S., Byun S.H., Ku S.K., Kim S.C., Ki S.H., Cho I.J. 2017. Activating transcription factor 6-dependent sestrin 2 induction ameliorates ER stress-mediated liver injury. Biochim. Biophys. Acta. 1864, 1295–1307.CrossRefGoogle Scholar
  21. 21.
    Byun J.K., Choi Y.K., Kim J.H., Jeong J.Y., Jeon H.J., Kim M.K., Hwang I., Lee S.Y., Lee Y.M., Lee I.K., Park K.G. 2017. A positive feedback loop between Sestrin2 and mTORC2 is required for the survival of glutamine-depleted lung cancer cells. Cell Rep. 20, 586–599.CrossRefGoogle Scholar
  22. 22.
    Walter P., Ron D. 2011. The unfolded protein response: From stress pathway to homeostatic regulation. Science. 334, 1081–1086.CrossRefGoogle Scholar
  23. 23.
    Nogueira V., Park Y., Chen C.C., Xu P.Z., Chen M.L., Tonic I., Unterman T., Hay N. 2008. Akt determines replicative senescence and oxidative or oncogenic premature senescence and sensitizes cells to oxidative apoptosis. Cancer Cell. 14, 458–470.CrossRefGoogle Scholar
  24. 24.
    Hagenbuchner J., Kuznetsov A., Hermann M., Hausott B., Obexer P., Ausserlechner M.J. 2012. FOXO3-induced reactive oxygen species are regulated by BCL2L11 (Bim) and SESN3. J. Cell Sci. 125, 1191–1203.CrossRefGoogle Scholar
  25. 25.
    Eijkelenboom A., Burgering B.M. 2013. FOXOs: Signalling integrators for homeostasis maintenance. Nat. Rev. Mol. Cell Biol. 14, 83–97.CrossRefGoogle Scholar
  26. 26.
    Saxton R.A., Sabatini D.M. 2017. mTOR signaling in growth, metabolism, and disease. Cell. 169, 361–371.CrossRefGoogle Scholar
  27. 27.
    Wullschleger S., Loewith R., Hall M.N. 2006. TOR signaling in growth and metabolism. Cell. 124, 471–484.CrossRefGoogle Scholar
  28. 28.
    Mizushima N. 2007. Autophagy: Process and function. Genes Dev. 21, 2861–2873.CrossRefGoogle Scholar
  29. 29.
    Settembre C., Fraldi A., Medina D.L., Ballabio A. 2013. Signals from the lysosome: A control centre for cellular clearance and energy metabolism. Nat. Rev. Mol. Cell Biol. 14, 283–296.CrossRefGoogle Scholar
  30. 30.
    Manning B.D., Toker A. 2017. AKT/PKB signaling: Navigating the network. Cell. 169, 381–405.CrossRefGoogle Scholar
  31. 31.
    Sancak Y., Peterson T.R., Shaul Y.D., Lindquist R.A., Thoreen C.C., Bar-Peled L., Sabatini D.M. 2008. The Rag GTPases bind raptor and mediate amino acid signaling to mTORC1. Science. 320, 1496–1501.CrossRefGoogle Scholar
  32. 32.
    Bar-Peled L., Chantranupong L., Cherniack A.D., Chen W.W., Ottina K.A., Grabiner B.C., Spear E.D., Carter S.L., Meyerson M., Sabatini D.M. 2013. A tumor suppressor complex with GAP activity for the Rag GTPases that signal amino acid sufficiency to mTORC1. Science. 340, 1100–1106.CrossRefGoogle Scholar
  33. 33.
    Peng M., Yin N., Li M.O. 2017. SZT2 dictates GATOR control of mTORC1 signalling. Nature. 543, 433–437.CrossRefGoogle Scholar
  34. 34.
    Wolfson R.L., Chantranupong L., Wyant G.A., Gu X., Orozco J.M., Shen K., Condon K.J., Petri S., Kedir J., Scaria S.M., Abu-Remaileh M., Frankel W.N., Sabatini D.M. 2017. KICSTOR recruits GATOR1 to the lysosome and is necessary for nutrients to regulate mTORC1. Nature. 543, 438–442.CrossRefGoogle Scholar
  35. 35.
    Budanov A.V., Karin M. 2008. p53 target genes sestrin1 and sestrin2 connect genotoxic stress and mTOR signaling. Cell. 134, 451–460.CrossRefGoogle Scholar
  36. 36.
    Morrison A., Chen L., Wang J., Zhang M., Yang H., Ma Y., Budanov A., Lee J.H., Karin M., Li J. 2015. Sestrin2 promotes LKB1-mediated AMPK activation in the ischemic heart. FASEB J. 29, 408–417.CrossRefGoogle Scholar
  37. 37.
    Parmigiani A., Nourbakhsh A., Ding B., Wang W., Kim Y.C., Akopiants K., Guan K.L., Karin M., Budanov A.V. 2014. Sestrins inhibit mTORC1 kinase activation through the GATOR complex. Cell Rep. 9, 1281–1291.CrossRefGoogle Scholar
  38. 38.
    Chantranupong L., Wolfson R.L., Orozco J.M., Saxton R.A., Scaria S.M., Bar-Peled L., Spooner E., Isasa M., Gygi S.P., Sabatini D.M. 2014. The sestrins interact with GATOR2 to negatively regulate the amino-acid-sensing pathway upstream of mTORC1. Cell Rep. 9, 1–8.CrossRefGoogle Scholar
  39. 39.
    Saxton R.A., Knockenhauer K.E., Wolfson R.L., Chantranupong L., Pacold M.E., Wang T., Schwartz T.U., Sabatini D.M. 2016. Structural basis for leucine sensing by the Sestrin2-mTORC1 pathway. Science. 351, 53–58.CrossRefGoogle Scholar
  40. 40.
    Lee J.H., Budanov A.V., Talukdar S., Park E.J., Park H.L., Park H.W., Bandyopadhyay G., Li N., Aghajan M., Jang I., Wolfe A.M., Perkins G.A., Ellisman M.H., Bier E., Scadeng M., Foretz M., et al. 2012. Maintenance of metabolic homeostasis by Sestrin2 and Sestrin3. Cell Metab. 16, 311–321.CrossRefGoogle Scholar
  41. 41.
    Zhao B., Shah P., Budanov A.V., Qiang L., Ming M., Aplin A., Sims D.M., He Y.Y. 2014. Sestrin2 protein positively regulates AKT enzyme signaling and survival in human squamous cell carcinoma and melanoma cells. J. Biol. Chem. 289, 35806–35814.CrossRefGoogle Scholar
  42. 42.
    Tao R., Xiong X., Liangpunsakul S., Dong X.C. 2015. Sestrin 3 protein enhances hepatic insulin sensitivity by direct activation of the mTORC2-Akt signaling. Diabetes. 64, 1211–1223.CrossRefGoogle Scholar
  43. 43.
    Woo H.A., Bae S.H., Park S., Rhee S.G. 2009. Sestrin 2 is not a reductase for cysteine sulfinic acid of peroxiredoxins. Antioxid. Redox Signal. 11, 739–745.CrossRefGoogle Scholar
  44. 44.
    Green D.R., Galluzzi L., Kroemer G. 2011. Mitochondria and the autophagy-inflammation-cell death axis in organismal aging. Science. 333, 1109–1112.CrossRefGoogle Scholar
  45. 45.
    Li D.D., Sun T., Wu X.Q., Chen S.P., Deng R., Jiang S., Feng G.K., Pan J.X., Zhang X.S., Zeng Y.X., Zhu X.F. 2012. The inhibition of autophagy sensitises colon cancer cells with wild-type p53 but not mutant p53 to topotecan treatment. PLoS One. 7, e45058.CrossRefGoogle Scholar
  46. 46.
    Saveljeva S., Cleary P., Mnich K., Ayo A., Pakos-Zebrucka K., Patterson J.B., Logue S.E., Samali A. 2016. Endoplasmic reticulum stress-mediated induction of SESTRIN 2 potentiates cell survival. Oncotarget. 7, 12254–12266.CrossRefGoogle Scholar
  47. 47.
    Scheibye-Knudsen M., Fang E.F., Croteau D.L., Wilson D.M., Bohr V.A. 2015. Protecting the mitochondrial powerhouse. Trends Cell Biol. 25, 158–170.CrossRefGoogle Scholar
  48. 48.
    Kim M.J., Bae S.H., Ryu J.C., Kwon Y., Oh J.H., Kwon J., Moon J.S., Kim K., Miyawaki A., Lee M.G., Shin J., Kim Y.S., Kim C.H., Ryter S.W., Choi A.M., et al. 2016. SESN2/sestrin2 suppresses sepsis by inducing mitophagy and inhibiting NLRP3 activation in macrophages. Autophagy. 12, 1272–1291.CrossRefGoogle Scholar
  49. 49.
    Bae S.H., Sung S.H., Oh S.Y., Lim J.M., Lee S.K., Park Y.N., Lee H.E., Kang D., Rhee S.G. 2013. Sestrins activate Nrf2 by promoting p62-dependent autophagic degradation of Keap1 and prevent oxidative liver damage. Cell Metab. 17, 73–84.CrossRefGoogle Scholar
  50. 50.
    Tomasovic A., Kurrle N., Surun D., Heidler J., Husnjak K., Poser I., Schnutgen F., Scheibe S., Seimetz M., Jaksch P., Hyman A., Weissmann N., von Melchner H. 2015. Sestrin 2 protein regulates platelet-derived growth factor receptor beta (Pdgfrbeta) expression by modulating proteasomal and Nrf2 transcription factor functions. J. Biol. Chem. 290, 9738–9752.CrossRefGoogle Scholar
  51. 51.
    Liu S.Y., Lee Y.J., Lee T.C. 2011. Association of platelet-derived growth factor receptor beta accumulation with increased oxidative stress and cellular injury in sestrin 2 silenced human glioblastoma cells. FEBS Lett. 585, 1853–1858.CrossRefGoogle Scholar
  52. 52.
    Eid A.A., Lee D.Y., Roman L.J., Khazim K., Gorin Y. 2013. Sestrin 2 and AMPK connect hyperglycemia to Nox4-dependent endothelial nitric oxide synthase uncoupling and matrix protein expression. Mol. Cell Biol. 33, 3439–3460.CrossRefGoogle Scholar
  53. 53.
    Brace L.E., Vose S.C., Stanya K., Gathungu R.M., Marur V.R., Longchamp A., Trevino-Villarreal H., Mejia P., Vargas D., Inouye K., Bronson R.T., Lee C.H., Neilan E., Kristal B.S., Mitchell J.R. 2016. Increased oxidative phosphorylation in response to acute and chronic DNA damage. NPJ Aging Mech. Dis. 2, 16022.CrossRefGoogle Scholar
  54. 54.
    Garaeva A.A., Kovaleva I.E., Chumakov P.M., Evstafieva A.G. 2016. Mitochondrial dysfunction induces SESN2 gene expression through Activating Transcription Factor 4. Cell Cycle. 15, 64–71.CrossRefGoogle Scholar
  55. 55.
    Hou Y.S., Guan J.J., Xu H.D., Wu F., Sheng R., Qin Z.H. 2015. Sestrin2 protects dopaminergic cells against rotenone toxicity through AMPK-dependent autophagy activation. Mol. Cell Biol. 35, 2740–2751.CrossRefGoogle Scholar
  56. 56.
    Bruning A., Rahmeh M., Friese K. 2013. Nelfinavir and bortezomib inhibit mTOR activity via ATF4-mediated sestrin-2 regulation. Mol. Oncol. 7, 1012–1018.CrossRefGoogle Scholar
  57. 57.
    Sanli T., Linher-Melville K., Tsakiridis T., Singh G. 2012. Sestrin2 modulates AMPK subunit expression and its response to ionizing radiation in breast cancer cells. PLoS One. 7, e32035.CrossRefGoogle Scholar
  58. 58.
    Ding B., Parmigiani A., Yang C., Budanov A.V. 2015. Sestrin2 facilitates death receptor-induced apoptosis in lung adenocarcinoma cells through regulation of XIAP degradation. Cell Cycle. 14, 3231–3241.CrossRefGoogle Scholar
  59. 59.
    Lopez-Otin C., Blasco M.A., Partridge L., Serrano M., Kroemer G. 2013. The hallmarks of aging. Cell. 153, 1194–1217.CrossRefGoogle Scholar
  60. 60.
    Cornu M., Albert V., Hall M.N. 2013. mTOR in aging, metabolism, and cancer. Curr. Opin. Genet. Dev. 23, 53–62.CrossRefGoogle Scholar
  61. 61.
    Johnson S.C., Rabinovitch P.S., Kaeberlein M. 2013. mTOR is a key modulator of ageing and age-related disease. Nature. 493, 338–345.CrossRefGoogle Scholar
  62. 62.
    Kourtis N., Tavernarakis N. 2011. Cellular stress response pathways and ageing: Intricate molecular relationships. EMBO J. 30, 2520–2531.CrossRefGoogle Scholar
  63. 63.
    Yang Y.L., Loh K.S., Liou B.Y., Chu I.H., Kuo C.J., Chen H.D., Chen C.S. 2013. SESN-1 is a positive regulator of lifespan in Caenorhabditis elegans. Exp. Gerontol. 48, 371–379.CrossRefGoogle Scholar
  64. 64.
    Lee J.H., Budanov A.V., Karin M. 2013. Sestrins orchestrate cellular metabolism to attenuate aging. Cell Metab. 18, 792–801.CrossRefGoogle Scholar
  65. 65.
    Park H.W., Park H., Ro S.H., Jang I., Semple I.A., Kim D.N., Kim M., Nam M., Zhang D., Yin L., Lee J.H. 2014). Hepatoprotective role of Sestrin2 against chronic ER stress. Nat. Commun. 5, 4233.CrossRefGoogle Scholar
  66. 66.
    Quan N., Sun W., Wang L., Chen X., Bogan J.S., Zhou X., Cates C., Liu Q., Zheng Y., Li J. 2017. Sestrin2 prevents age-related intolerance to ischemia and reperfusion injury by modulating substrate metabolism. FASEB J. 31, 4153–4167.CrossRefGoogle Scholar
  67. 67.
    Hwang H.J., Jung T.W., Choi J.H., Lee H.J., Chung H.S., Seo J.A., Kim S.G., Kim N.H., Choi K.M., Choi D.S., Baic S.H., Yoo H.J. 2017. Knockdown of sestrin2 increases pro-inflammatory reactions and ER stress in the endothelium via an AMPK dependent mechanism. Biochim. Biophys. Acta. 1863, 1436–1444.CrossRefGoogle Scholar
  68. 68.
    Yang J.H., Kim K.M., Kim M.G., Seo K.H., Han J.Y., Ka S.O., Park B.H., Shin S.M., Ku S.K., Cho I.J., Ki S.H. 2015. Role of sestrin2 in the regulation of proinflammatory signaling in macrophages. Free Radic. Biol. Med. 78, 156–167.CrossRefGoogle Scholar
  69. 69.
    Kim M.G., Yang J.H., Kim K.M., Jang C.H., Jung J.Y., Cho I.J., Shin S.M., Ki S.H. 2015. Regulation of Toll-like receptor-mediated Sestrin2 induction by AP-1, Nrf2, and the ubiquitin-proteasome system in macrophages. Toxicol. Sci. 144, 425–435.CrossRefGoogle Scholar
  70. 70.
    Yang K., Xu C., Zhang Y., He S., Li D. 2017. Sestrin2 suppresses classically activated macrophages-mediated inflammatory response in myocardial infarction through inhibition of mTORC1 signaling. Front. Immunol. 8, 728.CrossRefGoogle Scholar
  71. 71.
    Chen Y.S., Chen S.D., Wu C.L., Huang S.S., Yang D.I. 2014. Induction of sestrin2 as an endogenous protective mechanism against amyloid beta-peptide neurotoxicity in primary cortical culture. Exp. Neurol. 253, 63–71.CrossRefGoogle Scholar
  72. 72.
    Kim J.R., Lee S.R., Chung H.J., Kim S., Baek S.H., Kim J.H., Kim Y.S. 2003. Identification of amyloid beta-peptide responsive genes by cDNA microarray technology: Involvement of RTP801 in amyloid beta-peptide toxicity. Exp. Mol. Med. 35, 403–411.CrossRefGoogle Scholar
  73. 73.
    Reddy K., Cusack C.L., Nnah I.C., Khayati K., Saqcena C., Huynh T.B., Noggle S.A., Ballabio A., Dobrowolski R. 2016. Dysregulation of nutrient sensing and CLEARance in presenilin deficiency. Cell Rep. 14, 2166–2179.CrossRefGoogle Scholar
  74. 74.
    Zhou D., Zhan C., Zhong Q., Li S. 2013. Upregulation of sestrin-2 expression via P53 protects against 1-methyl-4-phenylpyridinium (MPP+) neurotoxicity. J. Mol. Neurosci. 51, 967–975.CrossRefGoogle Scholar
  75. 75.
    Papadia S., Soriano F.X., Leveille F., Martel M.A., Dakin K.A., Hansen H.H., Kaindl A., Sifringer M., Fowler J., Stefovska V., McKenzie G., Craigon M., Corriveau R., Ghazal P., Horsburgh K., et al. 2008. Synaptic NMDA receptor activity boosts intrinsic antioxidant defenses. Nat. Neurosci. 11, 476–487.CrossRefGoogle Scholar
  76. 76.
    Kallenborn-Gerhardt W., Lu R., Syhr K.M., Heidler J., von Melchner H., Geisslinger G., Bangsow T., Schmidtko A. 2013. Antioxidant activity of sestrin 2 controls neuropathic pain after peripheral nerve injury. Antioxid. Redox Signal. 19, 2013–2023.CrossRefGoogle Scholar
  77. 77.
    Johnson M.R., Behmoaras J., Bottolo L., Krishnan M.L., Pernhorst K., Santoscoy P.L.M., Rossetti T., Speed D., Srivastava P.K., Chadeau-Hyam M., Hajji N., Dabrowska A., Rotival M., Razzaghi B., Kovac S., et al. 2015. Systems genetics identifies Sestrin 3 as a regulator of a proconvulsant gene network in human epileptic hippocampus. Nat. Commun. 6, 6031.CrossRefGoogle Scholar
  78. 78.
    Yeh S.H., Chen P.J., Chen H.L., Lai M.Y., Wang C.C., Chen D.S. 1994. Frequent genetic alterations at the distal region of chromosome 1p in human hepatocellular carcinomas. Cancer Res. 54, 4188–4192.Google Scholar
  79. 79.
    White P.S., Kaufman B.A., Marshall H.N., Brodeur G.M. 1993. Use of the single-strand conformation polymorphism technique to detect loss of heterozygosity in neuroblastoma. Genes Chromosomes Cancer. 7, 102–108.CrossRefGoogle Scholar
  80. 80.
    Nagai H., Negrini M., Carter S.L., Gillum D.R., Rosenberg A.L., Schwartz G.F., Croce C.M. 1995. Detection and cloning of a common region of loss of heterozygosity at chromosome 1p in breast cancer. Cancer Res. 55, 1752–1757.Google Scholar
  81. 81.
    Leister I., Weith A., Bruderlein S., Cziepluch C., Kangwanpong D., Schlag P., Schwab M. 1990. Human colorectal cancer: High frequency of deletions at chromosome 1p35. Cancer Res. 50, 7232–7235.Google Scholar
  82. 82.
    Lehmann S., Ogawa S., Raynaud S.D., Sanada M., Nannya Y., Ticchioni M., Bastard C., Kawamata N., Koeffler H.P. 2008. Molecular allelokaryotyping of early-stage, untreated chronic lymphocytic leukemia. Cancer. 112, 1296–1305.CrossRefGoogle Scholar
  83. 83.
    Thelander E.F., Ichimura K., Corcoran M., Barbany G., Nordgren A., Heyman M., Berglund M., Mungall A., Rosenquist R., Collins V.P., Grander D., Larsson C., Lagercrantz S. 2008. Characterization of 6q deletions in mature B cell lymphomas and childhood acute lymphoblastic leukemia. Leukemia Lymphoma. 49, 477–487.CrossRefGoogle Scholar
  84. 84.
    Hatano N., Nishikawa N.S., McElgunn C., Sarkar S., Ozawa K., Shibanaka Y., Nakajima M., Gohiji K., Kiyama R. 2001. A comprehensive analysis of loss of heterozygosity caused by hemizygous deletions in renal cell carcinoma using a subtraction library. Mol. Carcinogen. 31, 161–170.CrossRefGoogle Scholar
  85. 85.
    Carvalho B., Seruca R., Buys C.H., Kok K. 2002. Novel expressed sequences obtained by means of a suppression subtractive hybridisation analysis from the 6q21 region that is frequently deleted in gastric cancer. Eur. J. Cancer. 38, 1126–1132.CrossRefGoogle Scholar
  86. 86.
    Abe T., Makino N., Furukawa T., Ouyang H., Kimura M., Yatsuoka T., Yokoyama T., Inoue H., Fukushige S., Hoshi M., Hayashi Y., Sunamura M., Kobari M., Matsuno S., Horii A. 1999. Identification of three commonly deleted regions on chromosome arm 6q in human pancreatic cancer. Genes Chromosomes Cancer. 25, 60–64.CrossRefGoogle Scholar
  87. 87.
    Chen K.B., Xuan Y., Shi W.J., Chi F., Xing R., Zeng Y.C. 2016. Sestrin2 expression is a favorable prognostic factor in patients with non-small cell lung cancer. Am. J. Transl. Res. 8, 1903–1909.Google Scholar
  88. 88.
    Wei J.L., Fu Z.X., Fang M., Guo J.B., Zhao Q.N., Lu W.D., Zhou Q.Y. 2015. Decreased expression of sestrin 2 predicts unfavorable outcome in colorectal cancer. Oncol. Rep. 33, 1349–1357.CrossRefGoogle Scholar
  89. 89.
    Sablina A.A., Budanov A.V., Ilyinskaya G.V., Agapova L.S., Kravchenko J.E., Chumakov P.M. 2005. The antioxidant function of the p53 tumor suppressor. Nat. Med. 11, 1306–1313.CrossRefGoogle Scholar
  90. 90.
    Ro S.H., Xue X., Ramakrishnan S.K., Cho C.S., Namkoong S., Jang I., Semple I.A., Ho A., Park H.W., Shah Y.M., Lee J.H. 2016. Tumor suppressive role of sestrin2 during colitis and colon carcinogenesis. eLife. 5, e12204.CrossRefGoogle Scholar
  91. 91.
    Oricchio E., Katanayeva N., Donaldson M.C., Sungalee S., Pasion J.P., Beguelin W., Battistello E., Sanghvi V.R., Jiang M., Jiang Y., Teater M., Parmigiani A., Budanov A.V., Chan F.C., Shah S.P., et al. 2017. Genetic and epigenetic inactivation of SESTRIN1 controls mTORC1 and response to EZH2 inhibition in follicular lymphoma. Sci. Transl. Med. 9, eaak9969.Google Scholar
  92. 92.
    Zighelboim I., Goodfellow P.J., Schmidt A.P., Walls K.C., Mallon M.A., Mutch D.G., Yan P.S., Huang T.H., Powell M.A. 2007. Differential methylation hybridization array of endometrial cancers reveals two novel cancer-specific methylation markers. Clin. Cancer Res. 13, 2882–2889.CrossRefGoogle Scholar
  93. 93.
    Kopnin P.B., Agapova L.S., Kopnin B.P., Chumakov P.M. 2007. Repression of sestrin family genes contributes to oncogenic Ras-induced reactive oxygen species up-regulation and genetic instability. Cancer Res. 67, 4671–4678.CrossRefGoogle Scholar
  94. 94.
    Heidler J., Fysikopoulos A., Wempe F., Seimetz M., Bangsow T., Tomasovic A., Veit F., Scheibe S., Pichl A., Weisel F., Lloyd KC., Jaksch P., Klepetko W., Weissmann N., von Melchner H. 2013. Sestrin-2, a repressor of PDGFRbeta signalling, promotes cigarette-smoke-induced pulmonary emphysema in mice and is upregulated in individuals with COPD. Dis. Model. Mech. 6, 1378–1387.CrossRefGoogle Scholar
  95. 95.
    Wempe F., De-Zolt S., Koli K., Bangsow T., Parajuli N., Dumitrascu R., Sterner-Kock A., Weissmann N., Keski-Oja J., von Melchner H. 2010. Inactivation of sestrin 2 induces TGF-beta signaling and partially rescues pulmonary emphysema in a mouse model of COPD. Dis. Model. Mech. 3, 246–253.CrossRefGoogle Scholar
  96. 96.
    Mizumura K., Cloonan S.M., Nakahira K., Bhashyam A.R., Cervo M., Kitada T., Glass K., Owen C.A., Mahmood A., Washko G.R., Hashimoto S., Ryter S.W., Choi A.M. 2014. Mitophagy-dependent necroptosis contributes to the pathogenesis of COPD. J. Clin. Invest. 124, 3987–4003.CrossRefGoogle Scholar
  97. 97.
    Yoshida T., Mett I., Bhunia A.K., Bowman J., Perez M., Zhang L., Gandjeva A., Zhen L., Chukwueke U., Mao T., Richter A., Brown E., Ashush H., Notkin N., Gelfand A., et al. 2010. Rtp801, a suppressor of mTOR signaling, is an essential mediator of cigarette smoke-induced pulmonary injury and emphysema. Nat. Med. 16, 767–773.CrossRefGoogle Scholar
  98. 98.
    Zhang C., Sun W., Li J., Xiong B., Frye M.D., Ding D., Salvi R., Kim M.J., Someya S., Hu B.H. 2017. Loss of sestrin 2 potentiates the early onset of age-related sensory cell degeneration in the cochlea. Neuroscience. 361, 179–191.CrossRefGoogle Scholar
  99. 99.
    Ebnoether E., Ramseier A., Cortada M., Bodmer D., Levano-Huaman S. 2017. Sesn2 gene ablation enhances susceptibility to gentamicin-induced hair cell death via modulation of AMPK/mTOR signaling. Cell Death Discov. 3, 17024.CrossRefGoogle Scholar
  100. 100.
    Lanna A., Gomes D.C., Muller-Durovic B., McDonnell T., Escors D., Gilroy D.W., Lee J.H., Karin M., Akbar A.N. 2017. A sestrin-dependent Erk-Jnk-p38 MAPK activation complex inhibits immunity during aging. Nat. Immunol. 18, 354–363.CrossRefGoogle Scholar

Copyright information

© Pleiades Publishing, Inc. 2018

Authors and Affiliations

  • A. A. Dalina
    • 1
    • 2
  • I. E. Kovaleva
    • 3
  • A. V. Budanov
    • 1
    • 2
    Email author
  1. 1.Engelhardt Institute of Molecular Biology, Russian Academy of SciencesMoscowRussia
  2. 2.Trinity College DublinDublin 2Ireland
  3. 3.Belozersky Institute of Physical and Chemical Biology, Lomonosov Moscow State UniversityMoscowRussia

Personalised recommendations