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EMBO J. Sep 15, 1997; 16(18): 5629–5638.
PMCID: PMC1170195

Grr1 of Saccharomyces cerevisiae is connected to the ubiquitin proteolysis machinery through Skp1: coupling glucose sensing to gene expression and the cell cycle.

Abstract

Grr1 protein of the yeast Saccharomyces cerevisiae is a central component of a glucose signal transduction mechanism responsible for glucose-induced gene expression. It is required for glucose-stimulated regulation of Rgt1, a repressor of several glucose-induced HXT genes. Grr1 also plays a role in regulating the cell cycle, because it is required for degradation of the G1 cyclins Cln1 and Cln2. We discovered that Grr1 physically interacts with Skp1, a protein that has been implicated in a ubiquitin-conjugating enzyme complex that targets for degradation the cell cycle regulators Cln1 and Cln2, and the cyclin-dependent kinase inhibitor Sic1. Thus, Grr1 may regulate the cell cycle and glucose-induced gene expression via ubiquitin-mediated protein degradation. Consistent with this idea, Skp1, like Grr1, was found to be required for glucose-induced HXT gene expression. Two functional domains of Grr1 are required for its interaction with Skp1: 12 leucine-rich repeats (LRR) and an adjacent F-box. The Grr1-Skp1 interaction is enhanced by high levels of glucose. This could provide yeast with a mechanism for coupling nutrient availability to gene expression and cell cycle regulation.

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Selected References

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  • Conklin DS, Kung C, Culbertson MR. The COT2 gene is required for glucose-dependent divalent cation transport in Saccharomyces cerevisiae. Mol Cell Biol. 1993 Apr;13(4):2041–2049. [PMC free article] [PubMed]
  • Connelly C, Hieter P. Budding yeast SKP1 encodes an evolutionarily conserved kinetochore protein required for cell cycle progression. Cell. 1996 Jul 26;86(2):275–285. [PubMed]
  • Deshaies RJ, Chau V, Kirschner M. Ubiquitination of the G1 cyclin Cln2p by a Cdc34p-dependent pathway. EMBO J. 1995 Jan 16;14(2):303–312. [PMC free article] [PubMed]
  • Durfee T, Becherer K, Chen PL, Yeh SH, Yang Y, Kilburn AE, Lee WH, Elledge SJ. The retinoblastoma protein associates with the protein phosphatase type 1 catalytic subunit. Genes Dev. 1993 Apr;7(4):555–569. [PubMed]
  • Erickson JR, Johnston M. Suppressors reveal two classes of glucose repression genes in the yeast Saccharomyces cerevisiae. Genetics. 1994 Apr;136(4):1271–1278. [PMC free article] [PubMed]
  • Fields S, Song O. A novel genetic system to detect protein-protein interactions. Nature. 1989 Jul 20;340(6230):245–246. [PubMed]
  • Flick JS, Johnston M. GRR1 of Saccharomyces cerevisiae is required for glucose repression and encodes a protein with leucine-rich repeats. Mol Cell Biol. 1991 Oct;11(10):5101–5112. [PMC free article] [PubMed]
  • Goebl MG, Yochem J, Jentsch S, McGrath JP, Varshavsky A, Byers B. The yeast cell cycle gene CDC34 encodes a ubiquitin-conjugating enzyme. Science. 1988 Sep 9;241(4871):1331–1335. [PubMed]
  • Hardy CF, Pautz A. A novel role for Cdc5p in DNA replication. Mol Cell Biol. 1996 Dec;16(12):6775–6782. [PMC free article] [PubMed]
  • Harper JW, Adami GR, Wei N, Keyomarsi K, Elledge SJ. The p21 Cdk-interacting protein Cip1 is a potent inhibitor of G1 cyclin-dependent kinases. Cell. 1993 Nov 19;75(4):805–816. [PubMed]
  • Hicke L, Riezman H. Ubiquitination of a yeast plasma membrane receptor signals its ligand-stimulated endocytosis. Cell. 1996 Jan 26;84(2):277–287. [PubMed]
  • Hochstrasser M. Ubiquitin, proteasomes, and the regulation of intracellular protein degradation. Curr Opin Cell Biol. 1995 Apr;7(2):215–223. [PubMed]
  • Hochstrasser M. Protein degradation or regulation: Ub the judge. Cell. 1996 Mar 22;84(6):813–815. [PubMed]
  • Jackson PK. Cell cycle: cull and destroy. Curr Biol. 1996 Oct 1;6(10):1209–1212. [PubMed]
  • Kim YJ, Francisco L, Chen GC, Marcotte E, Chan CS. Control of cellular morphogenesis by the Ip12/Bem2 GTPase-activating protein: possible role of protein phosphorylation. J Cell Biol. 1994 Dec;127(5):1381–1394. [PMC free article] [PubMed]
  • King RW, Deshaies RJ, Peters JM, Kirschner MW. How proteolysis drives the cell cycle. Science. 1996 Dec 6;274(5293):1652–1659. [PubMed]
  • Kobe B, Deisenhofer J. The leucine-rich repeat: a versatile binding motif. Trends Biochem Sci. 1994 Oct;19(10):415–421. [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]
  • Mathias N, Johnson SL, Winey M, Adams AE, Goetsch L, Pringle JR, Byers B, Goebl MG. Cdc53p acts in concert with Cdc4p and Cdc34p to control the G1-to-S-phase transition and identifies a conserved family of proteins. Mol Cell Biol. 1996 Dec;16(12):6634–6643. [PMC free article] [PubMed]
  • Bai C, Sen P, Hofmann K, Ma L, Goebl M, Harper JW, Elledge SJ. SKP1 connects cell cycle regulators to the ubiquitin proteolysis machinery through a novel motif, the F-box. Cell. 1996 Jul 26;86(2):263–274. [PubMed]
  • Neer EJ, Schmidt CJ, Nambudripad R, Smith TF. The ancient regulatory-protein family of WD-repeat proteins. Nature. 1994 Sep 22;371(6495):297–300. [PubMed]
  • Ozcan S, Johnston M. Three different regulatory mechanisms enable yeast hexose transporter (HXT) genes to be induced by different levels of glucose. Mol Cell Biol. 1995 Mar;15(3):1564–1572. [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]
  • Palombella VJ, Rando OJ, Goldberg AL, Maniatis T. The ubiquitin-proteasome pathway is required for processing the NF-kappa B1 precursor protein and the activation of NF-kappa B. Cell. 1994 Sep 9;78(5):773–785. [PubMed]
  • Printen JA, Sprague GF., Jr Protein-protein interactions in the yeast pheromone response pathway: Ste5p interacts with all members of the MAP kinase cascade. Genetics. 1994 Nov;138(3):609–619. [PMC free article] [PubMed]
  • Christianson TW, Sikorski RS, Dante M, Shero JH, Hieter P. Multifunctional yeast high-copy-number shuttle vectors. Gene. 1992 Jan 2;110(1):119–122. [PubMed]
  • Ronne H. Glucose repression in fungi. Trends Genet. 1995 Jan;11(1):12–17. [PubMed]
  • Salama SR, Hendricks KB, Thorner J. G1 cyclin degradation: the PEST motif of yeast Cln2 is necessary, but not sufficient, for rapid protein turnover. Mol Cell Biol. 1994 Dec;14(12):7953–7966. [PMC free article] [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]
  • 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]
  • Trumbly RJ. Glucose repression in the yeast Saccharomyces cerevisiae. Mol Microbiol. 1992 Jan;6(1):15–21. [PubMed]
  • Tyers M, Tokiwa G, Nash R, Futcher B. The Cln3-Cdc28 kinase complex of S. cerevisiae is regulated by proteolysis and phosphorylation. EMBO J. 1992 May;11(5):1773–1784. [PMC free article] [PubMed]
  • Vallier LG, Coons D, Bisson LF, Carlson M. Altered regulatory responses to glucose are associated with a glucose transport defect in grr1 mutants of Saccharomyces cerevisiae. Genetics. 1994 Apr;136(4):1279–1285. [PMC free article] [PubMed]
  • Willems AR, Lanker S, Patton EE, Craig KL, Nason TF, Mathias N, Kobayashi R, Wittenberg C, Tyers M. Cdc53 targets phosphorylated G1 cyclins for degradation by the ubiquitin proteolytic pathway. Cell. 1996 Aug 9;86(3):453–463. [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]
  • Yochem J, Byers B. Structural comparison of the yeast cell division cycle gene CDC4 and a related pseudogene. J Mol Biol. 1987 May 20;195(2):233–245. [PubMed]
  • Zhang H, Kobayashi R, Galaktionov K, Beach D. p19Skp1 and p45Skp2 are essential elements of the cyclin A-CDK2 S phase kinase. Cell. 1995 Sep 22;82(6):915–925. [PubMed]

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