Skip to main content

Fission yeast Cdc37 is required for multiple cell cycle functions

Molecular Genetics and Genomics volume 271, pages 82–90 (2004)Cite this article

Abstract

The identification of a Schizosaccharomyces pombe homologue of the cdc37 gene is described. The gene product is most similar to the budding yeast homologue, but shows similarity to metazoan Cdc37 proteins, with a region of high similarity at the extreme N-terminus. Gene transplacement experiments in diploid cells followed by tetrad dissection show that the gene is essential. Depletion of the gene product after switching off expression of cdc37 from the regulatable nmt81 promoter results in cessation of growth and division. The cells arrest heterogeneously, with a significant proportion showing mitotic defects; paradoxically, a proportion of the cells show a short-cell phenotype consistent with an advanced cell cycle.

This is a preview of subscription content, access via your institution.

Access options

Buy single article

Instant access to the full article PDF.

43,34 €

Price includes VAT (Finland)
Tax calculation will be finalised during checkout.

Fig 1A, B
Fig 2A, B
Fig 3A–C
Fig. 4A–F

References

  • Alfa C, Fantes P, Hyams J, McLeod M, Warbrick E (1993) Experiments with fission yeast: a laboratory course manual. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y.

    Google Scholar 

  • Aligue R, Akhavanniak H, Russell P (1994) A role for Hsp90 in cell-cycle control—Wee1 tyrosine kinase activity requires interaction with Hsp90. EMBO J 13:6099–6106

    CAS  PubMed  Google Scholar 

  • Chen T, Zhang MQ (1998) Pombe: a gene-finding and exon-intron structure prediction system for fission yeast. Yeast 14:701–710

    CAS  PubMed  Google Scholar 

  • Cutforth T, Rubin GM (1994) Mutations in hsp83 and cdc37 impair signaling by the Sevenless receptor tyrosine kinase in Drosophila. Cell 77:1027–1036

    CAS  PubMed  Google Scholar 

  • Dai K, Kobayashi R, Beach D (1996) Physical interaction of mammalian Cdc37 with Cdk4. J Biol Chem 271:22030–22034

    CAS  PubMed  Google Scholar 

  • Farrell A, Morgan DO (2000) Cdc37 promotes the stability of protein kinases Cdc28 and Cak1. Mol Cell Biol 20:749–754

    CAS  PubMed  Google Scholar 

  • Ferguson J, Ho JY, Peterson TA, Reed SI (1986) Nucleotide sequence of the yeast cell division cycle START genes CDC28, CDC36 , CDC37 , and CDC39, and a structural analysis of the predicted products. Nucleic Acids Res 14:6681–6697

    CAS  PubMed  Google Scholar 

  • Fikes JD, Becker DM, Winston F, Guarente L (1990) Striking conservation of TFIID in Schizosaccharomyces pombe and Saccharomyces cerevisiae. Nature 346:291–294

    CAS  PubMed  Google Scholar 

  • Fisher D, Nurse P (1995) Cyclins of the fission yeast Schizosaccharomyces pombe. Semin Cell Biol 6:73–78

    Article  CAS  PubMed  Google Scholar 

  • Forsburg SL (1993) Comparison of Schizosaccharomyces pombe expression systems. Nucleic Acids Res 21:2955–2956

    CAS  PubMed  Google Scholar 

  • Gerber MR, Farrell A, Deshaies RJ, Herskowitz I, Morgan DO (1995) Cdc37 is required for association of the protein kinase Cdc28 with G1 and mitotic cyclins. Proc Natl Acad Sci USA 92:4651–4655

    CAS  PubMed  Google Scholar 

  • Goes FS, Martin J (2001) Hsp90 chaperone complexes are required for the activity and stability of yeast protein kinases Mik1, Wee1 and Swe1. Eur J Biochem 268:2281–2289

    CAS  PubMed  Google Scholar 

  • Grammatikakis N, Lin JH, Grammatikakis A, Tsichlis PN, Cochran BH (1999) p50 cdc37 acting in concert with Hsp90 is required for Raf-1 function. Mol Cell Biol 19:1661–1672

    CAS  PubMed  Google Scholar 

  • Hagan I, Yanagida M (1997) Evidence for cell cycle-specific, spindle pole body-mediated, nuclear positioning in the fission yeast Schizosaccharomyces pombe. J Cell Sci 110:1851–1866

    CAS  PubMed  Google Scholar 

  • Hunter T, Pines J (1994) Cyclins and cancer II. Cyclin D and CDK inhibitors come of age. Cell 79:573–582

    CAS  PubMed  Google Scholar 

  • Hunter T, Poon RYC (1997) Cdc37: a protein kinase chaperone? Trends Cell Biol 7:157–161

    CAS  Google Scholar 

  • Hunter T, Sefton BW (1980) Transforming gene product of Rous sarcoma virus phosphorylates tyrosine. Proc Natl Acad Sci USA 77:1311–1315

    CAS  PubMed  Google Scholar 

  • Kamath RS, et al (2003) Systematic functional analysis of the Caenorhabditis elegans genome using RNAi. Nature 421:231–237

    Article  CAS  PubMed  Google Scholar 

  • Kimura Y, Rutherford SL, Miyata Y, Yahara I, Freeman BC, Yue L, Morimoto RL, Lindquist S (1997) Cdc37 is a molecular chaperone with specific functions in signal transduction. Genes Dev 11:1775–1785

    CAS  PubMed  Google Scholar 

  • Lange BMH, Rebollo E, Herold A, Gonzalez C (2002) Cdc37 is essential for chromosome segregation and cytokinesis in higher eukaryotes. EMBO J 21:5364–5374

    Article  CAS  PubMed  Google Scholar 

  • Lee P, Rao J, Fliss A, Yang E, Garrett S, Caplan AJ (2002) The Cdc37 protein kinase-binding domain is sufficient for protein kinase activity and cell viability. J Cell Biol 159:1051–1059

    Article  CAS  PubMed  Google Scholar 

  • MacLean M, Picard D (2003) Cdc37 goes beyond Hsp90 and kinases. Cell Stress Chaperones 8:114–119

    CAS  Google Scholar 

  • Maundrell K (1993) Thiamine-repressible expression vectors pREP and pRIP for fission yeast. Gene 123:127–130

    CAS  PubMed  Google Scholar 

  • Moreno S, Klar A, Nurse P (1991) Molecular genetic analysis of fission yeast Schizosaccharomyces pombe. Methods Enzymol 194:795–823

    CAS  PubMed  Google Scholar 

  • Morgan DO (1995) Principles of Cdk regulation. Nature 374:131–134

    CAS  PubMed  Google Scholar 

  • Mort-Bontemps-Soret M, Facca C, Faye G (2002) Physical interaction of Cdc28 with Cdc37 in Saccharomyces cerevisiae. Mol Genet Genomics 267:447–458

    Article  CAS  PubMed  Google Scholar 

  • Munoz MJ, Jimenez J (1999) Genetic interactions between Hsp90 and the Cdc2 mitotic machinery in the fission yeast Schizosaccharomyces pombe. Mol Gen Genet 261:242–250

    PubMed  Google Scholar 

  • Nurse P (1990) Universal control mechanism regulating onset of M-phase. Nature 344:503–508

    CAS  PubMed  Google Scholar 

  • Ohkura H, Hagan IM, Glover DM (1995) The conserved Schizosaccharomyces pombe kinase Plo1, required to form a bipolar spindle, the actin ring, and septum, can drive septum formation in G1 and G1 Cells. Genes Dev 9:1059–1073

    CAS  PubMed  Google Scholar 

  • Perdew GH, Wiegand H, Van den Heuvel JP, Mitchell C, Singh SS (1997) A 50 kilodalton protein associated with raf and pp60 v-src protein kinases is a mammalian homolog of the cell cycle control protein Cdc37. Biochemistry 36:3600–3607

    Article  CAS  PubMed  Google Scholar 

  • Petersen J, Paris J, Willer M, Philippe M, Hagan IM (2001) The S. pombe Aurora-related kinase Ark1 associates with mitotic structures in a stage-dependent manner and is required for chromosome segregation. J Cell Sci 114:4371–4384

    CAS  PubMed  Google Scholar 

  • Prentice HL (1992) High efficiency transformation of Schizosaccharomyces pombe by electroporation. Nucleic Acids Res 20:621–621

    CAS  PubMed  Google Scholar 

  • Rao J, Lee P, Benzeno S, Cardozo C, Albertus J, Robins DM, Caplan AJ (2001) Functional interaction of human Cdc37 with the androgen receptor but not with the glucocorticoid receptor. J Biol Chem 276:5814–5820

    Article  CAS  PubMed  Google Scholar 

  • Reed SI (1980) The selection of S. cerevisiae mutants defective in the START event of cell division. Genetics 95:561–577

    CAS  PubMed  Google Scholar 

  • Sambrook J, Fritsch EF, Maniatis T (1989) Molecular cloning: a laboratory manual (2nd edn). Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y.

    Google Scholar 

  • Siligardi G, Panaretou B, Meyer P, Singh S, Woolfson DN, Piper PW, Pearl LH, Prodromou C (2002) Regulation of Hsp90 ATPase activity by the co-chaperone Cdc37p/p50 cdc37. J Biol Chem 277:20151–20159

    Article  CAS  PubMed  Google Scholar 

  • Stepanova L, Leng XH, Parker SB, Harper JW (1996) Mammalian p50 cdc37 is a protein kinase-targeting subunit of Hsp90 that binds and stabilizes Cdk4. Genes Dev 10:1491–1502

    CAS  PubMed  Google Scholar 

  • Stepanova L, Finegold M, DeMayo F, Schmidt EV, Harper JW (2000a) The oncoprotein kinase chaperone CDC37 functions as an oncogene in mice and collaborates with both c-myc and cyclin D1 in transformation of multiple tissues. Mol Cell Biol 20:4462–4473

    Article  CAS  PubMed  Google Scholar 

  • Stepanova L, Yang G, DeMayo F, Wheeler TM, Finegold M, Thompson TC, Harper JW (2000b) Induction of human Cdc37 in prostate cancer correlates with the ability of targeted Cdc37 expression to promote prostatic hyperplasia. Oncogene 19:2186–2193

    Article  CAS  PubMed  Google Scholar 

  • Tanaka K, Petersen J, MacIver F, Mulvihill DP, Glover DM, Hagan IM (2001) The role of Plo1 kinase in mitotic commitment and septation in Schizosaccharomyces pombe. EMBO J 20:1259–1270

    Article  CAS  PubMed  Google Scholar 

  • Tatebe H, Shiozaki K (2003) Identification of Cdc37 as a novel regulator of the stress-responsive mitogen-activated protein kinase. Mol Cell Biol 23:5132–5142

    Article  CAS  PubMed  Google Scholar 

  • Tommasino M, Maundrell K (1991) Uptake of thiamine by Schizosaccharomyces pombe and its effect as a transcriptional regulator of thiamine-sensitive genes. Curr Genet 20:63–66

    CAS  PubMed  Google Scholar 

  • Yanagida M (1998) Fission yeast cut mutations revisited: control of anaphase. Trends Cell Biol 8:144–149

    CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We thank Joan Davidson for excellent technical support, Hiro Ohkura for advice on cytology, and Andrew Sanderson for FACS analysis. Special thanks are extended to Kazuhiro Shiozaki for communicating unpublished information. We thank the MRC for a studentship to PW, and the BBSRC for a research support grant to PAF. All genetical manipulations described in this paper were carried out in accordance with relevant UK laws and regulations.

Author information

Author notes

  1. P. K. Westwood

    Present address: Molecular Medicine Centre, University of Edinburgh, Western General Hospital, Edinburgh, EH4 2XU, UK

Affiliations

  1. Institute of Cell and Molecular Biology, University of Edinburgh, Mayfield Road, Edinburgh, EH9 3JR, UK

    P. K. Westwood, I. V. Martin & P. A. Fantes

Authors
  1. P. K. Westwood
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. I. V. Martin
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. P. A. Fantes
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to P. A. Fantes.

Additional information

Communicated by D. Y. Thomas

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Westwood, P.K., Martin, I.V. & Fantes, P.A. Fission yeast Cdc37 is required for multiple cell cycle functions. Mol Genet Genomics 271, 82–90 (2004). https://doi.org/10.1007/s00438-003-0958-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00438-003-0958-4

Keywords

  • Fission yeast
  • Cdc37
  • Hsp90
  • Chaperone
  • Cell cycle