Current Genetics

, 49:384 | Cite as

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

  • Lydia M. Bogomolnaya
  • Ritu Pathak
  • Jinbai Guo
  • Michael Polymenis
Research Article

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.

Keywords

HYM1 START MO25 RAM 

Notes

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.

References

  1. 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 21:2449–2462CrossRefPubMedGoogle Scholar
  2. Bogomolnaya LM, Pathak R, Guo J, Cham R, Aramayo R, Polymenis M (2004) Hym1p affects cell cycle progression in Saccharomyces cerevisiae. Curr Genet 46:183–192CrossRefPubMedGoogle Scholar
  3. 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 22:5102–5114CrossRefPubMedGoogle Scholar
  4. Colman-Lerner A, Chin TE, Brent R (2001) Yeast Cbk1 and Mob2 activate daughter-specific genetic programs to induce asymmetric cell fates. Cell 107:739–750CrossRefPubMedGoogle Scholar
  5. Cross FR (1988) DAF1, a mutant gene affecting size control, pheromone arrest, and cell cycle kinetics of Saccharomyces cerevisiae. Mol Cell Biol 8:4675–4684PubMedGoogle Scholar
  6. Cross FR, Archambault V, Miller M, Klovstad M (2002) Testing a mathematical model of the yeast cell cycle. Mol Biol Cell 13:52–70CrossRefPubMedGoogle Scholar
  7. 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 14:4803–4813PubMedGoogle Scholar
  8. Dohrmann PR et al (1992) Parallel pathways of gene regulation: homologous regulators SWI5 and ACE2 differentially control transcription of HO and chitinase. Genes Dev 6:93–104CrossRefPubMedGoogle Scholar
  9. Giaever G et al. (2002) Functional profiling of the Saccharomyces cerevisiae genome. Nature 418:387–391CrossRefPubMedGoogle Scholar
  10. Hall DD, Markwardt DD, Parviz F, Heideman W (1998) Regulation of the Cln3-Cdc28 kinase by cAMP in Saccharomyces cerevisiae. EMBO J 17:4370–4378CrossRefPubMedGoogle Scholar
  11. 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 2:28CrossRefPubMedGoogle Scholar
  12. Hemminki A et al (1998) A serine/threonine kinase gene defective in Peutz-Jeghers syndrome. Nature 391:184–187CrossRefPubMedGoogle Scholar
  13. 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 280:21804–21809CrossRefPubMedGoogle Scholar
  14. Jenne DE et al (1998) Peutz-Jeghers syndrome is caused by mutations in a novel serine threonine kinase. Nat Genet 18:38–43CrossRefPubMedGoogle Scholar
  15. Jorgensen P et al (2002) High-resolution genetic mapping with ordered arrays of Saccharomyces cerevisiae deletion mutants. Genetics 162:1091–1099PubMedGoogle Scholar
  16. Kaiser C, Michaelis S, Mitchell A (1994) Methods in yeast genetics. Cold Spring Harbor Laboratory Press, Cold Spring HarborGoogle Scholar
  17. Karos M, Fischer R (1996) hymA (hypha-like metulae), a new developmental mutant of Aspergillus nidulans. Microbiology 142:3211–3218PubMedCrossRefGoogle Scholar
  18. Karos M, Fischer R (1999) Molecular characterization of HymA, an evolutionarily highly conserved and highly expressed protein of Aspergillus nidulans. Mol Gen Genet 260:510–521CrossRefPubMedGoogle Scholar
  19. 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 171:443–455CrossRefPubMedGoogle Scholar
  20. 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 100:10275–10280CrossRefPubMedGoogle Scholar
  21. Lizcano JM et al (2004) LKB1 is a master kinase that activates 13 kinases of the AMPK subfamily, including MARK/PAR-1. EMBO J 23:833–843CrossRefPubMedGoogle Scholar
  22. Longtine MS et al (1998) Additional modules for versatile and economical PCR-based gene deletion and modification in Saccharomyces cerevisiae. Yeast 14:953–961CrossRefPubMedGoogle Scholar
  23. 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 7:4335–4346PubMedGoogle Scholar
  24. Nelson B et al (2003) RAM: a conserved signaling network that regulates Ace2p transcriptional activity and polarized morphogenesis. Mol Biol Cell 14:3782–3803CrossRefPubMedGoogle Scholar
  25. 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 3:1627–1638CrossRefPubMedGoogle Scholar
  26. 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 97–142Google Scholar
  27. 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 19:4524–4532CrossRefPubMedGoogle Scholar
  28. 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 14:1652–1663CrossRefPubMedGoogle Scholar
  29. 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 3:108–120CrossRefPubMedGoogle Scholar
  30. 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 101:3329–3335CrossRefPubMedGoogle Scholar
  31. Stuart D, Wittenberg C (1995) CLN3, not positive feedback, determines the timing of CLN2 transcription in cycling cells. Genes Dev 9:2780–2794CrossRefPubMedGoogle Scholar
  32. Sudbery PE, Goodey AR, Carter BL (1980) Genes which control cell proliferation in the yeast Saccharomyces cerevisiae. Nature 288:401–404CrossRefPubMedGoogle Scholar
  33. 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 12:1955–1968PubMedGoogle Scholar
  34. Voth WP, Olsen AE, Sbia M, Freedman KH, Stillman DJ (2005) ACE2, CBK1, and BUD4 in budding and cell separation. Eukaryot Cell 4:1018–1028CrossRefPubMedGoogle Scholar
  35. 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 158:885–900CrossRefPubMedGoogle Scholar
  36. Wittenberg C, Reed SI (2005) Cell cycle-dependent transcription in yeast: promoters, transcription factors, and transcriptomes. Oncogene 24:2746–2755CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag 2006

Authors and Affiliations

  • Lydia M. Bogomolnaya
    • 1
  • Ritu Pathak
    • 1
  • Jinbai Guo
    • 1
  • Michael Polymenis
    • 1
  1. 1.Department of Biochemistry and BiophysicsTexas A&M UniversityCollege StationUSA

Personalised recommendations