Skip to main content
Log in

Roles of the RAM signaling network in cell cycle progression in Saccharomyces cerevisiae

  • Research Article
  • Published:
Current Genetics Aims and scope Submit manuscript

Abstract

The Saccharomyces cerevisiae Hym1p, Mob2p, Tao3p, Cbk1p, Sog2p and Kic1p proteins are thought to function together in the RAM signaling network, which controls polarized growth, cell separation and cell integrity. Whether these proteins also function as a network to affect cell proliferation is not clear. Here we examined cells lacking or over-expressing RAM components, and evaluated the timing of initiation of DNA replication in each case. Our results suggest opposing roles of RAM proteins, where only Hym1p can promote the transition from the G1 to S phase of the cell cycle. We also uncovered additive growth defects in strains lacking several pair-wise combinations of RAM proteins, possibly arguing for multiple roles of RAM components in the overall control of cell proliferation. Finally, our findings suggest that Hym1p requires the Dcr2p phosphatase to promote the G1/S transition, but it does not require the G1 cyclin Cln3p or the RAS pathway. Taken together, our results point to a complex regulation of cell proliferation by RAM proteins, in a non-uniform manner that was not previously anticipated.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  • Bidlingmaier S, Weiss EL, Seidel C, Drubin DG, Snyder M (2001) The Cbk1p pathway is important for polarized cell growth and cell separation in Saccharomyces cerevisiae. Mol Cell Biol 21:2449–2462

    Article  CAS  PubMed  Google Scholar 

  • Bogomolnaya LM, Pathak R, Guo J, Cham R, Aramayo R, Polymenis M (2004) Hym1p affects cell cycle progression in Saccharomyces cerevisiae. Curr Genet 46:183–192

    Article  CAS  PubMed  Google Scholar 

  • Boudeau J et al (2003) MO25alpha/beta interact with STRADalpha/beta enhancing their ability to bind, activate and localize LKB1 in the cytoplasm. EMBO J 22:5102–5114

    Article  CAS  PubMed  Google Scholar 

  • Colman-Lerner A, Chin TE, Brent R (2001) Yeast Cbk1 and Mob2 activate daughter-specific genetic programs to induce asymmetric cell fates. Cell 107:739–750

    Article  CAS  PubMed  Google Scholar 

  • Cross FR (1988) DAF1, a mutant gene affecting size control, pheromone arrest, and cell cycle kinetics of Saccharomyces cerevisiae. Mol Cell Biol 8:4675–4684

    CAS  PubMed  Google Scholar 

  • Cross FR, Archambault V, Miller M, Klovstad M (2002) Testing a mathematical model of the yeast cell cycle. Mol Biol Cell 13:52–70

    Article  CAS  PubMed  Google Scholar 

  • Dirick L, Bohm T, Nasmyth K (1995) Roles and regulation of Cln-Cdc28 kinases at the start of the cell cycle of Saccharomyces cerevisiae. EMBO J 14:4803–4813

    CAS  PubMed  Google Scholar 

  • Dohrmann PR et al (1992) Parallel pathways of gene regulation: homologous regulators SWI5 and ACE2 differentially control transcription of HO and chitinase. Genes Dev 6:93–104

    Article  CAS  PubMed  Google Scholar 

  • Giaever G et al. (2002) Functional profiling of the Saccharomyces cerevisiae genome. Nature 418:387–391

    Article  CAS  PubMed  Google Scholar 

  • Hall DD, Markwardt DD, Parviz F, Heideman W (1998) Regulation of the Cln3-Cdc28 kinase by cAMP in Saccharomyces cerevisiae. EMBO J 17:4370–4378

    Article  CAS  PubMed  Google Scholar 

  • Hawley SA et al (2003) Complexes between the LKB1 tumor suppressor, STRAD alpha/beta and MO25 alpha/beta are upstream kinases in the AMP-activated protein kinase cascade. J Biol 2:28

    Article  PubMed  Google Scholar 

  • Hemminki A et al (1998) A serine/threonine kinase gene defective in Peutz-Jeghers syndrome. Nature 391:184–187

    Article  CAS  PubMed  Google Scholar 

  • Hong SP, Momcilovic M, Carlson M (2005) Function of mammalian LKB1 and Ca2+/calmodulin-dependent protein kinase kinase alpha as Snf1-activating kinases in yeast. J Biol Chem 280:21804–21809

    Article  CAS  PubMed  Google Scholar 

  • Jenne DE et al (1998) Peutz-Jeghers syndrome is caused by mutations in a novel serine threonine kinase. Nat Genet 18:38–43

    Article  CAS  PubMed  Google Scholar 

  • Jorgensen P et al (2002) High-resolution genetic mapping with ordered arrays of Saccharomyces cerevisiae deletion mutants. Genetics 162:1091–1099

    CAS  PubMed  Google Scholar 

  • Kaiser C, Michaelis S, Mitchell A (1994) Methods in yeast genetics. Cold Spring Harbor Laboratory Press, Cold Spring Harbor

    Google Scholar 

  • Karos M, Fischer R (1996) hymA (hypha-like metulae), a new developmental mutant of Aspergillus nidulans. Microbiology 142:3211–3218

    Article  CAS  PubMed  Google Scholar 

  • Karos M, Fischer R (1999) Molecular characterization of HymA, an evolutionarily highly conserved and highly expressed protein of Aspergillus nidulans. Mol Gen Genet 260:510–521

    Article  CAS  PubMed  Google Scholar 

  • Kurischko C, Weiss G, Ottey M, Luca FC (2005) A role for the Saccharomyces cerevisiae regulation of Ace2 and polarized morphogenesis signaling network in cell integrity. Genetics 171:443–455

    Article  CAS  PubMed  Google Scholar 

  • Laabs TL, Markwardt DD, Slattery MG, Newcomb LL, Stillman DJ, Heideman W (2003) ACE2 is required for daughter cell-specific G1 delay in Saccharomyces cerevisiae. Proc Natl Acad Sci USA 100:10275–10280

    Article  CAS  PubMed  Google Scholar 

  • Lizcano JM et al (2004) LKB1 is a master kinase that activates 13 kinases of the AMPK subfamily, including MARK/PAR-1. EMBO J 23:833–843

    Article  CAS  PubMed  Google Scholar 

  • Longtine MS et al (1998) Additional modules for versatile and economical PCR-based gene deletion and modification in Saccharomyces cerevisiae. Yeast 14:953–961

    Article  CAS  PubMed  Google Scholar 

  • Nash R, Tokiwa G, Anand S, Erickson K, Futcher AB (1988) The WHI1+ gene of Saccharomyces cerevisiae tethers cell division to cell size and is a cyclin homolog. EMBO J 7:4335–4346

    CAS  PubMed  Google Scholar 

  • Nelson B et al (2003) RAM: a conserved signaling network that regulates Ace2p transcriptional activity and polarized morphogenesis. Mol Biol Cell 14:3782–3803

    Article  CAS  PubMed  Google Scholar 

  • Pathak R, Bogomolnaya LM, Guo J, Polymenis M (2004) Gid8p (Dcr1p) and Dcr2p function in a common pathway to promote START completion in Saccharomyces cerevisiae. Eukaryot Cell 3:1627–1638

    Article  CAS  PubMed  Google Scholar 

  • Pringle JR, Hartwell LH (1981) The Saccharomyces cerevisiae cell cycle. In: Strathern JD, Jones EW, Broach JR (eds) The molecular biology of the yeast Saccharomyces. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, pp 97–142

    Google Scholar 

  • Racki WJ, Becam AM, Nasr F, Herbert CJ (2000) Cbk1p, a protein similar to the human myotonic dystrophy kinase, is essential for normal morphogenesis in Saccharomyces cerevisiae. EMBO J 19:4524–4532

    Article  CAS  PubMed  Google Scholar 

  • Regelmann J et al (2003) Catabolite degradation of fructose-1,6-bisphosphatase in the yeast Saccharomyces cerevisiae: a genome-wide screen identifies eight novel GID genes and indicates the existence of two degradation pathways. Mol Biol Cell 14:1652–1663

    Article  CAS  PubMed  Google Scholar 

  • Schneper L, Krauss A, Miyamoto R, Fang S, Broach JR (2004) The Ras/protein kinase a pathway acts in parallel with the Mob2/Cbk1 pathway to effect cell cycle progression and proper bud site selection. Eukaryot Cell 3:108–120

    Article  CAS  PubMed  Google Scholar 

  • Shaw RJ et al (2004) The tumor suppressor LKB1 kinase directly activates AMP-activated kinase and regulates apoptosis in response to energy stress. Proc Natl Acad Sci USA 101:3329–3335

    Article  CAS  PubMed  Google Scholar 

  • Stuart D, Wittenberg C (1995) CLN3, not positive feedback, determines the timing of CLN2 transcription in cycling cells. Genes Dev 9:2780–2794

    Article  CAS  PubMed  Google Scholar 

  • Sudbery PE, Goodey AR, Carter BL (1980) Genes which control cell proliferation in the yeast Saccharomyces cerevisiae. Nature 288:401–404

    Article  CAS  PubMed  Google Scholar 

  • Tyers M, Tokiwa G, Futcher B (1993) Comparison of the Saccharomyces cerevisiae G1 cyclins: Cln3 may be an upstream activator of Cln1, Cln2 and other cyclins. Embo J 12:1955–1968

    CAS  PubMed  Google Scholar 

  • Voth WP, Olsen AE, Sbia M, Freedman KH, Stillman DJ (2005) ACE2, CBK1, and BUD4 in budding and cell separation. Eukaryot Cell 4:1018–1028

    Article  CAS  PubMed  Google Scholar 

  • Weiss EL, Kurischko C, Zhang C, Shokat K, Drubin DG, Luca FC (2002) The Saccharomyces cerevisiae Mob2p-Cbk1p kinase complex promotes polarized growth and acts with the mitotic exit network to facilitate daughter cell-specific localization of Ace2p transcription factor. J Cell Biol 158:885–900

    Article  CAS  PubMed  Google Scholar 

  • Wittenberg C, Reed SI (2005) Cell cycle-dependent transcription in yeast: promoters, transcription factors, and transcriptomes. Oncogene 24:2746–2755

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

We thank F. Cross for the Cln3-PrA strain. We especially want to thank C. Boone for very generously providing us with a large number of ram mutant strains. This work was supported by a grant from the National Institutes of Health (R01-GM062377) to M.P.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Michael Polymenis.

Additional information

Communicated by P. Sunnerhagen

Rights and permissions

Reprints and permissions

About this article

Cite this article

Bogomolnaya, L.M., Pathak, R., Guo, J. et al. Roles of the RAM signaling network in cell cycle progression in Saccharomyces cerevisiae . Curr Genet 49, 384–392 (2006). https://doi.org/10.1007/s00294-006-0069-y

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00294-006-0069-y

Keywords

Navigation