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. 1998 Jul 1;17(13):3556–3564. doi: 10.1093/emboj/17.13.3556

Yeast PKA represses Msn2p/Msn4p-dependent gene expression to regulate growth, stress response and glycogen accumulation.

A Smith 1, M P Ward 1, S Garrett 1
PMCID: PMC1170692  PMID: 9649426

Abstract

Yeast cAMP-dependent protein kinase (PKA) activity is essential for growth and antagonizes induction of the general stress response as well as accumulation of glycogen stores. Previous studies have suggested that the PKA effects on the two latter processes result in part from transcription repression. Here we show that transcription derepression that accompanies PKA depletion is dependent upon the presence of two redundant Zn2+-finger transcription factors, Msn2p and Msn4p. The Msn2p and Msn4p proteins were shown previously to act as positive transcriptional factors in the stress response pathway, and our results suggest that Msn2p and Msn4p also mediate PKA-dependent effects on stress response as well as glycogen accumulation genes. Interestingly, PKA activity is dispensable in a strain lacking Msn2p and Msn4p activity. Thus, Msn2p and Msn4p may antagonize PKAdependent growth by stimulating expression of genes that inhibit growth. In agreement with this model, Msn2p/Msn4p function is required for expression of a gene, YAK1, previously shown to antagonize PKA-dependent growth. These results suggest that Msn2p/Msn4p-dependent gene expression may account for all, or at least most, of the pleiotropic effects of yeast PKA, including growth regulation, response to stress and carbohydrate store accumulation.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Belazzi T., Wagner A., Wieser R., Schanz M., Adam G., Hartig A., Ruis H. Negative regulation of transcription of the Saccharomyces cerevisiae catalase T (CTT1) gene by cAMP is mediated by a positive control element. EMBO J. 1991 Mar;10(3):585–592. doi: 10.1002/j.1460-2075.1991.tb07985.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Broach J. R., Deschenes R. J. The function of ras genes in Saccharomyces cerevisiae. Adv Cancer Res. 1990;54:79–139. doi: 10.1016/s0065-230x(08)60809-x. [DOI] [PubMed] [Google Scholar]
  3. Cameron S., Levin L., Zoller M., Wigler M. cAMP-independent control of sporulation, glycogen metabolism, and heat shock resistance in S. cerevisiae. Cell. 1988 May 20;53(4):555–566. doi: 10.1016/0092-8674(88)90572-7. [DOI] [PubMed] [Google Scholar]
  4. Cannon J. F., Tatchell K. Characterization of Saccharomyces cerevisiae genes encoding subunits of cyclic AMP-dependent protein kinase. Mol Cell Biol. 1987 Aug;7(8):2653–2663. doi: 10.1128/mcb.7.8.2653. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Casadaban M. J., Martinez-Arias A., Shapira S. K., Chou J. Beta-galactosidase gene fusions for analyzing gene expression in escherichia coli and yeast. Methods Enzymol. 1983;100:293–308. doi: 10.1016/0076-6879(83)00063-4. [DOI] [PubMed] [Google Scholar]
  6. Christ C., Tye B. K. Functional domains of the yeast transcription/replication factor MCM1. Genes Dev. 1991 May;5(5):751–763. doi: 10.1101/gad.5.5.751. [DOI] [PubMed] [Google Scholar]
  7. Cuevo R. S., Garrett S., Horowitz J. M. Detection and functional characterization of p180, a novel cell cycle regulated yeast transcription factor that binds retinoblastoma control elements. J Biol Chem. 1997 Feb 7;272(6):3813–3822. doi: 10.1074/jbc.272.6.3813. [DOI] [PubMed] [Google Scholar]
  8. Engelberg D., Zandi E., Parker C. S., Karin M. The yeast and mammalian Ras pathways control transcription of heat shock genes independently of heat shock transcription factor. Mol Cell Biol. 1994 Jul;14(7):4929–4937. doi: 10.1128/mcb.14.7.4929. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Estruch F., Carlson M. Two homologous zinc finger genes identified by multicopy suppression in a SNF1 protein kinase mutant of Saccharomyces cerevisiae. Mol Cell Biol. 1993 Jul;13(7):3872–3881. doi: 10.1128/mcb.13.7.3872. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Finley R. L., Jr, Chen S., Ma J., Byrne P., West R. W., Jr Opposing regulatory functions of positive and negative elements in UASG control transcription of the yeast GAL genes. Mol Cell Biol. 1990 Nov;10(11):5663–5670. doi: 10.1128/mcb.10.11.5663. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. François J. M., Thompson-Jaeger S., Skroch J., Zellenka U., Spevak W., Tatchell K. GAC1 may encode a regulatory subunit for protein phosphatase type 1 in Saccharomyces cerevisiae. EMBO J. 1992 Jan;11(1):87–96. doi: 10.1002/j.1460-2075.1992.tb05031.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Garrett S., Broach J. 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. 1989 Sep;3(9):1336–1348. doi: 10.1101/gad.3.9.1336. [DOI] [PubMed] [Google Scholar]
  13. Garrett S., Menold M. M., Broach J. R. The Saccharomyces cerevisiae YAK1 gene encodes a protein kinase that is induced by arrest early in the cell cycle. Mol Cell Biol. 1991 Aug;11(8):4045–4052. doi: 10.1128/mcb.11.8.4045. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Gimeno C. J., Ljungdahl P. O., Styles C. A., Fink G. R. Unipolar cell divisions in the yeast S. cerevisiae lead to filamentous growth: regulation by starvation and RAS. Cell. 1992 Mar 20;68(6):1077–1090. doi: 10.1016/0092-8674(92)90079-r. [DOI] [PubMed] [Google Scholar]
  15. Görner W., Durchschlag E., Martinez-Pastor M. T., Estruch F., Ammerer G., Hamilton B., Ruis H., Schüller C. Nuclear localization of the C2H2 zinc finger protein Msn2p is regulated by stress and protein kinase A activity. Genes Dev. 1998 Feb 15;12(4):586–597. doi: 10.1101/gad.12.4.586. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Hardy T. A., Huang D., Roach P. J. Interactions between cAMP-dependent and SNF1 protein kinases in the control of glycogen accumulation in Saccharomyces cerevisiae. J Biol Chem. 1994 Nov 11;269(45):27907–27913. [PubMed] [Google Scholar]
  17. Hartley A. D., Ward M. P., Garrett S. The Yak1 protein kinase of Saccharomyces cerevisiae moderates thermotolerance and inhibits growth by an Sch9 protein kinase-independent mechanism. Genetics. 1994 Feb;136(2):465–474. doi: 10.1093/genetics/136.2.465. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Hubbard E. J., Yang X. L., Carlson M. Relationship of the cAMP-dependent protein kinase pathway to the SNF1 protein kinase and invertase expression in Saccharomyces cerevisiae. Genetics. 1992 Jan;130(1):71–80. doi: 10.1093/genetics/130.1.71. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Johnston G. C., Pringle J. R., Hartwell L. H. Coordination of growth with cell division in the yeast Saccharomyces cerevisiae. Exp Cell Res. 1977 Mar 1;105(1):79–98. doi: 10.1016/0014-4827(77)90154-9. [DOI] [PubMed] [Google Scholar]
  20. Klein C., Struhl K. Protein kinase A mediates growth-regulated expression of yeast ribosomal protein genes by modulating RAP1 transcriptional activity. Mol Cell Biol. 1994 Mar;14(3):1920–1928. doi: 10.1128/mcb.14.3.1920. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Mager W. H., De Kruijff A. J. Stress-induced transcriptional activation. Microbiol Rev. 1995 Sep;59(3):506–531. doi: 10.1128/mr.59.3.506-531.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Mai B., Breeden L. Xbp1, a stress-induced transcriptional repressor of the Saccharomyces cerevisiae Swi4/Mbp1 family. Mol Cell Biol. 1997 Nov;17(11):6491–6501. doi: 10.1128/mcb.17.11.6491. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Marchler G., Schüller C., Adam G., Ruis H. A Saccharomyces cerevisiae UAS element controlled by protein kinase A activates transcription in response to a variety of stress conditions. EMBO J. 1993 May;12(5):1997–2003. doi: 10.1002/j.1460-2075.1993.tb05849.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Markwardt D. D., Garrett J. M., Eberhardy S., Heideman W. Activation of the Ras/cyclic AMP pathway in the yeast Saccharomyces cerevisiae does not prevent G1 arrest in response to nitrogen starvation. J Bacteriol. 1995 Dec;177(23):6761–6765. doi: 10.1128/jb.177.23.6761-6765.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Martínez-Pastor M. T., Marchler G., Schüller C., Marchler-Bauer A., Ruis H., Estruch F. The Saccharomyces cerevisiae zinc finger proteins Msn2p and Msn4p are required for transcriptional induction through the stress response element (STRE). EMBO J. 1996 May 1;15(9):2227–2235. [PMC free article] [PubMed] [Google Scholar]
  26. Neuman-Silberberg F. S., Bhattacharya S., Broach J. R. Nutrient availability and the RAS/cyclic AMP pathway both induce expression of ribosomal protein genes in Saccharomyces cerevisiae but by different mechanisms. Mol Cell Biol. 1995 Jun;15(6):3187–3196. doi: 10.1128/mcb.15.6.3187. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Perkins D. D. Biochemical Mutants in the Smut Fungus Ustilago Maydis. Genetics. 1949 Sep;34(5):607–626. doi: 10.1093/genetics/34.5.607. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Ruis H., Schüller C. Stress signaling in yeast. Bioessays. 1995 Nov;17(11):959–965. doi: 10.1002/bies.950171109. [DOI] [PubMed] [Google Scholar]
  29. Russell P., Moreno S., Reed S. I. Conservation of mitotic controls in fission and budding yeasts. Cell. 1989 Apr 21;57(2):295–303. doi: 10.1016/0092-8674(89)90967-7. [DOI] [PubMed] [Google Scholar]
  30. Schmitt A. P., McEntee K. Msn2p, a zinc finger DNA-binding protein, is the transcriptional activator of the multistress response in Saccharomyces cerevisiae. Proc Natl Acad Sci U S A. 1996 Jun 11;93(12):5777–5782. doi: 10.1073/pnas.93.12.5777. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Schüller C., Brewster J. L., Alexander M. R., Gustin M. C., Ruis H. The HOG pathway controls osmotic regulation of transcription via the stress response element (STRE) of the Saccharomyces cerevisiae CTT1 gene. EMBO J. 1994 Sep 15;13(18):4382–4389. doi: 10.1002/j.1460-2075.1994.tb06758.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Sikorski R. S., Hieter P. A system of shuttle vectors and yeast host strains designed for efficient manipulation of DNA in Saccharomyces cerevisiae. Genetics. 1989 May;122(1):19–27. doi: 10.1093/genetics/122.1.19. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Thompson-Jaeger S., François J., Gaughran J. P., Tatchell K. Deletion of SNF1 affects the nutrient response of yeast and resembles mutations which activate the adenylate cyclase pathway. Genetics. 1991 Nov;129(3):697–706. doi: 10.1093/genetics/129.3.697. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Timblin B. K., Bergman L. W. Elevated expression of stress response genes resulting from deletion of the PHO85 gene. Mol Microbiol. 1997 Dec;26(5):981–990. doi: 10.1046/j.1365-2958.1997.6352004.x. [DOI] [PubMed] [Google Scholar]
  35. Varela J. C., Praekelt U. M., Meacock P. A., Planta R. J., Mager W. H. The Saccharomyces cerevisiae HSP12 gene is activated by the high-osmolarity glycerol pathway and negatively regulated by protein kinase A. Mol Cell Biol. 1995 Nov;15(11):6232–6245. doi: 10.1128/mcb.15.11.6232. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Ward M. P., Garrett S. Suppression of a yeast cyclic AMP-dependent protein kinase defect by overexpression of SOK1, a yeast gene exhibiting sequence similarity to a developmentally regulated mouse gene. Mol Cell Biol. 1994 Sep;14(9):5619–5627. doi: 10.1128/mcb.14.9.5619. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Ward M. P., Gimeno C. J., Fink G. R., Garrett S. SOK2 may regulate cyclic AMP-dependent protein kinase-stimulated growth and pseudohyphal development by repressing transcription. Mol Cell Biol. 1995 Dec;15(12):6854–6863. doi: 10.1128/mcb.15.12.6854. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Werner-Washburne M., Braun E., Johnston G. C., Singer R. A. Stationary phase in the yeast Saccharomyces cerevisiae. Microbiol Rev. 1993 Jun;57(2):383–401. doi: 10.1128/mr.57.2.383-401.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Woodcock D. M., Crowther P. J., Doherty J., Jefferson S., DeCruz E., Noyer-Weidner M., Smith S. S., Michael M. Z., Graham M. W. Quantitative evaluation of Escherichia coli host strains for tolerance to cytosine methylation in plasmid and phage recombinants. Nucleic Acids Res. 1989 May 11;17(9):3469–3478. doi: 10.1093/nar/17.9.3469. [DOI] [PMC free article] [PubMed] [Google Scholar]

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