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EMBO J. Sep 16, 1996; 15(18): 5001–5013.
PMCID: PMC452238

Coordinated regulation of gene expression by the cell cycle transcription factor Swi4 and the protein kinase C MAP kinase pathway for yeast cell integrity.

Abstract

Specific transcription in late G1, mediated by the transcription factors SBF (Swi4p-Swi6p) and MBF (Mbp1p-Swi6p), is crucial for cell cycle progression in budding yeast. In order to better understand the G1/S transition, we initiated a search for conditional mutations synthetic lethal with swi4delta. One of the isolated mutants, rsf8swi4delta, showed a growth defect due to cell lysis. rsf8 is allelic to PKC1, encoding a protein kinase C homologue which controls cell integrity. In the presence of the rsf8/(pkc1-8) mutation, a functional SBF but not MBF is required for viability. Importantly, swi4delta and swi6delta strains are hypersensitive to calcofluor white and SDS, indicating that they possess a weakened cell wall. Overexpression or ectopic expression of CLN did not suppress the pkc1-8swi4delta mutant phenotype, thus SBF must control cell integrity independently, rather than acting through CLN expression. We found that at least six genes involved in cell wall biosynthesis are periodically expressed at the G1/S phase boundary. In all six cases, cell cycle-regulated expression is due mainly to Swi4p. Finally, we found that the PKC1 MAP kinase pathway is a positive regulator of five of these cell wall genes, these genes being novel targets of regulation by this pathway. We suggest that SBF and the PKC1 MAP kinase pathway act in concert to maintain cell integrity during bud formation.

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Selected References

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  • Andrews BJ, Herskowitz I. The yeast SWI4 protein contains a motif present in developmental regulators and is part of a complex involved in cell-cycle-dependent transcription. Nature. 1989 Dec 14;342(6251):830–833. [PubMed]
  • Andrews BJ, Herskowitz I. Identification of a DNA binding factor involved in cell-cycle control of the yeast HO gene. Cell. 1989 Apr 7;57(1):21–29. [PubMed]
  • Benton BK, Tinkelenberg AH, Jean D, Plump SD, Cross FR. Genetic analysis of Cln/Cdc28 regulation of cell morphogenesis in budding yeast. EMBO J. 1993 Dec 15;12(13):5267–5275. [PMC free article] [PubMed]
  • Breeden L, Mikesell GE. Cell cycle-specific expression of the SWI4 transcription factor is required for the cell cycle regulation of HO transcription. Genes Dev. 1991 Jul;5(7):1183–1190. [PubMed]
  • Breeden L, Nasmyth K. Similarity between cell-cycle genes of budding yeast and fission yeast and the Notch gene of Drosophila. Nature. 1987 Oct 15;329(6140):651–654. [PubMed]
  • Breeden L, Nasmyth K. Cell cycle control of the yeast HO gene: cis- and trans-acting regulators. Cell. 1987 Feb 13;48(3):389–397. [PubMed]
  • Bulawa CE. Genetics and molecular biology of chitin synthesis in fungi. Annu Rev Microbiol. 1993;47:505–534. [PubMed]
  • Cid VJ, Durán A, del Rey F, Snyder MP, Nombela C, Sánchez M. Molecular basis of cell integrity and morphogenesis in Saccharomyces cerevisiae. Microbiol Rev. 1995 Sep;59(3):345–386. [PMC free article] [PubMed]
  • Corliss DA, White WE., Jr Fluorescence of yeast vitally stained with ethidium bromide and propidium iodide. J Histochem Cytochem. 1981 Jan;29(1):45–48. [PubMed]
  • Costigan C, Snyder M. SLK1, a yeast homolog of MAP kinase activators, has a RAS/cAMP-independent role in nutrient sensing. Mol Gen Genet. 1994 May 10;243(3):286–296. [PubMed]
  • Costigan C, Gehrung S, Snyder M. A synthetic lethal screen identifies SLK1, a novel protein kinase homolog implicated in yeast cell morphogenesis and cell growth. Mol Cell Biol. 1992 Mar;12(3):1162–1178. [PMC free article] [PubMed]
  • Cross FR. Cell cycle arrest caused by CLN gene deficiency in Saccharomyces cerevisiae resembles START-I arrest and is independent of the mating-pheromone signalling pathway. Mol Cell Biol. 1990 Dec;10(12):6482–6490. [PMC free article] [PubMed]
  • Cross FR. Starting the cell cycle: what's the point? Curr Opin Cell Biol. 1995 Dec;7(6):790–797. [PubMed]
  • Cross FR, Hoek M, McKinney JD, Tinkelenberg AH. Role of Swi4 in cell cycle regulation of CLN2 expression. Mol Cell Biol. 1994 Jul;14(7):4779–4787. [PMC free article] [PubMed]
  • Cvrcková F, Nasmyth K. Yeast G1 cyclins CLN1 and CLN2 and a GAP-like protein have a role in bud formation. EMBO J. 1993 Dec 15;12(13):5277–5286. [PMC free article] [PubMed]
  • Dekker LV, Parker PJ. Protein kinase C--a question of specificity. Trends Biochem Sci. 1994 Feb;19(2):73–77. [PubMed]
  • Di Como CJ, Chang H, Arndt KT. Activation of CLN1 and CLN2 G1 cyclin gene expression by BCK2. Mol Cell Biol. 1995 Apr;15(4):1835–1846. [PMC free article] [PubMed]
  • Dirick L, Böhm T, Nasmyth K. Roles and regulation of Cln-Cdc28 kinases at the start of the cell cycle of Saccharomyces cerevisiae. EMBO J. 1995 Oct 2;14(19):4803–4813. [PMC free article] [PubMed]
  • Douglas CM, Foor F, Marrinan JA, Morin N, Nielsen JB, Dahl AM, Mazur P, Baginsky W, Li W, el-Sherbeini M, et al. The Saccharomyces cerevisiae FKS1 (ETG1) gene encodes an integral membrane protein which is a subunit of 1,3-beta-D-glucan synthase. Proc Natl Acad Sci U S A. 1994 Dec 20;91(26):12907–12911. [PMC free article] [PubMed]
  • Epstein CB, Cross FR. CLB5: a novel B cyclin from budding yeast with a role in S phase. Genes Dev. 1992 Sep;6(9):1695–1706. [PubMed]
  • Herskowitz I. MAP kinase pathways in yeast: for mating and more. Cell. 1995 Jan 27;80(2):187–197. [PubMed]
  • Huang KN, Symington LS. Mutation of the gene encoding protein kinase C 1 stimulates mitotic recombination in Saccharomyces cerevisiae. Mol Cell Biol. 1994 Sep;14(9):6039–6045. [PMC free article] [PubMed]
  • Huang KN, Symington LS. Suppressors of a Saccharomyces cerevisiae pkc1 mutation identify alleles of the phosphatase gene PTC1 and of a novel gene encoding a putative basic leucine zipper protein. Genetics. 1995 Dec;141(4):1275–1285. [PMC free article] [PubMed]
  • Irie K, Takase M, Lee KS, Levin DE, Araki H, Matsumoto K, Oshima Y. MKK1 and MKK2, which encode Saccharomyces cerevisiae mitogen-activated protein kinase-kinase homologs, function in the pathway mediated by protein kinase C. Mol Cell Biol. 1993 May;13(5):3076–3083. [PMC free article] [PubMed]
  • Johnston LH, Lowndes NF. Cell cycle control of DNA synthesis in budding yeast. Nucleic Acids Res. 1992 May 25;20(10):2403–2410. [PMC free article] [PubMed]
  • Kamada Y, Jung US, Piotrowski J, Levin DE. The protein kinase C-activated MAP kinase pathway of Saccharomyces cerevisiae mediates a novel aspect of the heat shock response. Genes Dev. 1995 Jul 1;9(13):1559–1571. [PubMed]
  • Kanik-Ennulat C, Montalvo E, Neff N. Sodium orthovanadate-resistant mutants of Saccharomyces cerevisiae show defects in Golgi-mediated protein glycosylation, sporulation and detergent resistance. Genetics. 1995 Jul;140(3):933–943. [PMC free article] [PubMed]
  • Kilmartin JV, Dyos SL, Kershaw D, Finch JT. A spacer protein in the Saccharomyces cerevisiae spindle poly body whose transcript is cell cycle-regulated. J Cell Biol. 1993 Dec;123(5):1175–1184. [PMC free article] [PubMed]
  • Klis FM. Review: cell wall assembly in yeast. Yeast. 1994 Jul;10(7):851–869. [PubMed]
  • Koch C, Nasmyth K. Cell cycle regulated transcription in yeast. Curr Opin Cell Biol. 1994 Jun;6(3):451–459. [PubMed]
  • Koch C, Moll T, Neuberg M, Ahorn H, Nasmyth K. A role for the transcription factors Mbp1 and Swi4 in progression from G1 to S phase. Science. 1993 Sep 17;261(5128):1551–1557. [PubMed]
  • Lee KS, Levin DE. Dominant mutations in a gene encoding a putative protein kinase (BCK1) bypass the requirement for a Saccharomyces cerevisiae protein kinase C homolog. Mol Cell Biol. 1992 Jan;12(1):172–182. [PMC free article] [PubMed]
  • Lee KS, Irie K, Gotoh Y, Watanabe Y, Araki H, Nishida E, Matsumoto K, Levin DE. A yeast mitogen-activated protein kinase homolog (Mpk1p) mediates signalling by protein kinase C. Mol Cell Biol. 1993 May;13(5):3067–3075. [PMC free article] [PubMed]
  • Levin DE, Bartlett-Heubusch E. Mutants in the S. cerevisiae PKC1 gene display a cell cycle-specific osmotic stability defect. J Cell Biol. 1992 Mar;116(5):1221–1229. [PMC free article] [PubMed]
  • Levin DE, Errede B. The proliferation of MAP kinase signaling pathways in yeast. Curr Opin Cell Biol. 1995 Apr;7(2):197–202. [PubMed]
  • Levin DE, Fields FO, Kunisawa R, Bishop JM, Thorner J. A candidate protein kinase C gene, PKC1, is required for the S. cerevisiae cell cycle. Cell. 1990 Jul 27;62(2):213–224. [PubMed]
  • Levin DE, Bowers B, Chen CY, Kamada Y, Watanabe M. Dissecting the protein kinase C/MAP kinase signalling pathway of Saccharomyces cerevisiae. Cell Mol Biol Res. 1994;40(3):229–239. [PubMed]
  • Lew DJ, Reed SI. Morphogenesis in the yeast cell cycle: regulation by Cdc28 and cyclins. J Cell Biol. 1993 Mar;120(6):1305–1320. [PMC free article] [PubMed]
  • Lowndes NF, Johnson AL, Johnston LH. Coordination of expression of DNA synthesis genes in budding yeast by a cell-cycle regulated trans factor. Nature. 1991 Mar 21;350(6315):247–250. [PubMed]
  • Lowndes NF, Johnson AL, Breeden L, Johnston LH. SWI6 protein is required for transcription of the periodically expressed DNA synthesis genes in budding yeast. Nature. 1992 Jun 11;357(6378):505–508. [PubMed]
  • Mazzoni C, Zarov P, Rambourg A, Mann C. The SLT2 (MPK1) MAP kinase homolog is involved in polarized cell growth in Saccharomyces cerevisiae. J Cell Biol. 1993 Dec;123(6 Pt 2):1821–1833. [PMC free article] [PubMed]
  • Nasmyth K, Dirick L. The role of SWI4 and SWI6 in the activity of G1 cyclins in yeast. Cell. 1991 Sep 6;66(5):995–1013. [PubMed]
  • Nuoffer C, Jenö P, Conzelmann A, Riezman H. Determinants for glycophospholipid anchoring of the Saccharomyces cerevisiae GAS1 protein to the plasma membrane. Mol Cell Biol. 1991 Jan;11(1):27–37. [PMC free article] [PubMed]
  • Ogas J, Andrews BJ, Herskowitz I. Transcriptional activation of CLN1, CLN2, and a putative new G1 cyclin (HCS26) by SWI4, a positive regulator of G1-specific transcription. Cell. 1991 Sep 6;66(5):1015–1026. [PubMed]
  • Pammer M, Briza P, Ellinger A, Schuster T, Stucka R, Feldmann H, Breitenbach M. DIT101 (CSD2, CAL1), a cell cycle-regulated yeast gene required for synthesis of chitin in cell walls and chitosan in spore walls. Yeast. 1992 Dec;8(12):1089–1099. [PubMed]
  • Paravicini G, Cooper M, Friedli L, Smith DJ, Carpentier JL, Klig LS, Payton MA. The osmotic integrity of the yeast cell requires a functional PKC1 gene product. Mol Cell Biol. 1992 Nov;12(11):4896–4905. [PMC free article] [PubMed]
  • Ram AF, Wolters A, Ten Hoopen R, Klis FM. A new approach for isolating cell wall mutants in Saccharomyces cerevisiae by screening for hypersensitivity to calcofluor white. Yeast. 1994 Aug;10(8):1019–1030. [PubMed]
  • Ram AF, Brekelmans SS, Oehlen LJ, Klis FM. Identification of two cell cycle regulated genes affecting the beta 1,3-glucan content of cell walls in Saccharomyces cerevisiae. FEBS Lett. 1995 Jan 23;358(2):165–170. [PubMed]
  • Richardson HE, Wittenberg C, Cross F, Reed SI. An essential G1 function for cyclin-like proteins in yeast. Cell. 1989 Dec 22;59(6):1127–1133. [PubMed]
  • Roemer T, Paravicini G, Payton MA, Bussey H. Characterization of the yeast (1-->6)-beta-glucan biosynthetic components, Kre6p and Skn1p, and genetic interactions between the PKC1 pathway and extracellular matrix assembly. J Cell Biol. 1994 Oct;127(2):567–579. [PMC free article] [PubMed]
  • Schultz J, Ferguson B, Sprague GF., Jr Signal transduction and growth control in yeast. Curr Opin Genet Dev. 1995 Feb;5(1):31–37. [PubMed]
  • Shimizu J, Yoda K, Yamasaki M. The hypo-osmolarity-sensitive phenotype of the Saccharomyces cerevisiae hpo2 mutant is due to a mutation in PKC1, which regulates expression of beta-glucanase. Mol Gen Genet. 1994 Mar;242(6):641–648. [PubMed]
  • Storms RK, Ord RW, Greenwood MT, Mirdamadi B, Chu FK, Belfort M. Cell cycle-dependent expression of thymidylate synthase in Saccharomyces cerevisiae. Mol Cell Biol. 1984 Dec;4(12):2858–2864. [PMC free article] [PubMed]
  • Stuart D, Wittenberg C. Cell cycle-dependent transcription of CLN2 is conferred by multiple distinct cis-acting regulatory elements. Mol Cell Biol. 1994 Jul;14(7):4788–4801. [PMC free article] [PubMed]
  • Stuart D, Wittenberg C. CLN3, not positive feedback, determines the timing of CLN2 transcription in cycling cells. Genes Dev. 1995 Nov 15;9(22):2780–2794. [PubMed]
  • Thevelein JM. Signal transduction in yeast. Yeast. 1994 Dec;10(13):1753–1790. [PubMed]
  • Toone WM, Johnson AL, Banks GR, Toyn JH, Stuart D, Wittenberg C, Johnston LH. Rme1, a negative regulator of meiosis, is also a positive activator of G1 cyclin gene expression. EMBO J. 1995 Dec 1;14(23):5824–5832. [PMC free article] [PubMed]
  • Torres L, Martín H, García-Saez MI, Arroyo J, Molina M, Sánchez M, Nombela C. A protein kinase gene complements the lytic phenotype of Saccharomyces cerevisiae lyt2 mutants. Mol Microbiol. 1991 Nov;5(11):2845–2854. [PubMed]
  • Tyers M, Tokiwa G, Futcher B. Comparison of the Saccharomyces cerevisiae G1 cyclins: Cln3 may be an upstream activator of Cln1, Cln2 and other cyclins. EMBO J. 1993 May;12(5):1955–1968. [PMC free article] [PubMed]
  • Watanabe Y, Irie K, Matsumoto K. Yeast RLM1 encodes a serum response factor-like protein that may function downstream of the Mpk1 (Slt2) mitogen-activated protein kinase pathway. Mol Cell Biol. 1995 Oct;15(10):5740–5749. [PMC free article] [PubMed]
  • White JH, Barker DG, Nurse P, Johnston LH. Periodic transcription as a means of regulating gene expression during the cell cycle: contrasting modes of expression of DNA ligase genes in budding and fission yeast. EMBO J. 1986 Jul;5(7):1705–1709. [PMC free article] [PubMed]
  • Yip CL, Welch SK, Klebl F, Gilbert T, Seidel P, Grant FJ, O'Hara PJ, MacKay VL. Cloning and analysis of the Saccharomyces cerevisiae MNN9 and MNN1 genes required for complex glycosylation of secreted proteins. Proc Natl Acad Sci U S A. 1994 Mar 29;91(7):2723–2727. [PMC free article] [PubMed]
  • Zarzov P, Mazzoni C, Mann C. The SLT2(MPK1) MAP kinase is activated during periods of polarized cell growth in yeast. EMBO J. 1996 Jan 2;15(1):83–91. [PMC free article] [PubMed]

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