Skip to main content
SpringerLink
Log in

Exploiting the yeast stress-activated signaling network to inform on stress biology and disease signaling

  • Review
  • Published:
Current Genetics Aims and scope Submit manuscript

Abstract

Healthy cells utilize intricate systems to monitor their environment and mount robust responses in the event of cellular stress. Whether stress arises from external insults or defects due to mutation and disease, cells must be able to respond precisely to mount the appropriate defenses. Multi-faceted stress responses are generally coupled with arrest of growth and cell-cycle progression, which both limits the transmission of damaged materials and serves to reallocate limited cellular resources toward defense. Therefore, stress defense versus rapid growth represent competing interests in the cell. How eukaryotic cells set the balance between defense versus proliferation, and in particular knowledge of the regulatory networks that control this decision, are poorly understood. In this perspective, we expand upon our recent work inferring the stress-activated signaling network in budding yeast, which captures pathways controlling stress defense and regulators of growth and cell-cycle progression. We highlight similarities between the yeast and mammalian stress responses and explore how stress-activated signaling networks in yeast can inform on signaling defects in human cancers.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  • Abraham RT (2001) Cell cycle checkpoint signaling through the ATM and ATR kinases. Genes Dev 15:2177–2196

    Article  CAS  PubMed  Google Scholar 

  • Akeno N, Miller AL, Ma X, Wikenheiser-Brokamp KA (2015) p53 suppresses carcinoma progression by inhibiting mTOR pathway activation. Oncogene 34:589–599

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Albertyn J, Hohmann S, Thevelein JM, Prior BA (1994) GPD1, which encodes glycerol-3-phosphate dehydrogenase, is essential for growth under osmotic stress in Saccharomyces cerevisiae, and its expression is regulated by the high-osmolarity glycerol response pathway. Mol Cell Biol 14:4135–4144

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Arava Y, Wang Y, Storey JD, Liu CL, Brown PO, Herschlag D (2003) Genome-wide analysis of mRNA translation profiles in Saccharomyces cerevisiae. Proc Natl Acad Sci USA 100:3889–3894

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Ashwell JD (2006) The many paths to p38 mitogen-activated protein kinase activation in the immune system. Nat Rev Immunol 6:532–540

    Article  CAS  PubMed  Google Scholar 

  • Beck T, Hall MN (1999) The TOR signalling pathway controls nuclear localization of nutrient-regulated transcription factors. Nature 402:689–692

    Article  CAS  PubMed  Google Scholar 

  • Beckerman R, Prives C (2010) Transcriptional regulation by p53. Cold Spring Harb Perspect Biol 2:a000935

    Article  PubMed Central  PubMed  Google Scholar 

  • Bellí G, Garí E, Aldea M, Herrero E (2001) Osmotic stress causes a G1 cell cycle delay and downregulation of Cln3/Cdc28 activity in Saccharomyces cerevisiae. Mol Microbiol 39:1022–1035

    Article  PubMed  Google Scholar 

  • Berry DB, Gasch AP (2008) Stress-activated genomic expression changes serve a preparative role for impending stress in yeast. Mol Biol Cell 19:4580–4587

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Berry DB, Guan Q, Hose J, Haroon S, Gebbia M, Heisler LE, Nislow C, Giaever G, Gasch AP (2011) Multiple means to the same end: the genetic basis of acquired stress resistance in yeast. PLoS Genet 7:e1002353

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Brauer MJ, Huttenhower C, Airoldi EM, Rosenstein R, Matese JC, Gresham D, Boer VM, Troyanskaya OG, Botstein D (2008) Coordination of growth rate, cell cycle, stress response, and metabolic activity in yeast. Mol Biol Cell 19:352–367

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Broach JR (2012) Nutritional control of growth and development in yeast. Genetics 192:73–105

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Budde A, Grummt I (1999) p53 represses ribosomal gene transcription. Oncogene 18:1119–1124

    Article  CAS  PubMed  Google Scholar 

  • Cairns CA, White RJ (1998) p53 is a general repressor of RNA polymerase III transcription. EMBO J 17:3112–3123

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Castrillo JI, Zeef LA, Hoyle DC, Zhang N, Hayes A, Gardner DC, Cornell MJ, Petty J, Hakes L, Wardleworth L, Rash B, Brown M, Dunn WB, Broadhurst D, O’Donoghue K, Hester SS, Dunkley TP, Hart SR, Swainston N, Li P, Gaskell SJ, Paton NW, Lilley KS, Kell DB, Oliver SG (2007) Growth control of the eukaryote cell: a systems biology study in yeast. J Biol 6:4

    Article  PubMed Central  PubMed  Google Scholar 

  • Causton HC, Ren B, Koh SS, Harbison CT, Kanin E, Jennings EG, Lee TI, True HL, Lander ES, Young RA (2001) Remodeling of yeast genome expression in response to environmental changes. Mol Biol Cell 12:323–337

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Chasman D, Ho Y-H, Berry DB, Nemec CM, MacGilvray ME, Hose J, Merrill AE, Lee MV, Will JL, Coon JJ, Ansari AZ, Craven M, Gasch AP (2014) Pathway connectivity and signaling coordination in the yeast stress-activated signaling network. Mol Syst Biol 19:759

    Article  CAS  Google Scholar 

  • Chatr-Aryamontri A, Breitkreutz BJ, Oughtred R, Boucher L, Heinicke S, Chen D, Stark C, Breitkreutz A, Kolas N, O’Donnell L, Reguly T, Nixon J, Ramage L, Winter A, Sellam A, Chang C, Hirschman J, Theesfeld C, Rust J, Livstone MS, Dolinski K, Tyers M (2015) The BioGRID interaction database: 2015 update. Nucleic Acids Res 43:D470–D478

    Article  PubMed Central  PubMed  Google Scholar 

  • Chauvin C, Koka V, Nouschi A, Mieulet V, Hoareau-Aveilla C, Dreazen A, Cagnard N, Carpentier W, Kiss T, Meyuhas O, Pende M (2014) Ribosomal protein S6 kinase activity controls the ribosome biogenesis transcriptional program. Oncogene 33:474–483

    Article  CAS  PubMed  Google Scholar 

  • Claypool JA, French SL, Johzuka K, Eliason K, Vu L, Dodd JA, Beyer AL, Nomura M (2004) Tor pathway regulates Rrn3p-dependent recruitment of yeast RNA polymerase I to the promoter but does not participate in alteration of the number of active genes. Mol Biol Cell 15:946–956

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Clotet J, Escote X, Adrover MA, Yaakov G, Gari E, Aldea M, de Nadal E, Posas F (2006) Phosphorylation of Hsl1 by Hog1 leads to a G2 arrest essential for cell survival at high osmolarity. EMBO J 25:2338–2346

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Conrad M, Schothorst J, Kankipati HN, Van Zeebroeck G, Rubio-Texeira M, Thevelein JM (2014) Nutrient sensing and signaling in the yeast Saccharomyces cerevisiae. FEMS Microbiol Rev 38:254–299

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Cook KE, O’Shea EK (2012) Hog1 controls global reallocation of RNA Pol II upon osmotic shock in Saccharomyces cerevisiae. G3 (Bethesda) 2:1129–1136

    Article  CAS  Google Scholar 

  • Deluca TF, Wu IH, Pu J, Monaghan T, Peshkin L, Singh S, Wall DP (2006) Roundup: a multi-genome repository of orthologs and evolutionary distances. Bioinformatics 22:2044–2046

    Article  CAS  PubMed  Google Scholar 

  • Drosten M, Sum EY, Lechuga CG, Simón-Carrasco L, Jacob HK, García-Medina R, Huang S, Beijersbergen RL, Bernards R, Barbacid M (2014) Loss of p53 induces cell proliferation via Ras-independent activation of the Raf/Mek/Erk signaling pathway. Proc Natl Acad Sci USA 111:15155–15160

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Elliott B, Futcher B (1993) Stress resistance of yeast cells is largely independent of cell cycle phase. Yeast 9:33–42

    Article  CAS  PubMed  Google Scholar 

  • Escoté X, Zapater M, Clotet J, Posas F (2004) Hog1 mediates cell-cycle arrest in G1 phase by the dual targeting of Sic1. Nat Cell Biol 6:997–1002

    Article  PubMed  CAS  Google Scholar 

  • Feng Z, Levine AJ (2010) The regulation of energy metabolism and the IGF-1/mTOR pathways by the p53 protein. Trends Cell Biol 20:427–434

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Fernández-Medarde A, Santos E (2011) Ras in cancer and developmental diseases. Genes Cancer 2:344–358

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Forbes SA, Beare D, Gunasekaran P, Leung K, Bindal N, Boutselakis H, Ding M, Bamford S, Cole C, Ward S, Kok CY, Jia M, De T, Teague JW, Stratton MR, McDermott U, Campbell PJ (2015) COSMIC: exploring the world’s knowledge of somatic mutations in human cancer. Nucleic Acids Res 43:D805–D811

    Article  PubMed Central  PubMed  Google Scholar 

  • Friedman N (2004) Inferring cellular networks using probabilistic graphical models. Science 303:799–805

    Article  CAS  PubMed  Google Scholar 

  • Gambino V, De Michele G, Venezia O, Migliaccio P, Dall’Olio V, Bernard L, Minardi SP, Della Fazia MA, Bartoli D, Servillo G, Alcalay M, Luzi L, Giorgio M, Scrable H, Pelicci PG, Migliaccio E (2013) Oxidative stress activates a specific p53 transcriptional response that regulates cellular senescence and aging. Aging Cell 12:435–445

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Gasch AP (2002) The environmental stress response: a common yeast response to environmental stresses. Springer-Verlag, Heidelberg

    Google Scholar 

  • Gasch AP, Spellman PT, Kao CM, Carmel-Harel O, Eisen MB, Storz G, Botstein D, Brown PO (2000) Genomic expression programs in the response of yeast cells to environmental changes. Mol Biol Cell 11:4241–4257

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Gat-Viks I, Shamir R (2007) Refinement and expansion of signaling pathways: the osmotic response network in yeast. Genome Res 17:358–367

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Gingras AC, Kennedy SG, O’Leary MA, Sonenberg N, Hay N (1998) 4E-BP1, a repressor of mRNA translation, is phosphorylated and inactivated by the Akt(PKB) signaling pathway. Genes Dev 12:502–513

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Gitter A, Carmi M, Barkai N, Bar-Joseph Z (2013) Linking the signaling cascades and dynamic regulatory networks controlling stress responses. Genome Res 23:265–276

    Article  CAS  Google Scholar 

  • Görner W, Durchschlag E, Martinez-Pastor MT, Estruch F, Ammerer G, Hamilton B, Ruis H, Schüller C (1998) Nuclear localization of the C2H2 zinc finger protein Msn2p is regulated by stress and protein kinase A activity. Genes Dev 12:586–597

    Article  PubMed Central  PubMed  Google Scholar 

  • Hannan KM, Sanij E, Hein N, Hannan RD, Pearson RB (2011) Signaling to the ribosome in cancer––It is more than just mTORC1. IUBMB Life 63:79–85

    Article  CAS  PubMed  Google Scholar 

  • Hasty P, Sharp ZD, Curiel TJ, Campisi J (2013) mTORC1 and p53: clash of the gods? Cell Cycle 12:20–25

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Heinisch JJ, Lorberg A, Schmitz HP, Jacoby JJ (1999) The protein kinase C-mediated MAP kinase pathway involved in the maintenance of cellular integrity in Saccharomyces cerevisiae. Mol Microbiol 32:671–680

    Article  CAS  PubMed  Google Scholar 

  • Huarte M, Guttman M, Feldser D, Garber M, Koziol MJ, Kenzelmann-Broz D, Khalil AM, Zuk O, Amit I, Rabani M, Attardi LD, Regev A, Lander ES, Jacks T, Rinn JL (2010) A large intergenic noncoding RNA induced by p53 mediates global gene repression in the p53 response. Cell 142:409–419

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Huber A, French SL, Tekotte H, Yerlikaya S, Stahl M, Perepelkina MP, Tyers M, Rougemont J, Beyer AL, Loewith R (2011) Sch9 regulates ribosome biogenesis via Stb3, Dot6 and Tod6 and the histone deacetylase complex RPD3L. EMBO J 30:3052–3064

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Jones RG, Thompson CB (2009) Tumor suppressors and cell metabolism: a recipe for cancer growth. Genes Dev 23:537–548

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Jorgensen P, Nishikawa JL, Breitkreutz BJ, Tyers M (2002) Systematic identification of pathways that couple cell growth and division in yeast. Science 297:395–400

    Article  CAS  PubMed  Google Scholar 

  • Jorgensen P, Rupes I, Sharom JR, Schneper L, Broach JR, Tyers M (2004) A dynamic transcriptional network communicates growth potential to ribosome synthesis and critical cell size. Genes Dev 18:2491–2505

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Kantidakis T, Ramsbottom BA, Birch JL, Dowding SN, White RJ (2010) mTOR associates with TFIIIC, is found at tRNA and 5S rRNA genes, and targets their repressor Maf1. Proc Natl Acad Sci USA 107:11823–11828

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Klein C, Struhl K (1994) Protein kinase A mediates growth-regulated expression of yeast ribosomal protein genes by modulating RAP1 transcriptional activity. Mol Cell Biol 14:1920–1928

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Kusnadi EP, Hannan KM, Hicks RJ, Hannan RD, Pearson RB, Kang J (2015) Regulation of rDNA transcription in response to growth factors, nutrients and energy. Gene 556:27–34

    Article  CAS  PubMed  Google Scholar 

  • Lee J, Moir RD, Willis IM (2009) Regulation of RNA polymerase III transcription involves SCH9-dependent and SCH9-independent branches of the target of rapamycin (TOR) pathway. J Biol Chem 8:12604–12608

    Article  CAS  Google Scholar 

  • Lee MV, Topper SE, Hubler SL, Hose J, Wenger CD, Coon JJ, Gasch AP (2011) A dynamic model of proteome changes reveals new roles for transcript alteration in yeast. Mol Syst Biol. 19:514

    Google Scholar 

  • Levav-Cohen Y, Goldberg Z, Tan KH, Alsheich-Bartok O, Zuckerman V, Haupt S, Haupt Y (2014) The p53-Mdm2 loop: a critical juncture of stress response. Subcell Biochem 85:161–186

    Article  PubMed  Google Scholar 

  • Leveille N, Melo CA, Rooijers K, Diaz-Lagares A, Melo SA, Korkmaz G, Lopes R, Akbari Moqadam F, Maia AR, Wijchers PJ, Geeven G, den Boer ML, Kalluri R, de Laat W, Esteller M, Agami R (2015) Genome-wide profiling of p53-regulated enhancer RNAs uncovers a subset of enhancers controlled by a lncRNA. Nat Commun 6:6520

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Levy SF, Ziv N, Siegal ML (2012) Bet hedging in yeast by heterogeneous, age-correlated expression of a stress protectant. PLoS Biol 10:e1001325

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Li H, Tsang CK, Watkins M, Bertram PG, Zheng XF (2006) Nutrient regulates Tor1 nuclear localization and association with rDNA promoter. Nature 442:1058–1061

    Article  CAS  PubMed  Google Scholar 

  • Lippman SI, Broach JR (2009) Protein kinase A and TORC1 activate genes for ribosomal biogenesis by inactivating repressors encoded by Dot6 and its homolog Tod6. Proc Natl Acad Sci USA 106:19928–19933

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Liu B, Qian SB (2014) Translational reprogramming in cellular stress response. Wiley Interdiscip Rev RNA 5:301–315

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Lopez-Maury L, Marguerat S, Bahler J (2008) Tuning gene expression to changing environments: from rapid responses to evolutionary adaptation. Nat Rev Genet 9:583–593

    Article  CAS  PubMed  Google Scholar 

  • Lu C, Brauer MJ, Botstein D (2009) Slow growth induces heat-shock resistance in normal and respiratory-deficient yeast. Mol Biol Cell 20:891–903

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Magnuson B, Ekim B, Fingar DC (2012) Regulation and function of ribosomal protein S6 kinase (S6 K) within mTOR signalling networks. Biochem J 441:1–21

    Article  CAS  PubMed  Google Scholar 

  • Mamane Y, Petroulakis E, Rong L, Yoshida K, Ler LW, Sonenberg N (2004) eIF4E–from translation to transformation. Oncogene 23:3172–3179

    Article  CAS  PubMed  Google Scholar 

  • Marion RM, Regev A, Segal E, Barash Y, Koller D, Friedman N, O’Shea EK (2004) Sfp1 is a stress- and nutrient-sensitive regulator of ribosomal protein gene expression. Proc Natl Acad Sci USA 101:14315–14322

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Martin DE, Soulard A, Hall MN (2004) TOR regulates ribosomal protein gene expression via PKA and the Forkhead transcription factor FHL1. Cell 119:969–979

    Article  CAS  PubMed  Google Scholar 

  • Matthew EM, Hart LS, Astrinidis A, Navaraj A, Dolloff NG, Dicker DT, Henske EP, El-Deiry WS (2009) The p53 target Plk2 interacts with TSC proteins impacting mTOR signaling, tumor growth and chemosensitivity under hypoxic conditions. Cell Cycle 8:4168–4175

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Mayer C, Grummt I (2006) Ribosome biogenesis and cell growth: mTOR coordinates transcription by all three classes of nuclear RNA polymerases. Oncogene 25:6384–6391

    Article  CAS  PubMed  Google Scholar 

  • Mayer C, Zhao J, Yuan X, Grummt I (2004) mTOR-dependent activation of the transcription factor TIF-IA links rRNA synthesis to nutrient availability. Genes Dev 18:423–434

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Mendoza MC, Er EE, Blenis J (2011) The Ras-ERK and PI3 K-mTOR pathways: cross-talk and compensation. Trends Biochem Sci 36:320–328

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Menendez D, Inga A, Resnick MA (2009) The expanding universe of p53 targets. Nat Rev Cancer 9:724–737

    Article  CAS  PubMed  Google Scholar 

  • Meyuhas O, Dreazen A (2009) Ribosomal protein S6 kinase from TOP mRNAs to cell size. Prog Mol Biol Transl Sci 90:109–153

    Article  CAS  PubMed  Google Scholar 

  • Mirza A, Wu Q, Wang L, McClanahan T, Bishop WR, Gheyas F, Ding W, Hutchins B, Hockenberry T, Kirschmeier P, Greene JR, Liu S (2003) Global transcriptional program of p53 target genes during the process of apoptosis and cell cycle progression. Oncogene 22:3645–3654

    Article  CAS  PubMed  Google Scholar 

  • Mitchell A, Romano GH, Groisman B, Yona A, Dekel E, Kupiec M, Dahan O, Pilpel Y (2009) Adaptive prediction of environmental changes by microorganisms. Nature 460:220–224

    Article  CAS  PubMed  Google Scholar 

  • Moir RD, Lee J, Haeusler RA, Desai N, Engelke DR, Willis IM (2006) Protein kinase A regulates RNA polymerase III transcription through the nuclear localization of Maf1. Proc Natl Acad Sci USA 103:15044–15049

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Murray JI, Whitfield ML, Trinklein ND, Myers RM, Brown PO, Botstein D (2004) Diverse and specific gene expression responses to stresses in cultured human cells. Mol Biol Cell 15:2361–2374

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Nadal-Ribelles M, Conde N, Flores O, González-Vallinas J, Eyras E, Orozco M, de Nadal E, Posas F (2012) Hog1 bypasses stress-mediated down-regulation of transcription by RNA polymerase II redistribution and chromatin remodeling. Genome Biol 13:R106

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Nagiec MJ, Dohlman HG (2012) Checkpoints in a yeast differentiation pathway coordinate signaling during hyperosmotic stress. PLoS Genet 8:e1002437

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Nayak RR, Bernal WE, Lee JW, Kearns MJ, Cheung VG (2014) Stress-induced changes in gene interactions in human cells. Nucleic Acids Res 42:1757–1771

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Neuman-Silberberg FS, Bhattacharya S, Broach JR (1995) Nutrient availability and the RAS/cyclic AMP pathway both induce expression of ribosomal protein genes in Saccharomyces cerevisiae but by different mechanisms. Mol Biol Cell 15:3187–3196

    Article  CAS  Google Scholar 

  • Nikulenkov F, Spinnler C, Li H, Tonelli C, Shi Y, Turunen M, Kivioja T, Ignatiev I, Kel A, Taipale J, Selivanova G (2012) Insights into p53 transcriptional function via genome-wide chromatin occupancy and gene expression analysis. Cell Death Differ 19:1992–2002

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • O’Rourke SM, Herskowitz I (2004) Unique and redundant roles for HOG MAPK pathway components as revealed by whole-genome expression analysis. Mol Biol Cell 15:532–542

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Philippi A, Steinbauer R, Reiter A, Fath S, Leger-Silvestre I, Milkereit P, Griesenbeck J, Tschochner H (2010) TOR-dependent reduction in the expression level of Rrn3p lowers the activity of the yeast RNA Pol I machinery, but does not account for the strong inhibition of rRNA production. Nucleic Acids Res 38:5315–5326

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Proft M, Struhl K (2004) MAP kinase-mediated stress relief that precedes and regulates the timing of transcriptional induction. Cell 118:351–361

    Article  CAS  PubMed  Google Scholar 

  • Ramachandran V, Herman PK (2011) Antagonistic interactions between the cAMP-dependent protein kinase and Tor signaling pathways modulate cell growth in Saccharomyces cerevisiae. Genetics 187:441–454

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Regenberg B, Grotkjaer T, Winther O, Fausbøll A, Akesson M, Bro C, Hansen LK, Brunak S, Nielsen J (2006) Growth-rate regulated genes have profound impact on interpretation of transcriptome profiling in Saccharomyces cerevisiae. Genome Biol 7:R107

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Roux PP, Blenis J (2004) ERK and p38 MAPK-activated protein kinases: a family of protein kinases with diverse biological functions. Microbiol Mol Biol Rev 68:320–344

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Roux PP, Topisirovic I (2012) Regulation of mRNA translation by signaling pathways. Cold Spring Harb Perspect Biol 4:a012252

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Rudra D, Warner JR (2004) What better measure than ribosome synthesis? Genes Dev 18:2431–2436

    Article  CAS  PubMed  Google Scholar 

  • Saito H, Posas F (2012) Response to hyperosmotic stress. Genetics 192:289–318

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Schadt EE, Lamb J, Yang X, Zhu J, Edwards S, Guhathakurta D, Sieberts SK, Monks S, Reitman M, Zhang C, Lum PY, Leonardson A, Thieringer R, Metzger JM, Yang L, Castle J, Zhu H, Kash SF, Drake TA, Sachs A, Lusis AJ (2005) An integrative genomics approach to infer causal associations between gene expression and disease. Nat Genet 37:710–717

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Schlereth K, Heyl C, Krampitz AM, Mernberger M, Finkernagel F, Scharfe M, Jarek M, Leich E, Rosenwald A, Stiewe T (2013) Characterization of the p53 cistrome–DNA binding cooperativity dissects p53’s tumor suppressor functions. PLoS Genet 9:e1003726

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Schmelzle T, Beck T, Martin DE, Hall MN (2004) Activation of the RAS/cyclic AMP pathway suppresses a TOR deficiency in yeast. Mol Biol Cell 24:338–351

    Article  CAS  Google Scholar 

  • Shaw RJ, Cantley LC (2006) Ras, PI(3)K and mTOR signalling controls tumour cell growth. Nature 441:424–430

    Article  CAS  PubMed  Google Scholar 

  • Smith A, Ward MP, Garrett S (1998) Yeast PKA represses Msn2p/Msn4p-dependent gene expression to regulate growth, stress response and glycogen accumulation. EMBO J 17:3556–3564

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Soulard A, Cremonesi A, Moes S, Schütz F, Jenö P, Hall MN (2010) The rapamycin-sensitive phosphoproteome reveals that TOR controls PKA toward some but not all substrates. Mol Biol Cell 21:3475–3486

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Spriggs KA, Bushell M, Willis AE (2010) Translational regulation of gene expression during conditions of cell stress. Mol Cell 40:228–237

    Article  CAS  PubMed  Google Scholar 

  • Taylor JL, Szmulewitz RZ, Lotan T, Hickson J, Griend DV, Yamada SD, Macleod K, Rinker-Schaeffer CW (2008) New paradigms for the function of JNKK1/MKK4 in controlling growth of disseminated cancer cells. Cancer Lett 272:12–22

    Article  CAS  PubMed  Google Scholar 

  • Teige M, Scheikl E, Reiser V, Ruis H, Ammerer G (2001) Rck2, a member of the calmodulin-protein kinase family, links protein synthesis to high osmolarity MAP kinase signaling in budding yeast. Proc Natl Acad Sci U S A 98:5625–5630

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Thomas G (2000) An encore for ribosome biogenesis in the control of cell proliferation. Nat Cell Biol 2:E71–E72

    Article  CAS  PubMed  Google Scholar 

  • Uesono Y, Toh-E A (2002) Transient inhibition of translation initiation by osmotic stress. J Biol Chem 277:13848–13855

    Article  CAS  PubMed  Google Scholar 

  • Vogel C, Silva GM, Marcotte EM (2011) Protein expression regulation under oxidative stress. Mol Cell Proteomics 10(M111):009217

    PubMed  Google Scholar 

  • von der Haar T (2008) A quantitative estimation of the global translational activity in logarithmically growing yeast cells. BMC Syst Biol 2:87

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Vousden KH, Lu X (2002) Live or let die: the cell’s response to p53. Nat Rev Cancer 2:594–604

    Article  CAS  PubMed  Google Scholar 

  • Wang Y, Pierce M, Schneper L, Güldal CG, Zhang X, Tavazoie S, Broach JR (2004) Ras and Gpa2 mediate one branch of a redundant glucose signaling pathway in yeast. PLoS Biol 2:E128

    Article  PubMed Central  PubMed  Google Scholar 

  • Warner JR (1999) The economics of ribosome biosynthesis in yeast. Trends Biochem Sci 24:437–440

    Article  CAS  PubMed  Google Scholar 

  • Wei CL, Wu Q, Vega VB, Chiu KP, Ng P, Zhang T, Shahab A, Yong HC, Fu Y, Weng Z, Liu J, Zhao XD, Chew JL, Lee YL, Kuznetsov VA, Sung WK, Miller LD, Lim B, Liu ET, Yu Q, Ng HH, Ruan Y (2006) A global map of p53 transcription-factor binding sites in the human genome. Cell 124:207–219

    Article  CAS  PubMed  Google Scholar 

  • Westfall PJ, Patterson JC, Chen RE, Thorner J (2008) Stress resistance and signal fidelity independent of nuclear MAPK function. Proc Natl Acad Sci USA 105:12212–12217

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Willis IM, Moir RD (2007) Integration of nutritional and stress signaling pathways by Maf1. Trends Biochem Sci 32:51–53

    Article  CAS  PubMed  Google Scholar 

  • Wu C, Yosef N, Thalhamer T, Zhu C, Xiao S, Kishi Y, Regev A, Kuchroo VK (2013) Induction of pathogenic TH17 cells by inducible salt-sensing kinase SGK1. Nature 496:513–517

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Xiao L, Grove A (2009) Coordination of ribosomal protein and ribosomal RNA gene expression in response to TOR signaling. Curr Genomics 10:198–205

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Yaakov G, Duch A, García-Rubio M, Clotet J, Jimenez J, Aguilera A, Posas F (2009) The stress-activated protein kinase Hog1 mediates S phase delay in response to osmostress. Mol Biol Cell 20:3572–3582

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Zakrzewska A, van Eikenhorst G, Burggraaff JE, Vis DJ, Hoefsloot H, Delneri D, Oliver SG, Brul S, Smits GJ (2011) Genome-wide analysis of yeast stress survival and tolerance acquisition to analyze the central trade-off between growth rate and cellular robustness. Mol Biol Cell 22:4435–4446

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Zarubin T, Han J (2005) Activation and signaling of the p38 MAP kinase pathway. Cell Res 15:11–18

    Article  CAS  PubMed  Google Scholar 

  • Zhai W, Comai L (2000) Repression of RNA polymerase I transcription by the tumor suppressor p53. Mol Cell Biol 20:5930–5938

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Zheng M, Wang YH, Wu XN, Wu SQ, Lu BJ, Dong MQ, Zhang H, Sun P, Lin SC, Guan KL, Han J (2011) Inactivation of Rheb by PRAK-mediated phosphorylation is essential for energy-depletion-induced suppression of mTORC1. Nat Cell Biol 13:263–272

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Zurita-Martinez SA, Cardenas ME (2005) Tor and cyclic AMP-protein kinase a: two parallel pathways regulating expression of genes required for cell growth. Eukaryot Cell 4:63–71

    Article  PubMed Central  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

We apologize to the authors of many important research studies that we were unable to cite due to space constraints. We thank M. MacGilvray for useful comments on the manuscript. This work was supported by NIH R01 GM083989 to A. P. G.

Author information

Authors and Affiliations

  1. Laboratory of Genetics, University of Wisconsin-Madison, Madison, WI, 53706, USA

    Yi-Hsuan Ho & Audrey P. Gasch

Authors
  1. Yi-Hsuan Ho
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Audrey P. Gasch
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Audrey P. Gasch.

Additional information

Communicated by M. Kupiec.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Ho, YH., Gasch, A.P. Exploiting the yeast stress-activated signaling network to inform on stress biology and disease signaling. Curr Genet 61, 503–511 (2015). https://doi.org/10.1007/s00294-015-0491-0

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00294-015-0491-0

Keywords

Search

Navigation