Msn2p and Msn4p Control a Large Number of Genes Induced at the Diauxic Transition Which Are Repressed by Cyclic AMP inSaccharomyces cerevisiae

ABSTRACT The multicopy suppressors of the snf1 defect, Msn2p and Msn4p transcription factors (Msn2/4p), activate genes through the stress-responsive cis element (CCCCT) in response to various stresses. This cis element is also the target for repression by the cyclic AMP (cAMP)-signaling pathway. We analyzed the two-dimensional gel electrophoresis pattern of protein synthesis of themsn2 msn4 double mutant and compared it with that of the wild-type strain during exponential growth phase and at the diauxic transition. Thirty-nine gene products (including those ofALD3, GDH3, GLK1, GPP2,HSP104, HXK1, PGM2,SOD2, SSA3, SSA4, TKL2,TPS1, and YBR149W) are dependent upon Msn2/4p for their induction at the diauxic transition. The expression of all these genes is repressed by cAMP. Thirty other genes identified during this study are still inducible in the mutant. A subset of these genes were found to be superinduced at the diauxic transition, and others were subject to cAMP repression (including ACH1,ADH2, ALD6, ATP2, GPD1,ICL1, and KGD2). We conclude from this analysis that Msn2/4p control a large number of genes induced at the diauxic transition but that other, as-yet-uncharacterized regulators, also contribute to this response. In addition, we show here that cAMP repression applies to both Msn2/4p-dependent and -independent control of gene expression at the diauxic shift. Furthermore, the fact that all the Msn2/4p gene targets are subject to cAMP repression suggests that these regulators could be targets for the cAMP-signaling pathway.

[1]  M. M. Bradford.  A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. , 1976, Analytical biochemistry.

[2]  M. Wigler,et al.  Genetic analysis of yeast RAS1 and RAS2 genes , 1984, Cell.

[3]  M. Wigler,et al.  In yeast, RAS proteins are controlling elements of adenylate cyclase , 1985, Cell.

[4]  H. Boucherie,et al.  Protein synthesis during transition and stationary phases under glucose limitation in Saccharomyces cerevisiae , 1985, Journal of bacteriology.

[5]  Kunihiro Matsumoto,et al.  Genetic analysis of the role of cAMP in yeast , 1985, Yeast.

[6]  M. Carlson,et al.  Upstream region of the SUC2 gene confers regulated expression to a heterologous gene in Saccharomyces cerevisiae , 1985, Molecular and cellular biology.

[7]  L. C. Robinson,et al.  RAS2 of Saccharomyces cerevisiae is required for gluconeogenic growth and proper response to nutrient limitation. , 1985, Proceedings of the National Academy of Sciences of the United States of America.

[8]  T. Boller,et al.  Rapid changes of heat and desiccation tolerance correlated with changes of trehalose content in Saccharomyces cerevisiae cells subjected to temperature shifts , 1987, FEBS letters.

[9]  J. François,et al.  Changes in the concentration of cAMP, fructose 2,6-bisphosphate and related metabolites and enzymes in Saccharomyces cerevisiae during growth on glucose. , 1987, European journal of biochemistry.

[10]  Gerald R. Fink,et al.  Methods in Yeast Genetics: A Laboratory Course Manual , 1987 .

[11]  M. Jacquet,et al.  Cyclic AMP controls the switch between division cycle and resting state programs in response to ammonium availability in Saccharomyces cerevisiae , 1987, Yeast.

[12]  J. Thevelein,et al.  Requirement of one functional RAS gene and inability of an oncogenic ras variant to mediate the glucose-induced cyclic AMP signal in the yeast Saccharomyces cerevisiae , 1988, Molecular and cellular biology.

[13]  K. Matsumoto,et al.  Dual regulation of the expression of the polyubiquitin gene by cyclic AMP and heat shock in yeast. , 1988, The EMBO journal.

[14]  M. Werner-Washburne,et al.  Yeast Hsp70 RNA levels vary in response to the physiological status of the cell , 1989, Journal of bacteriology.

[15]  C. Denis,et al.  Cyclic AMP-dependent protein kinase phosphorylates and inactivates the yeast transcriptional activator ADR1 , 1989, Cell.

[16]  E. Craig,et al.  Regulation of a yeast HSP70 gene by a cAMP responsive transcriptional control element. , 1990, The EMBO journal.

[17]  Multiple forms of transketolase. , 1990, Biochemistry international.

[18]  K. McEntee,et al.  Evidence for a heat shock transcription factor-independent mechanism for heat shock induction of transcription in Saccharomyces cerevisiae. , 1990, Proceedings of the National Academy of Sciences of the United States of America.

[19]  H. Boucherie,et al.  Induction of a heat‐shock‐type response in Saccharomyces cerevisiae following glucose limitation , 1991, Yeast.

[20]  J. François,et al.  Deletion of SNF1 affects the nutrient response of yeast and resembles mutations which activate the adenylate cyclase pathway. , 1991, Genetics.

[21]  C. Verrips,et al.  Analysis of transcription and translation of glycolytic enzymes in glucose-limited continuous cultures of Saccharomyces cerevisiae. , 1992, Journal of general microbiology.

[22]  Gerald R. Fink,et al.  Unipolar cell divisions in the yeast S. cerevisiae lead to filamentous growth: Regulation by starvation and RAS , 1992, Cell.

[23]  W. Heideman,et al.  Changes in gene expression in the Ras/adenylate cyclase system of Saccharomyces cerevisiae: correlation with cAMP levels and growth arrest. , 1993, Molecular biology of the cell.

[24]  M. Carlson,et al.  Two homologous zinc finger genes identified by multicopy suppression in a SNF1 protein kinase mutant of Saccharomyces cerevisiae , 1993, Molecular and cellular biology.

[25]  G. Adam,et al.  A Saccharomyces cerevisiae UAS element controlled by protein kinase A activates transcription in response to a variety of stress conditions. , 1993, The EMBO journal.

[26]  The yeast and mammalian Ras pathways control transcription of heat shock genes independently of heat shock transcription factor. , 1994, Molecular and cellular biology.

[27]  M. Werner-Washburne,et al.  Protein synthesis in long-term stationary-phase cultures of Saccharomyces cerevisiae , 1994, Journal of bacteriology.

[28]  G. Thireos,et al.  Yap1p, a yeast transcriptional activator that mediates multidrug resistance, regulates the metabolic stress response. , 1994, The EMBO journal.

[29]  R. Serrano,et al.  A genomic locus in Saccharomyces cerevisiae with four genes up‐regulated by osmotic stress , 1995, Molecular microbiology.

[30]  P. Slonimski,et al.  Two‐Dimensional protein map of Saccharomyces cerevisiae: Construction of a gene–protein index , 1995, Yeast.

[31]  W. H. Mager,et al.  Stress-induced transcriptional activation. , 1995, Microbiological reviews.

[32]  D. Laporte,et al.  Response of a yeast glycogen synthase gene to stress , 1995, Molecular microbiology.

[33]  W. H. Mager,et al.  The Saccharomyces cerevisiae HSP12 gene is activated by the high-osmolarity glycerol pathway and negatively regulated by protein kinase A , 1995, Molecular and cellular biology.

[34]  I. Pelletier,et al.  A bacterial esterase is homologous with non-haem haloperoxidases and displays brominating activity. , 1995, Microbiology.

[35]  M. Jacquet,et al.  High cAMP levels antagonize the reprogramming of gene expression that occurs at the diauxic shift in Saccharomyces cerevisiae. , 1996, Microbiology.

[36]  M. Perrot,et al.  Two‐dimensional gel protein database of Saccharomyces cerevisiae , 1996, Electrophoresis.

[37]  A. Schmitt,et al.  Msn2p, a zinc finger DNA-binding protein, is the transcriptional activator of the multistress response in Saccharomyces cerevisiae. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[38]  A. Marchler-Bauer,et al.  The Saccharomyces cerevisiae zinc finger proteins Msn2p and Msn4p are required for transcriptional induction through the stress response element (STRE). , 1996, The EMBO journal.

[39]  A. Blomberg,et al.  Identification of two‐dimensional gel electrophoresis resolved yeast proteins by matrix‐assisted laser desorption ionization mass spectrometry , 1997, Electrophoresis.

[40]  Wei Zhou,et al.  Characterization of the Yeast Transcriptome , 1997, Cell.

[41]  C. Grant,et al.  Stationary‐phase regulation of the Saccharomyces cerevisiaeSOD2 gene is dependent on additive effects of HAP2/3/4/5‐ and STRE‐binding elements , 1997, Molecular microbiology.

[42]  P. Brown,et al.  Exploring the metabolic and genetic control of gene expression on a genomic scale. , 1997, Science.

[43]  A. Blomberg,et al.  Metabolic and Regulatory Changes Associated with Growth of Saccharomyces cerevisiae in 1.4 M NaCl , 1997, The Journal of Biological Chemistry.

[44]  J. François,et al.  Effects of various types of stress on the metabolism of reserve carbohydrates in Saccharomyces cerevisiae: genetic evidence for a stress-induced recycling of glycogen and trehalose. , 1997, Microbiology.

[45]  K. M. Dombek,et al.  Cyclic AMP-dependent protein kinase inhibits ADH2 expression in part by decreasing expression of the transcription factor gene ADR1 , 1997, Molecular and cellular biology.