The coordinate actions of calcineurin and Hog1 mediate the stress response through multiple nodes of the cell cycle network
Autoři:
Cassandra M. Leech aff001; Mackenzie J. Flynn aff001; Heather E. Arsenault aff001; Jianhong Ou aff001; Haibo Liu aff001; Lihua Julie Zhu aff001; Jennifer A. Benanti aff001
Působiště autorů:
Department of Molecular, Cell and Cancer Biology, University of Massachusetts Medical School, Worcester, Massachusetts, United States of America
aff001; Program in Bioinformatics and Integrative Biology, Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts, United States of America
aff002
Vyšlo v časopise:
The coordinate actions of calcineurin and Hog1 mediate the stress response through multiple nodes of the cell cycle network. PLoS Genet 16(4): e32767. doi:10.1371/journal.pgen.1008600
Kategorie:
Research Article
doi:
https://doi.org/10.1371/journal.pgen.1008600
Souhrn
Upon exposure to environmental stressors, cells transiently arrest the cell cycle while they adapt and restore homeostasis. A challenge for all cells is to distinguish between stress signals and coordinate the appropriate adaptive response with cell cycle arrest. Here we investigate the role of the phosphatase calcineurin (CN) in the stress response and demonstrate that CN activates the Hog1/p38 pathway in both yeast and human cells. In yeast, the MAPK Hog1 is transiently activated in response to several well-studied osmostressors. We show that when a stressor simultaneously activates CN and Hog1, CN disrupts Hog1-stimulated negative feedback to prolong Hog1 activation and the period of cell cycle arrest. Regulation of Hog1 by CN also contributes to inactivation of multiple cell cycle-regulatory transcription factors (TFs) and the decreased expression of cell cycle-regulated genes. CN-dependent downregulation of G1/S genes is dependent upon Hog1 activation, whereas CN inactivates G2/M TFs through a combination of Hog1-dependent and -independent mechanisms. These findings demonstrate that CN and Hog1 act in a coordinated manner to inhibit multiple nodes of the cell cycle-regulatory network. Our results suggest that crosstalk between CN and stress-activated MAPKs helps cells tailor their adaptive responses to specific stressors.
Klíčová slova:
Cell cycle and cell division – Cell cycle inhibitors – Cellular stress responses – Gene expression – Gene regulation – Phosphorylation – Synthesis phase – Cellular crosstalk
Zdroje
1. Ho Y-H, Gasch AP. Exploiting the yeast stress-activated signaling network to inform on stress biology and disease signaling. Curr Genet. Springer Berlin Heidelberg; 2015 Nov;61(4):503–11. doi: 10.1007/s00294-015-0491-0 25957506
2. Haase SB, Wittenberg C. Topology and Control of the Cell-Cycle-Regulated Transcriptional Circuitry. Genetics. 2014 Jan 6;196(1):65–90. doi: 10.1534/genetics.113.152595 24395825
3. Sadasivam S, DeCaprio JA. The DREAM complex: master coordinator of cell cycle-dependent gene expression. Nat Rev Cancer. 2013 Aug;13(8):585–95. doi: 10.1038/nrc3556 23842645
4. Bertoli C, Skotheim JM, de Bruin RAM. Control of cell cycle transcription during G1 and S phases. Nat Rev Mol Cell Biol. Nature Publishing Group; 2013 Aug 1;14(8):518–28. doi: 10.1038/nrm3629 23877564
5. Morgan DO. The Cell Cycle. New Science Press; 2007. 1 p.
6. Medina DL, Di Paola S, Peluso I, Armani A, De Stefani D, Venditti R, et al. Lysosomal calcium signalling regulates autophagy through calcineurin and TFEB. Nat Cell Biol. Nature Publishing Group; 2015 Mar;17(3):288–99. doi: 10.1038/ncb3114 25720963
7. Zhang X, Cheng X, Yu L, Yang J, Calvo R, Patnaik S, et al. MCOLN1 is a ROS sensor in lysosomes that regulates autophagy. Nature Communications. Nature Publishing Group; 2016 Jun 30;7(1):12109.
8. Cyert MS, Philpott CC. Regulation of cation balance in Saccharomyces cerevisiae. Genetics. 2013 Mar;193(3):677–713. doi: 10.1534/genetics.112.147207 23463800
9. Yoshimoto H, Saltsman K, Gasch AP, Li HX, Ogawa N, Botstein D, et al. Genome-wide analysis of gene expression regulated by the calcineurin/Crz1p signaling pathway in Saccharomyces cerevisiae. J Biol Chem. 2002 Aug 23;277(34):31079–88. doi: 10.1074/jbc.M202718200 12058033
10. Goldman A, Roy J, Bodenmiller B, Wanka S, Landry CR, Aebersold R, et al. The Calcineurin Signaling Network Evolves via Conserved Kinase-Phosphatase Modules that Transcend Substrate Identity. Mol Cell. 2014 Jun 11.
11. Mizunuma M, Hirata D, Miyaoka R, Miyakawa T. GSK-3 kinase Mck1 and calcineurin coordinately mediate Hsl1 down-regulation by Ca2+ in budding yeast. EMBO J. 2001 Mar 1;20(5):1074–85. doi: 10.1093/emboj/20.5.1074 11230131
12. Arsenault HE, Roy J, Mapa CE, Cyert MS, Benanti JA. Hcm1 integrates signals from Cdk1 and Calcineurin to control cell proliferation. Mol Biol Cell [Internet]. 2015 Oct 13;26(20):3570–7. Available from: http://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&id=26269584&retmode=ref&cmd=prlinks doi: 10.1091/mbc.E15-07-0469 26269584
13. Bellí G, Gari E, Aldea M, Herrero E. Osmotic stress causes a G1 cell cycle delay and downregulation of Cln3/Cdc28 activity in Saccharomyces cerevisiae. Mol Microbiol. 2001 Feb;39(4):1022–35. doi: 10.1046/j.1365-2958.2001.02297.x 11251821
14. González-Novo A, Jiménez J, Clotet J, Nadal-Ribelles M, Cavero S, de Nadal E, et al. Hog1 targets Whi5 and Msa1 transcription factors to downregulate cyclin expression upon stress. Mol Cell Biol. American Society for Microbiology; 2015 May;35(9):1606–18. doi: 10.1128/MCB.01279-14 25733686
15. Mizunuma M, Hirata D, Miyahara K, Tsuchiya E, Miyakawa T. Role of calcineurin and Mpk1 in regulating the onset of mitosis in budding yeast. Nature. 1998 Mar 19;392(6673):303–6. doi: 10.1038/32695 9521328
16. Yokoyama H, Mizunuma M, Okamoto M, Yamamoto J, Hirata D, Miyakawa T. Involvement of calcineurin-dependent degradation of Yap1p in Ca2+-induced G2 cell-cycle regulation in Saccharomyces cerevisiae. EMBO Rep. 2006 Feb 17.
17. Ferrezuelo F, Colomina N, Futcher B, Aldea M. The transcriptional network activated by Cln3 cyclin at the G1-to-S transition of the yeast cell cycle. Genome Biol. 2010;11(6):R67. doi: 10.1186/gb-2010-11-6-r67 20573214
18. Spellman PT, Sherlock G, Zhang MQ, Iyer VR, Anders K, Eisen MB, et al. Comprehensive identification of cell cycle-regulated genes of the yeast Saccharomyces cerevisiae by microarray hybridization. Mol Biol Cell. 1998 Dec 1;9(12):3273–97. doi: 10.1091/mbc.9.12.3273 9843569
19. Hu B, Petela N, Kurze A, Chan K-L, Chapard C, Nasmyth K. Biological chromodynamics: a general method for measuring protein occupancy across the genome by calibrating ChIP-seq. Nucleic Acids Res. 2015 Jun 30;:gkv670.
20. Macisaac KD, Wang T, Gordon DB, Gifford DK, Stormo GD, Fraenkel E. An improved map of conserved regulatory sites for Saccharomyces cerevisiae. BMC Bioinformatics. 2006;7:113. doi: 10.1186/1471-2105-7-113 16522208
21. Venters BJ, Wachi S, Mavrich TN, Andersen BE, Jena P, Sinnamon AJ, et al. A comprehensive genomic binding map of gene and chromatin regulatory proteins in Saccharomyces. Mol Cell. 2011 Feb 18;41(4):480–92. doi: 10.1016/j.molcel.2011.01.015 21329885
22. Chang Y-L, Tseng S-F, Huang Y-C, Shen Z-J, Hsu P-H, Hsieh M-H, et al. Yeast Cip1 is activated by environmental stress to inhibit Cdk1–G1 cyclins via Mcm1 and Msn2/4. Nature Communications. Springer US; 2017 Jun 22;8(1):1–13. doi: 10.1038/s41467-016-0009-6
23. Escoté X, Zapater M, Clotet J, Posas F. Hog1 mediates cell-cycle arrest in G1 phase by the dual targeting of Sic1. Nat Cell Biol. 2004 Oct;6(10):997–1002. doi: 10.1038/ncb1174 15448699
24. Matsumoto TK, Ellsmore AJ, Cessna SG, Low PS, Pardo JM, Bressan RA, et al. An osmotically induced cytosolic Ca2+ transient activates calcineurin signaling to mediate ion homeostasis and salt tolerance of Saccharomyces cerevisiae. J Biol Chem. 2002 Sep 6;277(36):33075–80. doi: 10.1074/jbc.M205037200 12084723
25. Capaldi AP, Kaplan T, Liu Y, Habib N, Regev A, Friedman N, et al. Structure and function of a transcriptional network activated by the MAPK Hog1. Nat Genet. 2008 Nov;40(11):1300–6. doi: 10.1038/ng.235 18931682
26. Brewster JL, de Valoir T, Dwyer ND, Winter E, Gustin MC. An osmosensing signal transduction pathway in yeast. Science. 1993 Mar 19;259(5102):1760–3. doi: 10.1126/science.7681220 7681220
27. Stathopoulos-Gerontides A, Guo JJ, Cyert MS. Yeast calcineurin regulates nuclear localization of the Crz1p transcription factor through dephosphorylation. Genes & Development. 1999 Apr 1;13(7):798–803.
28. Benanti JA, Galloway DA. Normal human fibroblasts are resistant to RAS-induced senescence. Mol Cell Biol. 2004 Apr;24(7):2842–52. doi: 10.1128/MCB.24.7.2842-2852.2004 15024073
29. Hao N, Zeng Y, Elston TC, Dohlman HG. Control of MAPK specificity by feedback phosphorylation of shared adaptor protein Ste50. J Biol Chem. 2008 Dec 5;283(49):33798–802. doi: 10.1074/jbc.C800179200 18854322
30. Hao N, Behar M, Parnell SC, Torres MP, Borchers CH, Elston TC, et al. A systems-biology analysis of feedback inhibition in the Sho1 osmotic-stress-response pathway. Current Biology. 2007 Apr 17;17(8):659–67. doi: 10.1016/j.cub.2007.02.044 17363249
31. Lee J, Reiter W, Dohnal I, Gregori C, Beese-Sims S, Kuchler K, et al. MAPK Hog1 closes the S. cerevisiae glycerol channel Fps1 by phosphorylating and displacing its positive regulators. Genes & Development. Cold Spring Harbor Lab; 2013 Dec 1;27(23):2590–601.
32. Dihazi H, Kessler R, Eschrich K. High osmolarity glycerol (HOG) pathway-induced phosphorylation and activation of 6-phosphofructo-2-kinase are essential for glycerol accumulation and yeast cell proliferation under hyperosmotic stress. J Biol Chem. American Society for Biochemistry and Molecular Biology; 2004 Jun 4;279(23):23961–8. doi: 10.1074/jbc.M312974200 15037628
33. Mettetal JT, Muzzey D, Gómez-Uribe C, van Oudenaarden A. The frequency dependence of osmo-adaptation in Saccharomyces cerevisiae. Science. American Association for the Advancement of Science; 2008 Jan 25;319(5862):482–4.
34. Westfall PJ, Patterson JC, Chen RE, Thorner J. Stress resistance and signal fidelity independent of nuclear MAPK function. Proceedings of the National Academy of Sciences. National Academy of Sciences; 2008 Aug 26;105(34):12212–7.
35. Maeda T, Wurgler-Murphy SM, Saito H. A two-component system that regulates an osmosensing MAP kinase cascade in yeast. Nature. Nature Publishing Group; 1994 May 19;369(6477):242–5. doi: 10.1038/369242a0 8183345
36. Horak CE, Luscombe NM, Qian J, Bertone P, Piccirrillo S, Gerstein M, et al. Complex transcriptional circuitry at the G1/S transition in Saccharomyces cerevisiae. Genes & Development. 2002 Dec 1;16(23):3017–33.
37. Orlando DA, Lin CY, Bernard A, Wang JY, Socolar JES, Iversen ES, et al. Global control of cell-cycle transcription by coupled CDK and network oscillators. Nature. 2008 Jun 12;453(7197):944–7. doi: 10.1038/nature06955 18463633
38. Pramila T, Wu W, Miles S, Noble WS, Breeden LL. The Forkhead transcription factor Hcm1 regulates chromosome segregation genes and fills the S-phase gap in the transcriptional circuitry of the cell cycle. Genes & Development. 2006 Aug 15;20(16):2266–78.
39. Pic-Taylor A, Darieva Z, Morgan BA, Sharrocks AD. Regulation of Cell Cycle-Specific Gene Expression through Cyclin-Dependent Kinase-Mediated Phosphorylation of the Forkhead Transcription Factor Fkh2p. Mol Cell Biol. 2004 Oct 27;24(22):10036–46. doi: 10.1128/MCB.24.22.10036-10046.2004 15509804
40. Reynolds D. Recruitment of Thr 319-phosphorylated Ndd1p to the FHA domain of Fkh2p requires Clbkinase activity: a mechanism for CLB cluster gene activation. Genes & Development. 2003 Jul 15;17(14):1789–802.
41. Darieva Z, Pic-Taylor A, Boros J, Spanos A, Geymonat M, Reece RJ, et al. Cell cycle-regulated transcription through the FHA domain of Fkh2p and the coactivator Ndd1p. Current Biology. 2003 Sep 30;13(19):1740–5. doi: 10.1016/j.cub.2003.08.053 14521842
42. Clotet J, Escoté X, Adrover MA, Yaakov G, Garí E, Aldea M, et al. Phosphorylation of Hsl1 by Hog1 leads to a G2 arrest essential for cell survival at high osmolarity. EMBO J. 2006 Jun 7;25(11):2338–46. doi: 10.1038/sj.emboj.7601095 16688223
43. Kellogg DR. Wee1-dependent mechanisms required for coordination of cell growth and cell division. J Cell Sci. The Company of Biologists Ltd; 2003 Dec 15;116(Pt 24):4883–90. doi: 10.1242/jcs.00908 14625382
44. Muzzey D, Gómez-Uribe CA, Mettetal JT, van Oudenaarden A. A systems-level analysis of perfect adaptation in yeast osmoregulation. Cell. 2009 Jul 10;138(1):160–71. doi: 10.1016/j.cell.2009.04.047 19596242
45. English JG, Shellhammer JP, Malahe M, McCarter PC, Elston TC, Dohlman HG. MAPK feedback encodes a switch and timer for tunable stress adaptation in yeast. Sci Signal. American Association for the Advancement of Science; 2015 Jan 13;8(359):ra5–ra5.
46. Shitamukai A, Hirata D, Sonobe S, Miyakawa T. Evidence for antagonistic regulation of cell growth by the calcineurin and high osmolarity glycerol pathways in Saccharomyces cerevisiae. J Biol Chem. 2004 Jan 30;279(5):3651–61. doi: 10.1074/jbc.M306098200 14583627
47. Gasch AP, Spellman PT, Kao CM, Carmel-Harel O, Eisen MB, Storz G, et al. Genomic expression programs in the response of yeast cells to environmental changes. Mol Biol Cell. 2000 Dec;11(12):4241–57. doi: 10.1091/mbc.11.12.4241 11102521
48. Winkler A, Arkind C, Mattison CP, Burkholder A, Knoche K, Ota I. Heat stress activates the yeast high-osmolarity glycerol mitogen-activated protein kinase pathway, and protein tyrosine phosphatases are essential under heat stress. Eukaryotic Cell. 2002 Apr;1(2):163–73. doi: 10.1128/EC.1.2.163-173.2002 12455951
49. Piao H, MacLean Freed J, Mayinger P. Metabolic activation of the HOG MAP kinase pathway by Snf1/AMPK regulates lipid signaling at the Golgi. Traffic. John Wiley & Sons, Ltd (10.1111); 2012 Nov;13(11):1522–31. doi: 10.1111/j.1600-0854.2012.01406.x 22882253
50. Sotelo J, Rodríguez-Gabriel MA. Mitogen-activated protein kinase Hog1 is essential for the response to arsenite in Saccharomyces cerevisiae. Eukaryotic Cell. American Society for Microbiology Journals; 2006 Oct;5(10):1826–30. doi: 10.1128/EC.00225-06 16920868
51. Thorsen M, Di Y, Tängemo C, Morillas M, Ahmadpour D, Van der Does C, et al. The MAPK Hog1p modulates Fps1p-dependent arsenite uptake and tolerance in yeast. Boone C, editor. Mol Biol Cell. 2006 Oct;17(10):4400–10. doi: 10.1091/mbc.E06-04-0315 16885417
52. de Nadal E, Alepuz PM, Posas F. Dealing with osmostress through MAP kinase activation. EMBO Rep. EMBO Press; 2002 Aug;3(8):735–40. doi: 10.1093/embo-reports/kvf158 12151331
53. Ono K, Han J. The p38 signal transduction pathway: activation and function. Cell Signal. 2000 Jan;12(1):1–13. doi: 10.1016/s0898-6568(99)00071-6 10676842
54. Levin DE. Regulation of cell wall biogenesis in Saccharomyces cerevisiae: the cell wall integrity signaling pathway. Genetics. 2011 Dec;189(4):1145–75. doi: 10.1534/genetics.111.128264 22174182
55. Farcasanu IC, Hirata D, Tsuchiya E, Nishiyama F, Miyakawa T. Protein phosphatase 2B of Saccharomyces cerevisiae is required for tolerance to manganese, in blocking the entry of ions into the cells. Eur J Biochem. 1995 Sep 15;232(3):712–7. 7588708
56. Hogan PG, Chen L, Nardone J, Rao A. Transcriptional regulation by calcium, calcineurin, and NFAT. Genes & Development. 2003 Sep 15;17(18):2205–32.
57. Vaeth M, Feske S. NFAT control of immune function: New Frontiers for an Abiding Trooper. F1000Res. 2018 Mar 2;7:260–13. doi: 10.12688/f1000research.13426.1 29568499
58. Gubern A, Joaquin M, Marquès M, Maseres P, Garcia-Garcia J, Amat R, et al. The N-Terminal Phosphorylation of RB by p38 Bypasses Its Inactivation by CDKs and Prevents Proliferation in Cancer Cells. Mol Cell. 2016 Oct 6;64(1):25–36. doi: 10.1016/j.molcel.2016.08.015 27642049
59. Longtine MS, McKenzie A, Demarini DJ, Shah NG, Wach A, Brachat A, et al. Additional modules for versatile and economical PCR-based gene deletion and modification in Saccharomyces cerevisiae. Yeast. John Wiley & Sons, Ltd; 1998 Jul;14(10):953–61. doi: 10.1002/(SICI)1097-0061(199807)14:10<953::AID-YEA293>3.0.CO;2-U 9717241
60. Rothstein R. Targeting, disruption, replacement, and allele rescue: integrative DNA transformation in yeast. Meth Enzymol. 1991;194:281–301. doi: 10.1016/0076-6879(91)94022-5 2005793
61. Benanti JA, Cheung SK, Brady MC, Toczyski DP. A proteomic screen reveals SCFGrr1 targets that regulate the glycolytic-gluconeogenic switch. Nat Cell Biol. 2007 Oct;9(10):1184–91. doi: 10.1038/ncb1639 17828247
62. Landry BD, Doyle JP, Toczyski DP, Benanti JA. F-Box Protein Specificity for G1 Cyclins Is Dictated by Subcellular Localization. PLoS Genet. 2012 Jul 26;8(7):e1002851. doi: 10.1371/journal.pgen.1002851 22844257
63. Schmitt ME, Brown TA, Trumpower BL. A rapid and simple method for preparation of RNA from Saccharomyces cerevisiae. Nucleic Acids Res. 1990 May 25;18(10):3091–2. doi: 10.1093/nar/18.10.3091 2190191
64. Kim D, Pertea G, Trapnell C, Pimentel H, Kelley R, Salzberg SL. TopHat2: accurate alignment of transcriptomes in the presence of insertions, deletions and gene fusions. Genome Biol. BioMed Central; 2013 Apr 25;14(4):R36. doi: 10.1186/gb-2013-14-4-r36 23618408
65. Anders S, Pyl PT, Huber W. HTSeq—a Python framework to work with high-throughput sequencing data. Bioinformatics. 2015 Jan 15;31(2):166–9. doi: 10.1093/bioinformatics/btu638 25260700
66. Law CW, Chen Y, Shi W, Smyth GK. voom: Precision weights unlock linear model analysis tools for RNA-seq read counts. Genome Biol. BioMed Central; 2014 Feb 3;15(2):R29. doi: 10.1186/gb-2014-15-2-r29 24485249
67. Benjamini Y, Hochberg Y. Controlling the False Discovery Rate: A Practical and Powerful Approach to Multiple Testing. Journal of the Royal Statistical Society: Series B (Methodological). John Wiley & Sons, Ltd (10.1111); 1995;57(1):289–300.
68. Minas C, Waddell SJ, Montana G. Distance-based differential analysis of gene curves. Bioinformatics. 2011 Nov 15;27(22):3135–41. doi: 10.1093/bioinformatics/btr528 21984759
69. Marceau AH, Brison CM, Nerli S, Arsenault HE, McShan AC, Chen E, et al. An order-to-disorder structural switch activates the FoxM1 transcription factor. Elife. 2019 May 28;8:620.
70. Willis N, Rhind N. Mus81, Rhp51(Rad51), and Rqh1 Form an Epistatic Pathway Required for the S-Phase DNA Damage Checkpoint. Mol Biol Cell. American Society for Cell Biology; 2009 Feb 1;20(3):819–33. doi: 10.1091/mbc.E08-08-0798 19037101
Článek vyšel v časopise
PLOS Genetics
2020 Číslo 4
- Prof. Libor Grubhoffer: Nová varianta mpox je příležitostí pokročit v poznání původce varioly
- Co obsahují nové pokyny WHO pro dozor nad antibiotickou rezistencí?
- AI místo lékaře? Výzkum zkoumal ochotu Čechů konzultovat své zdraví s umělou inteligencí
- Prof. Jan Škrha: Metformin je bezpečný, ale je třeba jej bezpečně užívat a léčbu kontrolovat
- Ibuprofen jako alternativa antibiotik při léčbě infekcí močových cest
Nejčtenější v tomto čísle
- Analysis of genes within the schizophrenia-linked 22q11.2 deletion identifies interaction of night owl/LZTR1 and NF1 in GABAergic sleep control
- High expression in maize pollen correlates with genetic contributions to pollen fitness as well as with coordinated transcription from neighboring transposable elements
- Molecular genetics of maternally-controlled cell divisions
- Spastin mutations impair coordination between lipid droplet dispersion and reticulum