Skip to main content
NCBI home page
Genetics logoLink to Genetics
. 2003 Nov;165(3):1017–1029. doi: 10.1093/genetics/165.3.1017

The global transcriptional activator of Saccharomyces cerevisiae, Gcr1p, mediates the response to glucose by stimulating protein synthesis and CLN-dependent cell cycle progression.

Kristine A Willis 1, Kellie E Barbara 1, Balaraj B Menon 1, Jason Moffat 1, Brenda Andrews 1, George M Santangelo 1
PMCID: PMC1462843  PMID: 14668361

Abstract

Growth of Saccharomyces cerevisiae requires coordination of cell cycle events (e.g., new cell wall deposition) with constitutive functions like energy generation and duplication of protein mass. The latter processes are stimulated by the phosphoprotein Gcr1p, a transcriptional activator that operates through two different Rap1p-mediated mechanisms to boost expression of glycolytic and ribosomal protein genes, respectively. Simultaneous disruption of both mechanisms results in a loss of glucose responsiveness and a dramatic drop in translation rate. Since a critical rate of protein synthesis (CRPS) is known to mediate passage through Start and determine cell size by modulating levels of Cln3p, we hypothesized that GCR1 regulates cell cycle progression by coordinating it with growth. We therefore constructed and analyzed gcr1delta cln3delta and gcr1delta cln1delta cln2delta strains. Both strains are temperature and cold sensitive; interestingly, they exhibit different arrest phenotypes. The gcr1delta cln3delta strain becomes predominantly unbudded with 1N DNA content (G1 arrest), whereas gcr1delta cln1delta cln2delta cells exhibit severe elongation and apparent M phase arrest. Further analysis demonstrated that the Rap1p/Gcr1p complex mediates rapid growth in glucose by stimulating both cellular metabolism and CLN transcription.

Full Text

The Full Text of this article is available as a PDF (359.1 KB).

Selected References

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

  1. Amon A., Irniger S., Nasmyth K. Closing the cell cycle circle in yeast: G2 cyclin proteolysis initiated at mitosis persists until the activation of G1 cyclins in the next cycle. Cell. 1994 Jul 1;77(7):1037–1050. doi: 10.1016/0092-8674(94)90443-x. [DOI] [PubMed] [Google Scholar]
  2. Anthony C., Zong Q., De Benedetti A. Overexpression of eIF4E in Saccharomyces cerevisiae causes slow growth and decreased alpha-factor response through alterations in CLN3 expression. J Biol Chem. 2001 Jul 30;276(43):39645–39652. doi: 10.1074/jbc.M101564200. [DOI] [PubMed] [Google Scholar]
  3. Ashe M. P., Slaven J. W., De Long S. K., Ibrahimo S., Sachs A. B. A novel eIF2B-dependent mechanism of translational control in yeast as a response to fusel alcohols. EMBO J. 2001 Nov 15;20(22):6464–6474. doi: 10.1093/emboj/20.22.6464. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Baroni M. D., Monti P., Alberghina L. Repression of growth-regulated G1 cyclin expression by cyclic AMP in budding yeast. Nature. 1994 Sep 22;371(6495):339–342. doi: 10.1038/371339a0. [DOI] [PubMed] [Google Scholar]
  5. Benton B. K., Tinkelenberg A. H., Jean D., Plump S. D., Cross F. R. Genetic analysis of Cln/Cdc28 regulation of cell morphogenesis in budding yeast. EMBO J. 1993 Dec 15;12(13):5267–5275. doi: 10.1002/j.1460-2075.1993.tb06222.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Bony M., Barre P., Blondin B. Distribution of the flocculation protein, flop, at the cell surface during yeast growth: the availability of flop determines the flocculation level. Yeast. 1998 Jan 15;14(1):25–35. doi: 10.1002/(SICI)1097-0061(19980115)14:1<25::AID-YEA197>3.0.CO;2-C. [DOI] [PubMed] [Google Scholar]
  7. Burke D. J., Church D. Protein synthesis requirements for nuclear division, cytokinesis, and cell separation in Saccharomyces cerevisiae. Mol Cell Biol. 1991 Jul;11(7):3691–3698. doi: 10.1128/mcb.11.7.3691-3698.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Cullen P. J., Sprague G. F., Jr Glucose depletion causes haploid invasive growth in yeast. Proc Natl Acad Sci U S A. 2000 Dec 5;97(25):13619–13624. doi: 10.1073/pnas.240345197. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Cvrcková F., De Virgilio C., Manser E., Pringle J. R., Nasmyth K. Ste20-like protein kinases are required for normal localization of cell growth and for cytokinesis in budding yeast. Genes Dev. 1995 Aug 1;9(15):1817–1830. doi: 10.1101/gad.9.15.1817. [DOI] [PubMed] [Google Scholar]
  10. Cvrcková F., Nasmyth K. Yeast G1 cyclins CLN1 and CLN2 and a GAP-like protein have a role in bud formation. EMBO J. 1993 Dec 15;12(13):5277–5286. doi: 10.1002/j.1460-2075.1993.tb06223.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Danaie P., Altmann M., Hall M. N., Trachsel H., Helliwell S. B. CLN3 expression is sufficient to restore G1-to-S-phase progression in Saccharomyces cerevisiae mutants defective in translation initiation factor eIF4E. Biochem J. 1999 May 15;340(Pt 1):135–141. [PMC free article] [PubMed] [Google Scholar]
  12. Deminoff S. J., Santangelo G. M. Rap1p requires Gcr1p and Gcr2p homodimers to activate ribosomal protein and glycolytic genes, respectively. Genetics. 2001 May;158(1):133–143. doi: 10.1093/genetics/158.1.133. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Deminoff S. J., Tornow J., Santangelo G. M. Unigenic evolution: a novel genetic method localizes a putative leucine zipper that mediates dimerization of the Saccharomyces cerevisiae regulator Gcr1p. Genetics. 1995 Dec;141(4):1263–1274. doi: 10.1093/genetics/141.4.1263. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Dirick L., Böhm T., Nasmyth K. Roles and regulation of Cln-Cdc28 kinases at the start of the cell cycle of Saccharomyces cerevisiae. EMBO J. 1995 Oct 2;14(19):4803–4813. doi: 10.1002/j.1460-2075.1995.tb00162.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Gallego C., Garí E., Colomina N., Herrero E., Aldea M. The Cln3 cyclin is down-regulated by translational repression and degradation during the G1 arrest caused by nitrogen deprivation in budding yeast. EMBO J. 1997 Dec 1;16(23):7196–7206. doi: 10.1093/emboj/16.23.7196. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Hall D. D., Markwardt D. D., Parviz F., Heideman W. Regulation of the Cln3-Cdc28 kinase by cAMP in Saccharomyces cerevisiae. EMBO J. 1998 Aug 3;17(15):4370–4378. doi: 10.1093/emboj/17.15.4370. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Kobayashi O., Yoshimoto H., Sone H. Analysis of the genes activated by the FLO8 gene in Saccharomyces cerevisiae. Curr Genet. 1999 Nov;36(5):256–261. doi: 10.1007/s002940050498. [DOI] [PubMed] [Google Scholar]
  18. Laroche T., Martin S. G., Tsai-Pflugfelder M., Gasser S. M. The dynamics of yeast telomeres and silencing proteins through the cell cycle. J Struct Biol. 2000 Apr;129(2-3):159–174. doi: 10.1006/jsbi.2000.4240. [DOI] [PubMed] [Google Scholar]
  19. Liu H., Styles C. A., Fink G. R. Saccharomyces cerevisiae S288C has a mutation in FLO8, a gene required for filamentous growth. Genetics. 1996 Nov;144(3):967–978. doi: 10.1093/genetics/144.3.967. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. MacKay V. L., Mai B., Waters L., Breeden L. L. Early cell cycle box-mediated transcription of CLN3 and SWI4 contributes to the proper timing of the G(1)-to-S transition in budding yeast. Mol Cell Biol. 2001 Jul;21(13):4140–4148. doi: 10.1128/MCB.21.13.4140-4148.2001. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Masy C. L., Henquinet A., Mestdagh M. M. Flocculation of Saccharomyces cerevisiae: inhibition by sugars. Can J Microbiol. 1992 Dec;38(12):1298–1306. doi: 10.1139/m92-214. [DOI] [PubMed] [Google Scholar]
  22. Measday V., Moore L., Ogas J., Tyers M., Andrews B. The PCL2 (ORFD)-PHO85 cyclin-dependent kinase complex: a cell cycle regulator in yeast. Science. 1994 Nov 25;266(5189):1391–1395. doi: 10.1126/science.7973731. [DOI] [PubMed] [Google Scholar]
  23. Mencía Mario, Moqtaderi Zarmik, Geisberg Joseph V., Kuras Laurent, Struhl Kevin. Activator-specific recruitment of TFIID and regulation of ribosomal protein genes in yeast. Mol Cell. 2002 Apr;9(4):823–833. doi: 10.1016/s1097-2765(02)00490-2. [DOI] [PubMed] [Google Scholar]
  24. Nasmyth K., Dirick L. The role of SWI4 and SWI6 in the activity of G1 cyclins in yeast. Cell. 1991 Sep 6;66(5):995–1013. doi: 10.1016/0092-8674(91)90444-4. [DOI] [PubMed] [Google Scholar]
  25. Ogas J., Andrews B. J., Herskowitz I. Transcriptional activation of CLN1, CLN2, and a putative new G1 cyclin (HCS26) by SWI4, a positive regulator of G1-specific transcription. Cell. 1991 Sep 6;66(5):1015–1026. doi: 10.1016/0092-8674(91)90445-5. [DOI] [PubMed] [Google Scholar]
  26. Parviz F., Heideman W. Growth-independent regulation of CLN3 mRNA levels by nutrients in Saccharomyces cerevisiae. J Bacteriol. 1998 Jan;180(2):225–230. doi: 10.1128/jb.180.2.225-230.1998. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Polymenis M., Schmidt E. V. Coupling of cell division to cell growth by translational control of the G1 cyclin CLN3 in yeast. Genes Dev. 1997 Oct 1;11(19):2522–2531. doi: 10.1101/gad.11.19.2522. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Popolo L., Vanoni M., Alberghina L. Control of the yeast cell cycle by protein synthesis. Exp Cell Res. 1982 Nov;142(1):69–78. doi: 10.1016/0014-4827(82)90410-4. [DOI] [PubMed] [Google Scholar]
  29. Santangelo G. M., Tornow J. Efficient transcription of the glycolytic gene ADH1 and three translational component genes requires the GCR1 product, which can act through TUF/GRF/RAP binding sites. Mol Cell Biol. 1990 Feb;10(2):859–862. doi: 10.1128/mcb.10.2.859-862.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Shen W. C., Green M. R. Yeast TAF(II)145 functions as a core promoter selectivity factor, not a general coactivator. Cell. 1997 Aug 22;90(4):615–624. doi: 10.1016/s0092-8674(00)80523-1. [DOI] [PubMed] [Google Scholar]
  31. Soares E. V., Mota M. Flocculation onset, growth phase, and genealogical age in Saccharomyces cerevisiae. Can J Microbiol. 1996 Jun;42(6):539–547. doi: 10.1139/m96-073. [DOI] [PubMed] [Google Scholar]
  32. Spellman P. T., Sherlock G., Zhang M. Q., Iyer V. R., Anders K., Eisen M. B., Brown P. O., Botstein D., Futcher B. Comprehensive identification of cell cycle-regulated genes of the yeast Saccharomyces cerevisiae by microarray hybridization. Mol Biol Cell. 1998 Dec;9(12):3273–3297. doi: 10.1091/mbc.9.12.3273. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Stuart D., Wittenberg C. CLN3, not positive feedback, determines the timing of CLN2 transcription in cycling cells. Genes Dev. 1995 Nov 15;9(22):2780–2794. doi: 10.1101/gad.9.22.2780. [DOI] [PubMed] [Google Scholar]
  34. Tennyson C. N., Lee J., Andrews B. J. A role for the Pcl9-Pho85 cyclin-cdk complex at the M/G1 boundary in Saccharomyces cerevisiae. Mol Microbiol. 1998 Apr;28(1):69–79. doi: 10.1046/j.1365-2958.1998.00773.x. [DOI] [PubMed] [Google Scholar]
  35. Tornow J., Zeng X., Gao W., Santangelo G. M. GCR1, a transcriptional activator in Saccharomyces cerevisiae, complexes with RAP1 and can function without its DNA binding domain. EMBO J. 1993 Jun;12(6):2431–2437. doi: 10.1002/j.1460-2075.1993.tb05897.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Tyers M., Tokiwa G., Futcher B. Comparison of the Saccharomyces cerevisiae G1 cyclins: Cln3 may be an upstream activator of Cln1, Cln2 and other cyclins. EMBO J. 1993 May;12(5):1955–1968. doi: 10.1002/j.1460-2075.1993.tb05845.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Velculescu V. E., Zhang L., Zhou W., Vogelstein J., Basrai M. A., Bassett D. E., Jr, Hieter P., Vogelstein B., Kinzler K. W. Characterization of the yeast transcriptome. Cell. 1997 Jan 24;88(2):243–251. doi: 10.1016/s0092-8674(00)81845-0. [DOI] [PubMed] [Google Scholar]

Articles from Genetics are provided here courtesy of Oxford University Press

RESOURCES