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The Yeast GSK-3 Homologue Mck1 Is a Key Controller of Quiescence Entry and Chronological Lifespan


The vast majority of eukaryotic cells exist in a non-proliferating state known as G0. However, how cells transit into, and survive during, the G0 state is poorly understood. Dysregulation of the G0 state leads to age-related diseases such as Alzheimer’s or cancers. We have revealed that the yeast Mck1 and Rim15 kinases, which function downstream of the PKA and/or TOR signaling pathways, coordinate cell cycle progression, cell size homeostasis, and the acquisition of a variety of G0-specific characteristics during the transition into stationary phase. Failure of this coordination compromises the ability of early stationary-phase cells to exit from quiescence and severely shortens their chronological lifespan. Further genetic analyses suggest that the nutrient sensor Ras2 may antagonize G0 entry via at least two pathways, one through the negative regulation of the G0-specific effectors (Mck1 and Rim15) and the other possibly involving its functions in promoting respiratory growth, a phenotype also intricately modulated by Mck1 and Rim15. As Ras2 and Rim15 have homolog in both insects and/or mammals, the identification of the GSK-3 homologue Mck1 and the characterisation of its relationship with Rim15 and Ras2 in G0 entry could provide important clues to the regulation of these processes in more complex organisms.


Vyšlo v časopise: The Yeast GSK-3 Homologue Mck1 Is a Key Controller of Quiescence Entry and Chronological Lifespan. PLoS Genet 11(6): e32767. doi:10.1371/journal.pgen.1005282
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1005282

Souhrn

The vast majority of eukaryotic cells exist in a non-proliferating state known as G0. However, how cells transit into, and survive during, the G0 state is poorly understood. Dysregulation of the G0 state leads to age-related diseases such as Alzheimer’s or cancers. We have revealed that the yeast Mck1 and Rim15 kinases, which function downstream of the PKA and/or TOR signaling pathways, coordinate cell cycle progression, cell size homeostasis, and the acquisition of a variety of G0-specific characteristics during the transition into stationary phase. Failure of this coordination compromises the ability of early stationary-phase cells to exit from quiescence and severely shortens their chronological lifespan. Further genetic analyses suggest that the nutrient sensor Ras2 may antagonize G0 entry via at least two pathways, one through the negative regulation of the G0-specific effectors (Mck1 and Rim15) and the other possibly involving its functions in promoting respiratory growth, a phenotype also intricately modulated by Mck1 and Rim15. As Ras2 and Rim15 have homolog in both insects and/or mammals, the identification of the GSK-3 homologue Mck1 and the characterisation of its relationship with Rim15 and Ras2 in G0 entry could provide important clues to the regulation of these processes in more complex organisms.


Zdroje

1. Bartke A, Sun LY, Longo V (2013) Somatotropic signaling: trade-offs between growth, reproductive development, and longevity. Physiol Rev 93: 571–598. doi: 10.1152/physrev.00006.2012 23589828

2. Johnson SC, Rabinovitch PS, Kaeberlein M (2013) mTOR is a key modulator of ageing and age-related disease. Nature 493: 338–345. doi: 10.1038/nature11861 23325216

3. Kamada Y, Sekito T, Ohsumi Y (2004) Autophagy in yeast: a TOR-mediated response to nutrient starvation. Curr Top Microbiol Immunol 279: 73–84. 14560952

4. Gray JV, Petsko GA, Johnston GC, Ringe D, Singer RA, et al. (2004) "Sleeping beauty": quiescence in Saccharomyces cerevisiae. Microbiol Mol Biol Rev 68: 187–206. 15187181

5. De Virgilio C (2012) The essence of yeast quiescence. FEMS Microbiol Rev 36: 306–339. doi: 10.1111/j.1574-6976.2011.00287.x 21658086

6. Longo VD, Fabrizio P (2012) Chronological Aging in Saccharomyces cerevisiae. Subcell Biochem 57: 101–121. doi: 10.1007/978-94-007-2561-4_5 22094419

7. Powers RW 3rd, Kaeberlein M, Caldwell SD, Kennedy BK, Fields S (2006) Extension of chronological life span in yeast by decreased TOR pathway signaling. Genes Dev 20: 174–184. 16418483

8. Fabrizio P, Pozza F, Pletcher SD, Gendron CM, Longo VD (2001) Regulation of longevity and stress resistance by Sch9 in yeast. Science 292: 288–290. 11292860

9. Urban J, Soulard A, Huber A, Lippman S, Mukhopadhyay D, et al. (2007) Sch9 is a major target of TORC1 in Saccharomyces cerevisiae. Mol Cell 26: 663–674. 17560372

10. Fabrizio P, Liou LL, Moy VN, Diaspro A, Valentine JS, et al. (2003) SOD2 functions downstream of Sch9 to extend longevity in yeast. Genetics 163: 35–46. 12586694

11. Wei M, Fabrizio P, Hu J, Ge H, Cheng C, et al. (2008) Life span extension by calorie restriction depends on Rim15 and transcription factors downstream of Ras/PKA, Tor, and Sch9. PLoS Genet 4: e13. doi: 10.1371/journal.pgen.0040013 18225956

12. Ocampo A, Liu J, Schroeder EA, Shadel GS, Barrientos A (2012) Mitochondrial respiratory thresholds regulate yeast chronological life span and its extension by caloric restriction. Cell Metab 16: 55–67. doi: 10.1016/j.cmet.2012.05.013 22768839

13. Bonawitz ND, Chatenay-Lapointe M, Pan Y, Shadel GS (2007) Reduced TOR signaling extends chronological life span via increased respiration and upregulation of mitochondrial gene expression. Cell Metab 5: 265–277. 17403371

14. Schroeder EA, Raimundo N, Shadel GS (2013) Epigenetic silencing mediates mitochondria stress-induced longevity. Cell Metab 17: 954–964. doi: 10.1016/j.cmet.2013.04.003 23747251

15. Mirisola MG, Longo VD (2013) A radical signal activates the epigenetic regulation of longevity. Cell Metab 17: 812–813. doi: 10.1016/j.cmet.2013.05.015 23747240

16. Pedruzzi I, Dubouloz F, Cameroni E, Wanke V, Roosen J, et al. (2003) TOR and PKA signaling pathways converge on the protein kinase Rim15 to control entry into G0. Mol Cell 12: 1607–1613. 14690612

17. Talarek N, Cameroni E, Jaquenoud M, Luo X, Bontron S, et al. (2010) Initiation of the TORC1-regulated G0 program requires Igo1/2, which license specific mRNAs to evade degradation via the 5'-3' mRNA decay pathway. Mol Cell 38: 345–355. doi: 10.1016/j.molcel.2010.02.039 20471941

18. Luo X, Talarek N, De Virgilio C (2011) Initiation of the yeast G0 program requires Igo1 and Igo2, which antagonize activation of decapping of specific nutrient-regulated mRNAs. RNA Biol 8: 14–17. 21289492

19. Bontron S, Jaquenoud M, Vaga S, Talarek N, Bodenmiller B, et al. (2013) Yeast endosulfines control entry into quiescence and chronological life span by inhibiting protein phosphatase 2A. Cell Rep 3: 16–22. doi: 10.1016/j.celrep.2012.11.025 23273919

20. Zhang N, Wu J, Oliver SG (2009) Gis1 is required for transcriptional reprogramming of carbon metabolism and the stress response during transition into stationary phase in yeast. Microbiology 155: 1690–1698. doi: 10.1099/mic.0.026377-0 19383711

21. Zhang N, Quan Z, Rash B, Oliver SG (2013) Synergistic effects of TOR and proteasome pathways on the yeast transcriptome and cell growth. Open Biol 3: 120137. doi: 10.1098/rsob.120137 23697803

22. Durchschlag E, Reiter W, Ammerer G, Schuller C (2004) Nuclear localization destabilizes the stress-regulated transcription factor Msn2. J Biol Chem 279: 55425–55432. 15502160

23. Quan Z, Oliver SG, Zhang N (2011) JmjN interacts with JmjC to ensure selective proteolysis of Gis1 by the proteasome. Microbiology 157: 2694–2701. doi: 10.1099/mic.0.048199-0 21680636

24. Zhang N, Oliver SG (2010) The transcription activity of Gis1 is negatively modulated by proteasome-mediated limited proteolysis. J Biol Chem 285: 6465–6476. doi: 10.1074/jbc.M109.073288 20022953

25. Pedruzzi I, Burckert N, Egger P, De Virgilio C (2000) Saccharomyces cerevisiae Ras/cAMP pathway controls post-diauxic shift element-dependent transcription through the zinc finger protein Gis1. EMBO J 19: 2569–2579. 10835355

26. Martinez-Pastor MT, Marchler G, Schuller C, Marchler-Bauer A, Ruis H, et al. (1996) The Saccharomyces cerevisiae zinc finger proteins Msn2p and Msn4p are required for transcriptional induction through the stress response element (STRE). EMBO J 15: 2227–2235. 8641288

27. Hirata Y, Andoh T, Asahara T, Kikuchi A (2003) Yeast glycogen synthase kinase-3 activates Msn2p-dependent transcription of stress responsive genes. Mol Biol Cell 14: 302–312. 12529445

28. Nalley K, Johnston SA, Kodadek T (2006) Proteolytic turnover of the Gal4 transcription factor is not required for function in vivo. Nature 442: 1054–1057. 16929306

29. Lillie SH, Pringle JR (1980) Reserve carbohydrate metabolism in Saccharomyces cerevisiae: responses to nutrient limitation. J Bacteriol 143: 1384–1394. 6997270

30. Murakami C, Delaney JR, Chou A, Carr D, Schleit J, et al. (2012) pH neutralization protects against reduction in replicative lifespan following chronological aging in yeast. Cell Cycle 11: 3087–3096. doi: 10.4161/cc.21465 22871733

31. Li L, Miles S, Melville Z, Prasad A, Bradley G, et al. (2013) Key events during the transition from rapid growth to quiescence in budding yeast require posttranscriptional regulators. Mol Biol Cell 24: 3697–3709. doi: 10.1091/mbc.E13-05-0241 24088570

32. Wolken DM, McInnes J, Pon LA (2014) Aim44p regulates phosphorylation of Hof1p to promote contractile ring closure during cytokinesis in budding yeast. Mol Biol Cell 25: 753–762. doi: 10.1091/mbc.E13-06-0317 24451263

33. Bidlingmaier S, Weiss EL, Seidel C, Drubin DG, Snyder M (2001) The Cbk1p pathway is important for polarized cell growth and cell separation in Saccharomyces cerevisiae. Mol Cell Biol 21: 2449–2462. 11259593

34. Lesage G, Bussey H (2006) Cell wall assembly in Saccharomyces cerevisiae. Microbiol Mol Biol Rev 70: 317–343. 16760306

35. Broek D, Samiy N, Fasano O, Fujiyama A, Tamanoi F, et al. (1985) Differential activation of yeast adenylate cyclase by wild-type and mutant RAS proteins. Cell 41: 763–769. 3891097

36. Marchler G, Schuller C, Adam G, Ruis H (1993) A Saccharomyces cerevisiae UAS element controlled by protein kinase A activates transcription in response to a variety of stress conditions. EMBO J 12: 1997–2003. 8387917

37. Ruiz-Roig C, Vieitez C, Posas F, de Nadal E (2010) The Rpd3L HDAC complex is essential for the heat stress response in yeast. Mol Microbiol 76: 1049–1062. doi: 10.1111/j.1365-2958.2010.07167.x 20398213

38. Ma L, Ho K, Piggott N, Luo Z, Measday V (2012) Interactions between the kinetochore complex and the protein kinase A pathway in Saccharomyces cerevisiae. G3 (Bethesda) 2: 831–841. doi: 10.1534/g3.112.002675 22870406

39. Petitjean A, Hilger F, Tatchell K (1990) Comparison of thermosensitive alleles of the CDC25 gene involved in the cAMP metabolism of Saccharomyces cerevisiae. Genetics 124: 797–806. 2157625

40. Reinders A, Burckert N, Boller T, Wiemken A, De Virgilio C (1998) Saccharomyces cerevisiae cAMP-dependent protein kinase controls entry into stationary phase through the Rim15p protein kinase. Genes Dev 12: 2943–2955. 9744870

41. Lee P, Paik SM, Shin CS, Huh WK, Hahn JS (2011) Regulation of yeast Yak1 kinase by PKA and autophosphorylation-dependent 14-3-3 binding. Mol Microbiol 79: 633–646. doi: 10.1111/j.1365-2958.2010.07471.x 21255108

42. Garrett S, Broach J (1989) Loss of Ras activity in Saccharomyces cerevisiae is suppressed by disruptions of a new kinase gene, YAKI, whose product may act downstream of the cAMP-dependent protein kinase. Genes Dev 3: 1336–1348. 2558053

43. Longo VD (1999) Mutations in signal transduction proteins increase stress resistance and longevity in yeast, nematodes, fruit flies, and mammalian neuronal cells. Neurobiol Aging 20: 479–486. 10638521

44. Francois J, Parrou JL (2001) Reserve carbohydrates metabolism in the yeast Saccharomyces cerevisiae. FEMS Microbiol Rev 25: 125–145. 11152943

45. Allen C, Buttner S, Aragon AD, Thomas JA, Meirelles O, et al. (2006) Isolation of quiescent and nonquiescent cells from yeast stationary-phase cultures. J Cell Biol 174: 89–100. 16818721

46. Li L, Lu Y, Qin LX, Bar-Joseph Z, Werner-Washburne M, et al. (2009) Budding yeast SSD1-V regulates transcript levels of many longevity genes and extends chronological life span in purified quiescent cells. Mol Biol Cell 20: 3851–3864. doi: 10.1091/mbc.E09-04-0347 19570907

47. Laporte D, Lebaudy A, Sahin A, Pinson B, Ceschin J, et al. (2011) Metabolic status rather than cell cycle signals control quiescence entry and exit. J Cell Biol 192: 949–957. doi: 10.1083/jcb.201009028 21402786

48. Swinnen E, Wanke V, Roosen J, Smets B, Dubouloz F, et al. (2006) Rim15 and the crossroads of nutrient signalling pathways in Saccharomyces cerevisiae. Cell Div 1: 3. 16759348

49. Griffioen G, Swinnen S, Thevelein JM (2003) Feedback inhibition on cell wall integrity signaling by Zds1 involves Gsk3 phosphorylation of a cAMP-dependent protein kinase regulatory subunit. J Biol Chem 278: 23460–23471. 12704202

50. Rayner TF, Gray JV, Thorner JW (2002) Direct and novel regulation of cAMP-dependent protein kinase by Mck1p, a yeast glycogen synthase kinase-3. J Biol Chem 277: 16814–16822. 11877433

51. Lee J, Moir RD, McIntosh KB, Willis IM (2012) TOR signaling regulates ribosome and tRNA synthesis via LAMMER/Clk and GSK-3 family kinases. Mol Cell 45: 836–843. doi: 10.1016/j.molcel.2012.01.018 22364741

52. Zimmermann C, Santos A, Gable K, Epstein S, Gururaj C, et al. (2013) TORC1 inhibits GSK3-mediated Elo2 phosphorylation to regulate very long chain fatty acid synthesis and autophagy. Cell Rep 5: 1036–1046. doi: 10.1016/j.celrep.2013.10.024 24239358

53. Zhang HH, Lipovsky AI, Dibble CC, Sahin M, Manning BD (2006) S6K1 regulates GSK3 under conditions of mTOR-dependent feedback inhibition of Akt. Mol Cell 24: 185–197. 17052453

54. Tatchell K, Robinson LC, Breitenbach M (1985) RAS2 of Saccharomyces cerevisiae is required for gluconeogenic growth and proper response to nutrient limitation. Proc Natl Acad Sci U S A 82: 3785–3789. 3889915

55. Fernandez-Banares I, Clotet J, Arino J, Guinovart JJ (1991) Glycogen hyperaccumulation in Saccharomyces cerevisiae ras2 mutant. A biochemical study. FEBS Lett 290: 38–42. 1655535

56. Yang R, Chun KT, Wek RC (1998) Mitochondrial respiratory mutants in yeast inhibit glycogen accumulation by blocking activation of glycogen synthase. J Biol Chem 273: 31337–31344. 9813042

57. Enjalbert B, Parrou JL, Vincent O, Francois J (2000) Mitochondrial respiratory mutants of Saccharomyces cerevisiae accumulate glycogen and readily mobilize it in a glucose-depleted medium. Microbiology 146 (Pt 10): 2685–2694. 11021944

58. McQueen J, van Dyk D, Young B, Loewen C, Measday V (2012) The Mck1 GSK-3 kinase inhibits the activity of Clb2-Cdk1 post-nuclear division. Cell Cycle 11: 3421–3432. doi: 10.4161/cc.21731 22918234

59. Ikui AE, Rossio V, Schroeder L, Yoshida S (2012) A yeast GSK-3 kinase Mck1 promotes Cdc6 degradation to inhibit DNA re-replication. PLoS Genet 8: e1003099. doi: 10.1371/journal.pgen.1003099 23236290

60. Juanes MA, Khoueiry R, Kupka T, Castro A, Mudrak I, et al. (2013) Budding Yeast Greatwall and Endosulfines Control Activity and Spatial Regulation of PP2A(Cdc55) for Timely Mitotic Progression. PLoS Genet 9: e1003575. doi: 10.1371/journal.pgen.1003575 23861665

61. Gharbi-Ayachi A, Labbe JC, Burgess A, Vigneron S, Strub JM, et al. (2010) The substrate of Greatwall kinase, Arpp19, controls mitosis by inhibiting protein phosphatase 2A. Science 330: 1673–1677. doi: 10.1126/science.1197048 21164014

62. Mochida S, Maslen SL, Skehel M, Hunt T (2010) Greatwall phosphorylates an inhibitor of protein phosphatase 2A that is essential for mitosis. Science 330: 1670–1673. doi: 10.1126/science.1195689 21164013

63. Yu J, Fleming SL, Williams B, Williams EV, Li Z, et al. (2004) Greatwall kinase: a nuclear protein required for proper chromosome condensation and mitotic progression in Drosophila. J Cell Biol 164: 487–492. 14970188

64. Rangone H, Wegel E, Gatt MK, Yeung E, Flowers A, et al. (2011) Suppression of scant identifies Endos as a substrate of greatwall kinase and a negative regulator of protein phosphatase 2A in mitosis. PLoS Genet 7: e1002225. doi: 10.1371/journal.pgen.1002225 21852956

65. Fantes PA, Grant WD, Pritchard RH, Sudbery PE, Wheals AE (1975) The regulation of cell size and the control of mitosis. J Theor Biol 50: 213–244. 1127959

66. Johnston GC, Pringle JR, Hartwell LH (1977) Coordination of growth with cell division in the yeast Saccharomyces cerevisiae. Exp Cell Res 105: 79–98. 320023

67. Johnston GC, Singer RA, McFarlane S (1977) Growth and cell division during nitrogen starvation of the yeast Saccharomyces cerevisiae. J Bacteriol 132: 723–730. 334751

68. Johnston GC (1977) Cell size and budding during starvation of the yeast Saccharomyces cerevisiae. J Bacteriol 132: 738–739. 334753

69. Lord PG, Wheals AE (1980) Asymmetrical division of Saccharomyces cerevisiae. J Bacteriol 142: 808–818. 6991494

70. Zhang J, Schneider C, Ottmers L, Rodriguez R, Day A, et al. (2002) Genomic scale mutant hunt identifies cell size homeostasis genes in S. cerevisiae. Curr Biol 12: 1992–2001. 12477387

71. Tu BP, Kudlicki A, Rowicka M, McKnight SL (2005) Logic of the yeast metabolic cycle: temporal compartmentalization of cellular processes. Science 310: 1152–1158. 16254148

72. Muller D, Exler S, Aguilera-Vazquez L, Guerrero-Martin E, Reuss M (2003) Cyclic AMP mediates the cell cycle dynamics of energy metabolism in Saccharomyces cerevisiae. Yeast 20: 351–367. 12627401

73. Futcher B (2006) Metabolic cycle, cell cycle, and the finishing kick to Start. Genome Biol 7: 107. 16677426

74. Sillje HH, Paalman JW, ter Schure EG, Olsthoorn SQ, Verkleij AJ, et al. (1999) Function of trehalose and glycogen in cell cycle progression and cell viability in Saccharomyces cerevisiae. J Bacteriol 181: 396–400. 9882651

75. Miles S, Li L, Davison J, Breeden LL (2013) Xbp1 directs global repression of budding yeast transcription during the transition to quiescence and is important for the longevity and reversibility of the quiescent state. PLoS Genet 9: e1003854. doi: 10.1371/journal.pgen.1003854 24204289

76. Chen G, Bradford WD, Seidel CW, Li R (2012) Hsp90 stress potentiates rapid cellular adaptation through induction of aneuploidy. Nature 482: 246–250. doi: 10.1038/nature10795 22286062

77. Yona AH, Manor YS, Herbst RH, Romano GH, Mitchell A, et al. (2012) Chromosomal duplication is a transient evolutionary solution to stress. Proc Natl Acad Sci U S A 109: 21010–21015. doi: 10.1073/pnas.1211150109 23197825

78. Pavelka N, Rancati G, Zhu J, Bradford WD, Saraf A, et al. (2010) Aneuploidy confers quantitative proteome changes and phenotypic variation in budding yeast. Nature 468: 321–325. doi: 10.1038/nature09529 20962780

79. Gresham D, Desai MM, Tucker CM, Jenq HT, Pai DA, et al. (2008) The repertoire and dynamics of evolutionary adaptations to controlled nutrient-limited environments in yeast. PLoS Genet 4: e1000303. doi: 10.1371/journal.pgen.1000303 19079573

80. Akerlund T, Nordstrom K, Bernander R (1995) Analysis of cell size and DNA content in exponentially growing and stationary-phase batch cultures of Escherichia coli. J Bacteriol 177: 6791–6797. 7592469

81. Goldstein AL, McCusker JH (1999) Three new dominant drug resistance cassettes for gene disruption in Saccharomyces cerevisiae. Yeast 15: 1541–1553. 10514571

82. Longtine MS, McKenzie A 3rd, Demarini DJ, Shah NG, Wach A, et al. (1998) Additional modules for versatile and economical PCR-based gene deletion and modification in Saccharomyces cerevisiae. Yeast 14: 953–961. 9717241

83. Keppler-Ross S, Noffz C, Dean N (2008) A new purple fluorescent color marker for genetic studies in Saccharomyces cerevisiae and Candida albicans. Genetics 179: 705–710. doi: 10.1534/genetics.108.087080 18493083

84. Nagai T, Ibata K, Park ES, Kubota M, Mikoshiba K, et al. (2002) A variant of yellow fluorescent protein with fast and efficient maturation for cell-biological applications. Nat Biotechnol 20: 87–90. 11753368

85. Parrou JL, Francois J (1997) A simplified procedure for a rapid and reliable assay of both glycogen and trehalose in whole yeast cells. Anal Biochem 248: 186–188. 9177741

86. Ocampo A, Barrientos A (2011) Quick and reliable assessment of chronological life span in yeast cell populations by flow cytometry. Mech Ageing Dev 132: 315–323. doi: 10.1016/j.mad.2011.06.007 21736893

87. Vokes MS, Carpenter AE (2008) Using CellProfiler for automatic identification and measurement of biological objects in images. Curr Protoc Mol Biol Chapter 14: Unit 14 17.

88. Haase SB, Reed SI (2002) Improved flow cytometric analysis of the budding yeast cell cycle. Cell Cycle 1: 132–136. 12429922

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