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. 1996 Jun;16(6):2830–2837. doi: 10.1128/mcb.16.6.2830

Ste12 and Mcm1 regulate cell cycle-dependent transcription of FAR1.

L J Oehlen 1, J D McKinney 1, F R Cross 1
PMCID: PMC231275  PMID: 8649392

Abstract

The transcripts of many genes involved in Saccharomyces cerevisiae mating were found to fluctuate during the cell cycle. In the absence of a functional Ste12 transcription factor, both the levels and the cell cycle pattern of expression of these genes were affected. FUS1 and AGA1 levels, which are maximally expressed only in G1-phase cells, were strongly reduced in ste12- cells. The cell cycle transcription pattern for FAR1 was changed in ste12- cells: the gene was still significantly expressed in G2/M, but transcript levels were strongly reduced in G1 phase, resulting in a lack of Far1 protein accumulation. G2/M transcription of FAR1 was dependent on the transcription factor Mcm1, and expression of a gene with Mcm1 fused to a strong transcriptional activation domain resulted in increased levels of FAR1 transcription. The pattern of cell cycle-regulated transcription of FAR1 could involve combinatorial control of Ste12 and Mcm1. Forced G1 expression of FAR1 from the GAL1 promoter resorted the ability to arrest in response to pheromone in ste12-cells. This indicates that transcription of FAR1 in the G1 phase is essential for accumulation of the protein and for pheromone-induced cell cycle arrest.

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Selected References

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

  1. Althoefer H., Schleiffer A., Wassmann K., Nordheim A., Ammerer G. Mcm1 is required to coordinate G2-specific transcription in Saccharomyces cerevisiae. Mol Cell Biol. 1995 Nov;15(11):5917–5928. doi: 10.1128/mcb.15.11.5917. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Ammerer G. Identification, purification, and cloning of a polypeptide (PRTF/GRM) that binds to mating-specific promoter elements in yeast. Genes Dev. 1990 Feb;4(2):299–312. doi: 10.1101/gad.4.2.299. [DOI] [PubMed] [Google Scholar]
  3. Amon A., Tyers M., Futcher B., Nasmyth K. Mechanisms that help the yeast cell cycle clock tick: G2 cyclins transcriptionally activate G2 cyclins and repress G1 cyclins. Cell. 1993 Sep 24;74(6):993–1007. doi: 10.1016/0092-8674(93)90722-3. [DOI] [PubMed] [Google Scholar]
  4. Bardwell L., Cook J. G., Inouye C. J., Thorner J. Signal propagation and regulation in the mating pheromone response pathway of the yeast Saccharomyces cerevisiae. Dev Biol. 1994 Dec;166(2):363–379. doi: 10.1006/dbio.1994.1323. [DOI] [PubMed] [Google Scholar]
  5. Bender A., Sprague G. F., Jr MAT alpha 1 protein, a yeast transcription activator, binds synergistically with a second protein to a set of cell-type-specific genes. Cell. 1987 Aug 28;50(5):681–691. doi: 10.1016/0092-8674(87)90326-6. [DOI] [PubMed] [Google Scholar]
  6. Bruhn L., Sprague G. F., Jr MCM1 point mutants deficient in expression of alpha-specific genes: residues important for interaction with alpha 1. Mol Cell Biol. 1994 Apr;14(4):2534–2544. doi: 10.1128/mcb.14.4.2534. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Chang F., Herskowitz I. Identification of a gene necessary for cell cycle arrest by a negative growth factor of yeast: FAR1 is an inhibitor of a G1 cyclin, CLN2. Cell. 1990 Nov 30;63(5):999–1011. doi: 10.1016/0092-8674(90)90503-7. [DOI] [PubMed] [Google Scholar]
  8. Cross F. R., Tinkelenberg A. H. A potential positive feedback loop controlling CLN1 and CLN2 gene expression at the start of the yeast cell cycle. Cell. 1991 May 31;65(5):875–883. doi: 10.1016/0092-8674(91)90394-e. [DOI] [PubMed] [Google Scholar]
  9. Dietzel C., Kurjan J. Pheromonal regulation and sequence of the Saccharomyces cerevisiae SST2 gene: a model for desensitization to pheromone. Mol Cell Biol. 1987 Dec;7(12):4169–4177. doi: 10.1128/mcb.7.12.4169. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Dolan J. W., Fields S. Overproduction of the yeast STE12 protein leads to constitutive transcriptional induction. Genes Dev. 1990 Apr;4(4):492–502. doi: 10.1101/gad.4.4.492. [DOI] [PubMed] [Google Scholar]
  11. Dolan J. W., Kirkman C., Fields S. The yeast STE12 protein binds to the DNA sequence mediating pheromone induction. Proc Natl Acad Sci U S A. 1989 Aug;86(15):5703–5707. doi: 10.1073/pnas.86.15.5703. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Elion E. A., Grisafi P. L., Fink G. R. FUS3 encodes a cdc2+/CDC28-related kinase required for the transition from mitosis into conjugation. Cell. 1990 Feb 23;60(4):649–664. doi: 10.1016/0092-8674(90)90668-5. [DOI] [PubMed] [Google Scholar]
  13. Elion E. A., Satterberg B., Kranz J. E. FUS3 phosphorylates multiple components of the mating signal transduction cascade: evidence for STE12 and FAR1. Mol Biol Cell. 1993 May;4(5):495–510. doi: 10.1091/mbc.4.5.495. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Errede B., Ammerer G. STE12, a protein involved in cell-type-specific transcription and signal transduction in yeast, is part of protein-DNA complexes. Genes Dev. 1989 Sep;3(9):1349–1361. doi: 10.1101/gad.3.9.1349. [DOI] [PubMed] [Google Scholar]
  15. Fields S., Chaleff D. T., Sprague G. F., Jr Yeast STE7, STE11, and STE12 genes are required for expression of cell-type-specific genes. Mol Cell Biol. 1988 Feb;8(2):551–556. doi: 10.1128/mcb.8.2.551. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Fields S., Herskowitz I. Regulation by the yeast mating-type locus of STE12, a gene required for cell-type-specific expression. Mol Cell Biol. 1987 Oct;7(10):3818–3821. doi: 10.1128/mcb.7.10.3818. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Gartner A., Nasmyth K., Ammerer G. Signal transduction in Saccharomyces cerevisiae requires tyrosine and threonine phosphorylation of FUS3 and KSS1. Genes Dev. 1992 Jul;6(7):1280–1292. doi: 10.1101/gad.6.7.1280. [DOI] [PubMed] [Google Scholar]
  18. Ghiara J. B., Richardson H. E., Sugimoto K., Henze M., Lew D. J., Wittenberg C., Reed S. I. A cyclin B homolog in S. cerevisiae: chronic activation of the Cdc28 protein kinase by cyclin prevents exit from mitosis. Cell. 1991 Apr 5;65(1):163–174. doi: 10.1016/0092-8674(91)90417-w. [DOI] [PubMed] [Google Scholar]
  19. Hartig A., Holly J., Saari G., MacKay V. L. Multiple regulation of STE2, a mating-type-specific gene of Saccharomyces cerevisiae. Mol Cell Biol. 1986 Jun;6(6):2106–2114. doi: 10.1128/mcb.6.6.2106. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Hartwell L. H. Mutants of Saccharomyces cerevisiae unresponsive to cell division control by polypeptide mating hormone. J Cell Biol. 1980 Jun;85(3):811–822. doi: 10.1083/jcb.85.3.811. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Hwang-Shum J. J., Hagen D. C., Jarvis E. E., Westby C. A., Sprague G. F., Jr Relative contributions of MCM1 and STE12 to transcriptional activation of a- and alpha-specific genes from Saccharomyces cerevisiae. Mol Gen Genet. 1991 Jun;227(2):197–204. doi: 10.1007/BF00259671. [DOI] [PubMed] [Google Scholar]
  22. Kirkman-Correia C., Stroke I. L., Fields S. Functional domains of the yeast STE12 protein, a pheromone-responsive transcriptional activator. Mol Cell Biol. 1993 Jun;13(6):3765–3772. doi: 10.1128/mcb.13.6.3765. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Koch C., Nasmyth K. Cell cycle regulated transcription in yeast. Curr Opin Cell Biol. 1994 Jun;6(3):451–459. doi: 10.1016/0955-0674(94)90039-6. [DOI] [PubMed] [Google Scholar]
  24. Kronstad J. W., Holly J. A., MacKay V. L. A yeast operator overlaps an upstream activation site. Cell. 1987 Jul 31;50(3):369–377. doi: 10.1016/0092-8674(87)90491-0. [DOI] [PubMed] [Google Scholar]
  25. Kuo M. H., Grayhack E. A library of yeast genomic MCM1 binding sites contains genes involved in cell cycle control, cell wall and membrane structure, and metabolism. Mol Cell Biol. 1994 Jan;14(1):348–359. doi: 10.1128/mcb.14.1.348. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Lydall D., Ammerer G., Nasmyth K. A new role for MCM1 in yeast: cell cycle regulation of SW15 transcription. Genes Dev. 1991 Dec;5(12B):2405–2419. doi: 10.1101/gad.5.12b.2405. [DOI] [PubMed] [Google Scholar]
  27. Maher M., Cong F., Kindelberger D., Nasmyth K., Dalton S. Cell cycle-regulated transcription of the CLB2 gene is dependent on Mcm1 and a ternary complex factor. Mol Cell Biol. 1995 Jun;15(6):3129–3137. doi: 10.1128/mcb.15.6.3129. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. McCaffrey G., Clay F. J., Kelsay K., Sprague G. F., Jr Identification and regulation of a gene required for cell fusion during mating of the yeast Saccharomyces cerevisiae. Mol Cell Biol. 1987 Aug;7(8):2680–2690. doi: 10.1128/mcb.7.8.2680. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. McKinney J. D., Chang F., Heintz N., Cross F. R. Negative regulation of FAR1 at the Start of the yeast cell cycle. Genes Dev. 1993 May;7(5):833–843. doi: 10.1101/gad.7.5.833. [DOI] [PubMed] [Google Scholar]
  30. McKinney J. D., Cross F. R. FAR1 and the G1 phase specificity of cell cycle arrest by mating factor in Saccharomyces cerevisiae. Mol Cell Biol. 1995 May;15(5):2509–2516. doi: 10.1128/mcb.15.5.2509. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Michaelis S., Herskowitz I. The a-factor pheromone of Saccharomyces cerevisiae is essential for mating. Mol Cell Biol. 1988 Mar;8(3):1309–1318. doi: 10.1128/mcb.8.3.1309. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Oehlen L. J., Cross F. R. G1 cyclins CLN1 and CLN2 repress the mating factor response pathway at Start in the yeast cell cycle. Genes Dev. 1994 May 1;8(9):1058–1070. doi: 10.1101/gad.8.9.1058. [DOI] [PubMed] [Google Scholar]
  33. Osley M. A., Gould J., Kim S., Kane M. Y., Hereford L. Identification of sequences in a yeast histone promoter involved in periodic transcription. Cell. 1986 May 23;45(4):537–544. doi: 10.1016/0092-8674(86)90285-0. [DOI] [PubMed] [Google Scholar]
  34. Peter M., Gartner A., Horecka J., Ammerer G., Herskowitz I. FAR1 links the signal transduction pathway to the cell cycle machinery in yeast. Cell. 1993 May 21;73(4):747–760. doi: 10.1016/0092-8674(93)90254-n. [DOI] [PubMed] [Google Scholar]
  35. Peter M., Herskowitz I. Direct inhibition of the yeast cyclin-dependent kinase Cdc28-Cln by Far1. Science. 1994 Aug 26;265(5176):1228–1231. doi: 10.1126/science.8066461. [DOI] [PubMed] [Google Scholar]
  36. Reid B. J., Hartwell L. H. Regulation of mating in the cell cycle of Saccharomyces cerevisiae. J Cell Biol. 1977 Nov;75(2 Pt 1):355–365. doi: 10.1083/jcb.75.2.355. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Roy A., Lu C. F., Marykwas D. L., Lipke P. N., Kurjan J. The AGA1 product is involved in cell surface attachment of the Saccharomyces cerevisiae cell adhesion glycoprotein a-agglutinin. Mol Cell Biol. 1991 Aug;11(8):4196–4206. doi: 10.1128/mcb.11.8.4196. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Song D., Dolan J. W., Yuan Y. L., Fields S. Pheromone-dependent phosphorylation of the yeast STE12 protein correlates with transcriptional activation. Genes Dev. 1991 May;5(5):741–750. doi: 10.1101/gad.5.5.741. [DOI] [PubMed] [Google Scholar]
  39. Sprague G. F., Jr Assay of yeast mating reaction. Methods Enzymol. 1991;194:77–93. doi: 10.1016/0076-6879(91)94008-z. [DOI] [PubMed] [Google Scholar]
  40. Surana U., Robitsch H., Price C., Schuster T., Fitch I., Futcher A. B., Nasmyth K. The role of CDC28 and cyclins during mitosis in the budding yeast S. cerevisiae. Cell. 1991 Apr 5;65(1):145–161. doi: 10.1016/0092-8674(91)90416-v. [DOI] [PubMed] [Google Scholar]
  41. Tyers M., Futcher B. Far1 and Fus3 link the mating pheromone signal transduction pathway to three G1-phase Cdc28 kinase complexes. Mol Cell Biol. 1993 Sep;13(9):5659–5669. doi: 10.1128/mcb.13.9.5659. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Zanolari B., Riezman H. Quantitation of alpha-factor internalization and response during the Saccharomyces cerevisiae cell cycle. Mol Cell Biol. 1991 Oct;11(10):5251–5258. doi: 10.1128/mcb.11.10.5251. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Zhou Z., Gartner A., Cade R., Ammerer G., Errede B. Pheromone-induced signal transduction in Saccharomyces cerevisiae requires the sequential function of three protein kinases. Mol Cell Biol. 1993 Apr;13(4):2069–2080. doi: 10.1128/mcb.13.4.2069. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. de Koning W., Groeneveld K., Oehlen L. J., Berden J. A., van Dam K. Changes in the activities of key enzymes of glycolysis during the cell cycle in yeast: a rectification. J Gen Microbiol. 1991 Apr;137(4):971–976. doi: 10.1099/00221287-137-4-971. [DOI] [PubMed] [Google Scholar]

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