Skip to main content
NCBI home page
Genetics logoLink to Genetics
. 1997 Nov;147(3):1043–1051. doi: 10.1093/genetics/147.3.1043

Mcs4, a Two-Component System Response Regulator Homologue, Regulates the Schizosaccharomyces Pombe Cell Cycle Control

G Cottarel 1
PMCID: PMC1208232  PMID: 9383051

Abstract

The Schizosaccharomyces pombe cdc2-3w wee1-50 double mutant displays a temperature-sensitive lethal phenotype termed mitotic catastrophe. Six mitotic catastrophe suppressor (mcs1-6) genes were identified in a genetic screen designed to identify regulators of cdc2. Mutations in mcs1-6 suppress the cdc2-3w wee1-50 temperature-sensitive growth defect. Here, the cloning of mcs4 is described. The mcs4 gene product displays significant sequence homology to members of the two-component system response regulator protein family. Strains carrying the mcs4 and cdc25 mutations display a synthetic osmotic lethal phenotype along with an inability to grow on minimal synthetic medium. These phenotypes are suppressed by a mutation in wee1. In addition, the wis1 gene, encoding a stress-activated mitogen-activated protein kinase kinase, was identified as a dosage suppressor in this screen. These findings link the two-component signal transduction system to stress response and cell cycle control in S. pombe.

Full Text

The Full Text of this article is available as a PDF (4.2 MB).

Selected References

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

  1. Alex L. A., Borkovich K. A., Simon M. I. Hyphal development in Neurospora crassa: involvement of a two-component histidine kinase. Proc Natl Acad Sci U S A. 1996 Apr 16;93(8):3416–3421. doi: 10.1073/pnas.93.8.3416. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Alex L. A., Simon M. I. Protein histidine kinases and signal transduction in prokaryotes and eukaryotes. Trends Genet. 1994 Apr;10(4):133–138. doi: 10.1016/0168-9525(94)90215-1. [DOI] [PubMed] [Google Scholar]
  3. Altschul S. F., Gish W., Miller W., Myers E. W., Lipman D. J. Basic local alignment search tool. J Mol Biol. 1990 Oct 5;215(3):403–410. doi: 10.1016/S0022-2836(05)80360-2. [DOI] [PubMed] [Google Scholar]
  4. Basi G., Schmid E., Maundrell K. TATA box mutations in the Schizosaccharomyces pombe nmt1 promoter affect transcription efficiency but not the transcription start point or thiamine repressibility. Gene. 1993 Jan 15;123(1):131–136. doi: 10.1016/0378-1119(93)90552-e. [DOI] [PubMed] [Google Scholar]
  5. Bassler B. L., Wright M., Silverman M. R. Multiple signalling systems controlling expression of luminescence in Vibrio harveyi: sequence and function of genes encoding a second sensory pathway. Mol Microbiol. 1994 Jul;13(2):273–286. doi: 10.1111/j.1365-2958.1994.tb00422.x. [DOI] [PubMed] [Google Scholar]
  6. Booher R., Beach D. Interaction between cdc13+ and cdc2+ in the control of mitosis in fission yeast; dissociation of the G1 and G2 roles of the cdc2+ protein kinase. EMBO J. 1987 Nov;6(11):3441–3447. doi: 10.1002/j.1460-2075.1987.tb02667.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Booher R., Beach D. Involvement of cdc13+ in mitotic control in Schizosaccharomyces pombe: possible interaction of the gene product with microtubules. EMBO J. 1988 Aug;7(8):2321–2327. doi: 10.1002/j.1460-2075.1988.tb03075.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Brewster J. L., de Valoir T., Dwyer N. D., Winter E., Gustin M. C. An osmosensing signal transduction pathway in yeast. Science. 1993 Mar 19;259(5102):1760–1763. doi: 10.1126/science.7681220. [DOI] [PubMed] [Google Scholar]
  9. Brown J. L., North S., Bussey H. SKN7, a yeast multicopy suppressor of a mutation affecting cell wall beta-glucan assembly, encodes a product with domains homologous to prokaryotic two-component regulators and to heat shock transcription factors. J Bacteriol. 1993 Nov;175(21):6908–6915. doi: 10.1128/jb.175.21.6908-6915.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Buck V., Russell P., Millar J. B. Identification of a cdk-activating kinase in fission yeast. EMBO J. 1995 Dec 15;14(24):6173–6183. doi: 10.1002/j.1460-2075.1995.tb00308.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Crovello C. S., Furie B. C., Furie B. Histidine phosphorylation of P-selectin upon stimulation of human platelets: a novel pathway for activation-dependent signal transduction. Cell. 1995 Jul 28;82(2):279–286. doi: 10.1016/0092-8674(95)90315-1. [DOI] [PubMed] [Google Scholar]
  12. Dal Santo P., Blanchard B., Hoffman C. S. The Schizosaccharomyces pombe pyp1 protein tyrosine phosphatase negatively regulates nutrient monitoring pathways. J Cell Sci. 1996 Jul;109(Pt 7):1919–1925. doi: 10.1242/jcs.109.7.1919. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Den Haese G. J., Walworth N., Carr A. M., Gould K. L. The Wee1 protein kinase regulates T14 phosphorylation of fission yeast Cdc2. Mol Biol Cell. 1995 Apr;6(4):371–385. doi: 10.1091/mbc.6.4.371. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Ducommun B., Brambilla P., Félix M. A., Franza B. R., Jr, Karsenti E., Draetta G. cdc2 phosphorylation is required for its interaction with cyclin. EMBO J. 1991 Nov;10(11):3311–3319. doi: 10.1002/j.1460-2075.1991.tb04895.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Dunphy W. G. The decision to enter mitosis. Trends Cell Biol. 1994 Jun;4(6):202–207. doi: 10.1016/0962-8924(94)90142-2. [DOI] [PubMed] [Google Scholar]
  16. Galcheva-Gargova Z., Dérijard B., Wu I. H., Davis R. J. An osmosensing signal transduction pathway in mammalian cells. Science. 1994 Aug 5;265(5173):806–808. doi: 10.1126/science.8047888. [DOI] [PubMed] [Google Scholar]
  17. Gould K. L., Moreno S., Owen D. J., Sazer S., Nurse P. Phosphorylation at Thr167 is required for Schizosaccharomyces pombe p34cdc2 function. EMBO J. 1991 Nov;10(11):3297–3309. doi: 10.1002/j.1460-2075.1991.tb04894.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Gould K. L., Nurse P. Tyrosine phosphorylation of the fission yeast cdc2+ protein kinase regulates entry into mitosis. Nature. 1989 Nov 2;342(6245):39–45. doi: 10.1038/342039a0. [DOI] [PubMed] [Google Scholar]
  19. Grimm C., Kohli J., Murray J., Maundrell K. Genetic engineering of Schizosaccharomyces pombe: a system for gene disruption and replacement using the ura4 gene as a selectable marker. Mol Gen Genet. 1988 Dec;215(1):81–86. doi: 10.1007/BF00331307. [DOI] [PubMed] [Google Scholar]
  20. Hagan I., Hayles J., Nurse P. Cloning and sequencing of the cyclin-related cdc13+ gene and a cytological study of its role in fission yeast mitosis. J Cell Sci. 1988 Dec;91(Pt 4):587–595. doi: 10.1242/jcs.91.4.587. [DOI] [PubMed] [Google Scholar]
  21. Henikoff S. Unidirectional digestion with exonuclease III creates targeted breakpoints for DNA sequencing. Gene. 1984 Jun;28(3):351–359. doi: 10.1016/0378-1119(84)90153-7. [DOI] [PubMed] [Google Scholar]
  22. Higgins D. G., Bleasby A. J., Fuchs R. CLUSTAL V: improved software for multiple sequence alignment. Comput Appl Biosci. 1992 Apr;8(2):189–191. doi: 10.1093/bioinformatics/8.2.189. [DOI] [PubMed] [Google Scholar]
  23. Iuchi S., Matsuda Z., Fujiwara T., Lin E. C. The arcB gene of Escherichia coli encodes a sensor-regulator protein for anaerobic repression of the arc modulon. Mol Microbiol. 1990 May;4(5):715–727. doi: 10.1111/j.1365-2958.1990.tb00642.x. [DOI] [PubMed] [Google Scholar]
  24. Kumar S., McLaughlin M. M., McDonnell P. C., Lee J. C., Livi G. P., Young P. R. Human mitogen-activated protein kinase CSBP1, but not CSBP2, complements a hog1 deletion in yeast. J Biol Chem. 1995 Dec 8;270(49):29043–29046. doi: 10.1074/jbc.270.49.29043. [DOI] [PubMed] [Google Scholar]
  25. Lee J. C., Laydon J. T., McDonnell P. C., Gallagher T. F., Kumar S., Green D., McNulty D., Blumenthal M. J., Heys J. R., Landvatter S. W. A protein kinase involved in the regulation of inflammatory cytokine biosynthesis. Nature. 1994 Dec 22;372(6508):739–746. doi: 10.1038/372739a0. [DOI] [PubMed] [Google Scholar]
  26. Lew D. J., Kornbluth S. Regulatory roles of cyclin dependent kinase phosphorylation in cell cycle control. Curr Opin Cell Biol. 1996 Dec;8(6):795–804. doi: 10.1016/s0955-0674(96)80080-9. [DOI] [PubMed] [Google Scholar]
  27. Liao C. H., McCallus D. E., Fett W. F. Molecular characterization of two gene loci required for production of the key pathogenicity factor pectate lyase in Pseudomonas viridiflava. Mol Plant Microbe Interact. 1994 May-Jun;7(3):391–400. doi: 10.1094/mpmi-7-0391. [DOI] [PubMed] [Google Scholar]
  28. Lundgren K., Walworth N., Booher R., Dembski M., Kirschner M., Beach D. mik1 and wee1 cooperate in the inhibitory tyrosine phosphorylation of cdc2. Cell. 1991 Mar 22;64(6):1111–1122. doi: 10.1016/0092-8674(91)90266-2. [DOI] [PubMed] [Google Scholar]
  29. McLeod M., Stein M., Beach D. The product of the mei3+ gene, expressed under control of the mating-type locus, induces meiosis and sporulation in fission yeast. EMBO J. 1987 Mar;6(3):729–736. doi: 10.1002/j.1460-2075.1987.tb04814.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Millar J. B., Buck V., Wilkinson M. G. Pyp1 and Pyp2 PTPases dephosphorylate an osmosensing MAP kinase controlling cell size at division in fission yeast. Genes Dev. 1995 Sep 1;9(17):2117–2130. doi: 10.1101/gad.9.17.2117. [DOI] [PubMed] [Google Scholar]
  31. Millar J. B., Lenaers G., Russell P. Pyp3 PTPase acts as a mitotic inducer in fission yeast. EMBO J. 1992 Dec;11(13):4933–4941. doi: 10.1002/j.1460-2075.1992.tb05600.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Mizukami T., Chang W. I., Garkavtsev I., Kaplan N., Lombardi D., Matsumoto T., Niwa O., Kounosu A., Yanagida M., Marr T. G. A 13 kb resolution cosmid map of the 14 Mb fission yeast genome by nonrandom sequence-tagged site mapping. Cell. 1993 Apr 9;73(1):121–132. doi: 10.1016/0092-8674(93)90165-m. [DOI] [PubMed] [Google Scholar]
  33. Molz L., Booher R., Young P., Beach D. cdc2 and the regulation of mitosis: six interacting mcs genes. Genetics. 1989 Aug;122(4):773–782. doi: 10.1093/genetics/122.4.773. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Moreno S., Klar A., Nurse P. Molecular genetic analysis of fission yeast Schizosaccharomyces pombe. Methods Enzymol. 1991;194:795–823. doi: 10.1016/0076-6879(91)94059-l. [DOI] [PubMed] [Google Scholar]
  35. Morgan D. O. Principles of CDK regulation. Nature. 1995 Mar 9;374(6518):131–134. doi: 10.1038/374131a0. [DOI] [PubMed] [Google Scholar]
  36. Nurse P. Ordering S phase and M phase in the cell cycle. Cell. 1994 Nov 18;79(4):547–550. doi: 10.1016/0092-8674(94)90539-8. [DOI] [PubMed] [Google Scholar]
  37. Ota I. M., Varshavsky A. A yeast protein similar to bacterial two-component regulators. Science. 1993 Oct 22;262(5133):566–569. doi: 10.1126/science.8211183. [DOI] [PubMed] [Google Scholar]
  38. Posas F., Wurgler-Murphy S. M., Maeda T., Witten E. A., Thai T. C., Saito H. Yeast HOG1 MAP kinase cascade is regulated by a multistep phosphorelay mechanism in the SLN1-YPD1-SSK1 "two-component" osmosensor. Cell. 1996 Sep 20;86(6):865–875. doi: 10.1016/s0092-8674(00)80162-2. [DOI] [PubMed] [Google Scholar]
  39. Rothstein R. J. One-step gene disruption in yeast. Methods Enzymol. 1983;101:202–211. doi: 10.1016/0076-6879(83)01015-0. [DOI] [PubMed] [Google Scholar]
  40. Ruis H., Schüller C. Stress signaling in yeast. Bioessays. 1995 Nov;17(11):959–965. doi: 10.1002/bies.950171109. [DOI] [PubMed] [Google Scholar]
  41. Russell P., Nurse P. cdc25+ functions as an inducer in the mitotic control of fission yeast. Cell. 1986 Apr 11;45(1):145–153. doi: 10.1016/0092-8674(86)90546-5. [DOI] [PubMed] [Google Scholar]
  42. Schuster S. C., Noegel A. A., Oehme F., Gerisch G., Simon M. I. The hybrid histidine kinase DokA is part of the osmotic response system of Dictyostelium. EMBO J. 1996 Aug 1;15(15):3880–3889. [PMC free article] [PubMed] [Google Scholar]
  43. Sclafani R. A. Cyclin dependent kinase activating kinases. Curr Opin Cell Biol. 1996 Dec;8(6):788–794. doi: 10.1016/s0955-0674(96)80079-2. [DOI] [PubMed] [Google Scholar]
  44. Shieh J. C., Wilkinson M. G., Buck V., Morgan B. A., Makino K., Millar J. B. The Mcs4 response regulator coordinately controls the stress-activated Wak1-Wis1-Sty1 MAP kinase pathway and fission yeast cell cycle. Genes Dev. 1997 Apr 15;11(8):1008–1022. doi: 10.1101/gad.11.8.1008. [DOI] [PubMed] [Google Scholar]
  45. Shiozaki K., Shiozaki M., Russell P. Mcs4 mitotic catastrophe suppressor regulates the fission yeast cell cycle through the Wik1-Wis1-Spc1 kinase cascade. Mol Biol Cell. 1997 Mar;8(3):409–419. doi: 10.1091/mbc.8.3.409. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. 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]
  47. Solomon M. J., Lee T., Kirschner M. W. Role of phosphorylation in p34cdc2 activation: identification of an activating kinase. Mol Biol Cell. 1992 Jan;3(1):13–27. doi: 10.1091/mbc.3.1.13. [DOI] [PMC free article] [PubMed] [Google Scholar]
  48. Swanson R. V., Alex L. A., Simon M. I. Histidine and aspartate phosphorylation: two-component systems and the limits of homology. Trends Biochem Sci. 1994 Nov;19(11):485–490. doi: 10.1016/0968-0004(94)90135-x. [DOI] [PubMed] [Google Scholar]
  49. Swanson R. V., Simon M. I. Signal transduction. Bringing the eukaryotes up to speed. Curr Biol. 1994 Mar 1;4(3):234–237. doi: 10.1016/s0960-9822(00)00052-x. [DOI] [PubMed] [Google Scholar]
  50. Varshavsky A. The N-end rule. Cell. 1992 May 29;69(5):725–735. doi: 10.1016/0092-8674(92)90285-k. [DOI] [PubMed] [Google Scholar]
  51. Wang N., Shaulsky G., Escalante R., Loomis W. F. A two-component histidine kinase gene that functions in Dictyostelium development. EMBO J. 1996 Aug 1;15(15):3890–3898. [PMC free article] [PubMed] [Google Scholar]
  52. Warbrick E., Fantes P. A. The wis1 protein kinase is a dosage-dependent regulator of mitosis in Schizosaccharomyces pombe. EMBO J. 1991 Dec;10(13):4291–4299. doi: 10.1002/j.1460-2075.1991.tb05007.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  53. Wilkinson J. Q., Lanahan M. B., Yen H. C., Giovannoni J. J., Klee H. J. An ethylene-inducible component of signal transduction encoded by never-ripe. Science. 1995 Dec 15;270(5243):1807–1809. doi: 10.1126/science.270.5243.1807. [DOI] [PubMed] [Google Scholar]
  54. Wright A., Maundrell K., Heyer W. D., Beach D., Nurse P. Vectors for the construction of gene banks and the integration of cloned genes in Schizosaccharomyces pombe and Saccharomyces cerevisiae. Plasmid. 1986 Mar;15(2):156–158. doi: 10.1016/0147-619x(86)90051-x. [DOI] [PubMed] [Google Scholar]
  55. Young P. G., Fantes P. A. Schizosaccharomyces pombe mutants affected in their division response to starvation. J Cell Sci. 1987 Oct;88(Pt 3):295–304. doi: 10.1242/jcs.88.3.295. [DOI] [PubMed] [Google Scholar]

Articles from Genetics are provided here courtesy of Oxford University Press

RESOURCES