• We are sorry, but NCBI web applications do not support your browser and may not function properly. More information
Logo of embojLink to Publisher's site
EMBO J. Dec 1, 1997; 16(23): 7196–7206.
PMCID: PMC1170320

The Cln3 cyclin is down-regulated by translational repression and degradation during the G1 arrest caused by nitrogen deprivation in budding yeast.

Abstract

Nutrients are among the most important trophic factors in all organisms. When deprived of essential nutrients, yeast cells use accumulated reserves to complete the current cycle and arrest in the following G1 phase. We show here that the Cln3 cyclin, which has a key role in the timely activation of SBF (Swi4-Swi6)- and MBF (Mbp1-Swi6)-dependent promoters in late G1, is down-regulated rapidly at a post-transcriptional level in cells deprived of the nitrogen source. In addition to the fact that Cln3 is degraded faster by ubiquitin-dependent mechanisms, we have found that translation of the CLN3 mRNA is repressed approximately 8-fold under nitrogen deprivation conditions. As a consequence, both SBF- and MBF-dependent expression is strongly down-regulated. Mainly because of their transcriptional dependence on SBF, and perhaps with the contribution of similar post-transcriptional mechanisms to those found for Cln3, the G1 cyclins Cln1 and 2 become undetectable in starved cells. The complete loss of Cln cyclins and the sustained presence of the Clb-cyclin kinase inhibitor Sic1 in starved cells may provide the molecular basis for the G1 arrest caused by nitrogen deprivation.

Full Text

The Full Text of this article is available as a PDF (613K).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Amon A, Tyers M, Futcher B, Nasmyth K. Mechanisms that help the yeast cell cycle clock tick: G2 cyclins transcriptionally activate G2 cyclins and repress G1 cyclins. Cell. 1993 Sep 24;74(6):993–1007. [PubMed]
  • 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. [PubMed]
  • Andrews BJ, Herskowitz I. The yeast SWI4 protein contains a motif present in developmental regulators and is part of a complex involved in cell-cycle-dependent transcription. Nature. 1989 Dec 14;342(6251):830–833. [PubMed]
  • Barbet NC, Schneider U, Helliwell SB, Stansfield I, Tuite MF, Hall MN. TOR controls translation initiation and early G1 progression in yeast. Mol Biol Cell. 1996 Jan;7(1):25–42. [PMC free article] [PubMed]
  • Baroni MD, 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. [PubMed]
  • Barral Y, Jentsch S, Mann C. G1 cyclin turnover and nutrient uptake are controlled by a common pathway in yeast. Genes Dev. 1995 Feb 15;9(4):399–409. [PubMed]
  • Benton BK, Tinkelenberg AH, Jean D, Plump SD, Cross FR. Genetic analysis of Cln/Cdc28 regulation of cell morphogenesis in budding yeast. EMBO J. 1993 Dec 15;12(13):5267–5275. [PMC free article] [PubMed]
  • Blondel M, Mann C. G2 cyclins are required for the degradation of G1 cyclins in yeast. Nature. 1996 Nov 21;384(6606):279–282. [PubMed]
  • Burke DJ, Church D. Protein synthesis requirements for nuclear division, cytokinesis, and cell separation in Saccharomyces cerevisiae. Mol Cell Biol. 1991 Jul;11(7):3691–3698. [PMC free article] [PubMed]
  • Cross FR. Starting the cell cycle: what's the point? Curr Opin Cell Biol. 1995 Dec;7(6):790–797. [PubMed]
  • Cross FR, Blake CM. The yeast Cln3 protein is an unstable activator of Cdc28. Mol Cell Biol. 1993 Jun;13(6):3266–3271. [PMC free article] [PubMed]
  • 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. [PMC free article] [PubMed]
  • Di Como CJ, Arndt KT. Nutrients, via the Tor proteins, stimulate the association of Tap42 with type 2A phosphatases. Genes Dev. 1996 Aug 1;10(15):1904–1916. [PubMed]
  • 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. [PMC free article] [PubMed]
  • Epstein CB, Cross FR. CLB5: a novel B cyclin from budding yeast with a role in S phase. Genes Dev. 1992 Sep;6(9):1695–1706. [PubMed]
  • Ewen ME, Sluss HK, Whitehouse LL, Livingston DM. TGF beta inhibition of Cdk4 synthesis is linked to cell cycle arrest. Cell. 1993 Sep 24;74(6):1009–1020. [PubMed]
  • Garí E, Piedrafita L, Aldea M, Herrero E. A set of vectors with a tetracycline-regulatable promoter system for modulated gene expression in Saccharomyces cerevisiae. Yeast. 1997 Jul;13(9):837–848. [PubMed]
  • Gossen M, Bujard H. Tight control of gene expression in mammalian cells by tetracycline-responsive promoters. Proc Natl Acad Sci U S A. 1992 Jun 15;89(12):5547–5551. [PMC free article] [PubMed]
  • Hadwiger JA, Wittenberg C, Richardson HE, de Barros Lopes M, Reed SI. A family of cyclin homologs that control the G1 phase in yeast. Proc Natl Acad Sci U S A. 1989 Aug;86(16):6255–6259. [PMC free article] [PubMed]
  • Hengst L, Reed SI. Translational control of p27Kip1 accumulation during the cell cycle. Science. 1996 Mar 29;271(5257):1861–1864. [PubMed]
  • Herskowitz I. MAP kinase pathways in yeast: for mating and more. Cell. 1995 Jan 27;80(2):187–197. [PubMed]
  • Hinnebusch AG. A hierarchy of trans-acting factors modulates translation of an activator of amino acid biosynthetic genes in Saccharomyces cerevisiae. Mol Cell Biol. 1985 Sep;5(9):2349–2360. [PMC free article] [PubMed]
  • Hubler L, Bradshaw-Rouse J, Heideman W. Connections between the Ras-cyclic AMP pathway and G1 cyclin expression in the budding yeast Saccharomyces cerevisiae. Mol Cell Biol. 1993 Oct;13(10):6274–6282. [PMC free article] [PubMed]
  • Johnston GC, Pringle JR, Hartwell LH. Coordination of growth with cell division in the yeast Saccharomyces cerevisiae. Exp Cell Res. 1977 Mar 1;105(1):79–98. [PubMed]
  • Koch C, Nasmyth K. Cell cycle regulated transcription in yeast. Curr Opin Cell Biol. 1994 Jun;6(3):451–459. [PubMed]
  • Koch C, Moll T, Neuberg M, Ahorn H, Nasmyth K. A role for the transcription factors Mbp1 and Swi4 in progression from G1 to S phase. Science. 1993 Sep 17;261(5128):1551–1557. [PubMed]
  • Koch C, Schleiffer A, Ammerer G, Nasmyth K. Switching transcription on and off during the yeast cell cycle: Cln/Cdc28 kinases activate bound transcription factor SBF (Swi4/Swi6) at start, whereas Clb/Cdc28 kinases displace it from the promoter in G2. Genes Dev. 1996 Jan 15;10(2):129–141. [PubMed]
  • Lanker S, Valdivieso MH, Wittenberg C. Rapid degradation of the G1 cyclin Cln2 induced by CDK-dependent phosphorylation. Science. 1996 Mar 15;271(5255):1597–1601. [PubMed]
  • Lee KS, Hines LK, Levin DE. A pair of functionally redundant yeast genes (PPZ1 and PPZ2) encoding type 1-related protein phosphatases function within the PKC1-mediated pathway. Mol Cell Biol. 1993 Sep;13(9):5843–5853. [PMC free article] [PubMed]
  • Levine K, Huang K, Cross FR. Saccharomyces cerevisiae G1 cyclins differ in their intrinsic functional specificities. Mol Cell Biol. 1996 Dec;16(12):6794–6803. [PMC free article] [PubMed]
  • Lowndes NF, Johnson AL, Johnston LH. Coordination of expression of DNA synthesis genes in budding yeast by a cell-cycle regulated trans factor. Nature. 1991 Mar 21;350(6315):247–250. [PubMed]
  • Lowndes NF, Johnson AL, Breeden L, Johnston LH. SWI6 protein is required for transcription of the periodically expressed DNA synthesis genes in budding yeast. Nature. 1992 Jun 11;357(6378):505–508. [PubMed]
  • Markwardt DD, Garrett JM, Eberhardy S, Heideman W. Activation of the Ras/cyclic AMP pathway in the yeast Saccharomyces cerevisiae does not prevent G1 arrest in response to nitrogen starvation. J Bacteriol. 1995 Dec;177(23):6761–6765. [PMC free article] [PubMed]
  • McInerny CJ, Partridge JF, Mikesell GE, Creemer DP, Breeden LL. A novel Mcm1-dependent element in the SWI4, CLN3, CDC6, and CDC47 promoters activates M/G1-specific transcription. Genes Dev. 1997 May 15;11(10):1277–1288. [PubMed]
  • Nash R, Tokiwa G, Anand S, Erickson K, Futcher AB. The WHI1+ gene of Saccharomyces cerevisiae tethers cell division to cell size and is a cyclin homolog. EMBO J. 1988 Dec 20;7(13):4335–4346. [PMC free article] [PubMed]
  • Nasmyth K. At the heart of the budding yeast cell cycle. Trends Genet. 1996 Oct;12(10):405–412. [PubMed]
  • Primig M, Sockanathan S, Auer H, Nasmyth K. Anatomy of a transcription factor important for the start of the cell cycle in Saccharomyces cerevisiae. Nature. 1992 Aug 13;358(6387):593–597. [PubMed]
  • Richardson HE, Wittenberg C, Cross F, Reed SI. An essential G1 function for cyclin-like proteins in yeast. Cell. 1989 Dec 22;59(6):1127–1133. [PubMed]
  • Schwob E, Nasmyth K. CLB5 and CLB6, a new pair of B cyclins involved in DNA replication in Saccharomyces cerevisiae. Genes Dev. 1993 Jul;7(7A):1160–1175. [PubMed]
  • Schwob E, Böhm T, Mendenhall MD, Nasmyth K. The B-type cyclin kinase inhibitor p40SIC1 controls the G1 to S transition in S. cerevisiae. Cell. 1994 Oct 21;79(2):233–244. [PubMed]
  • 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. [PubMed]
  • Sudbery PE, Goodey AR, Carter BL. Genes which control cell proliferation in the yeast Saccharomyces cerevisiae. Nature. 1980 Nov 27;288(5789):401–404. [PubMed]
  • Surana U, Amon A, Dowzer C, McGrew J, Byers B, Nasmyth K. Destruction of the CDC28/CLB mitotic kinase is not required for the metaphase to anaphase transition in budding yeast. EMBO J. 1993 May;12(5):1969–1978. [PMC free article] [PubMed]
  • Tokiwa G, Tyers M, Volpe T, Futcher B. Inhibition of G1 cyclin activity by the Ras/cAMP pathway in yeast. Nature. 1994 Sep 22;371(6495):342–345. [PubMed]
  • 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. [PMC free article] [PubMed]
  • Wach A, Brachat A, Pöhlmann R, Philippsen P. New heterologous modules for classical or PCR-based gene disruptions in Saccharomyces cerevisiae. Yeast. 1994 Dec;10(13):1793–1808. [PubMed]
  • Weiner MP, Costa GL, Schoettlin W, Cline J, Mathur E, Bauer JC. Site-directed mutagenesis of double-stranded DNA by the polymerase chain reaction. Gene. 1994 Dec 30;151(1-2):119–123. [PubMed]
  • Wittenberg C, Sugimoto K, Reed SI. G1-specific cyclins of S. cerevisiae: cell cycle periodicity, regulation by mating pheromone, and association with the p34CDC28 protein kinase. Cell. 1990 Jul 27;62(2):225–237. [PubMed]
  • Yaglom J, Linskens MH, Sadis S, Rubin DM, Futcher B, Finley D. p34Cdc28-mediated control of Cln3 cyclin degradation. Mol Cell Biol. 1995 Feb;15(2):731–741. [PMC free article] [PubMed]

Articles from The EMBO Journal are provided here courtesy of The European Molecular Biology Organization

Formats:

Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...

Links

  • Compound
    Compound
    PubChem Compound links
  • MedGen
    MedGen
    Related information in MedGen
  • PubMed
    PubMed
    PubMed citations for these articles
  • Substance
    Substance
    PubChem Substance links

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...