The yeast Cln3 protein is an unstable activator of Cdc28. (original) (raw)

Mol Cell Biol. 1993 Jun; 13(6): 3266–3271.

Rockefeller University, New York, New York 10021.

Abstract

The Cln3 cyclin homolog of Saccharomyces cerevisiae functions to promote cell cycle START for only a short time following its synthesis. Cln3 protein is highly unstable and is stabilized by C-terminal truncation. Cln3 binds to Cdc28, a protein kinase catalytic subunit essential for cell cycle START, and Cln3 instability requires Cdc28 activity. The long functional lifetime and the hyperactivity of C-terminally truncated Cln3 (Cln3-2) relative to those of full-length Cln3 are affected by mutations in CDC28: the functional lifetime of Cln3-2 is drastically reduced by the cdc28-13 mutation at the permissive temperature, and the cdc28-4 mutation at the permissive temperature completely blocks the function of Cln3-2 while only partially reducing the function of full-length Cln3. Thus, sequences in the C-terminal third of Cln3 might help stabilize functional Cdc28-Cln3 association, as well as decreasing the lifetime of the Cln3 protein. These and other results strongly support the idea that Cln proteins function to activate Cdc28 at START.

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Booher R, Beach D. Involvement of cdc13+ in mitotic control in Schizosaccharomyces pombe: possible interaction of the gene product with microtubules. EMBO J. 1988 Aug;7(8):2321–2327. [PMC free article] [PubMed] [Google Scholar]
Bueno A, Richardson H, Reed SI, Russell P. A fission yeast B-type cyclin functioning early in the cell cycle. Cell. 1991 Jul 12;66(1):149–159. [PubMed] [Google Scholar]
Carter BL, Sudbery PE. Small-sized mutants of Saccharomyces cerevisiae. Genetics. 1980 Nov;96(3):561–566. [PMC free article] [PubMed] [Google Scholar]
Cross F, Roberts J, Weintraub H. Simple and complex cell cycles. Annu Rev Cell Biol. 1989;5:341–396. [PubMed] [Google Scholar]
Cross FR. DAF1, a mutant gene affecting size control, pheromone arrest, and cell cycle kinetics of Saccharomyces cerevisiae. Mol Cell Biol. 1988 Nov;8(11):4675–4684. [PMC free article] [PubMed] [Google Scholar]
Cross FR. Further characterization of a size control gene in Saccharomyces cerevisiae. J Cell Sci Suppl. 1989;12:117–127. [PubMed] [Google Scholar]
Cross FR. Cell cycle arrest caused by CLN gene deficiency in Saccharomyces cerevisiae resembles START-I arrest and is independent of the mating-pheromone signalling pathway. Mol Cell Biol. 1990 Dec;10(12):6482–6490. [PMC free article] [PubMed] [Google Scholar]
Cross FR. CLN- and CDC28-dependent stimulation of CLN1 and CLN2 RNA levels: implications for regulation by alpha-factor and by cell cycle progression. Cold Spring Harb Symp Quant Biol. 1991;56:1–8. [PubMed] [Google Scholar]
Cross FR, Tinkelenberg AH. A potential positive feedback loop controlling CLN1 and CLN2 gene expression at the start of the yeast cell cycle. Cell. 1991 May 31;65(5):875–883. [PubMed] [Google Scholar]
Fang F, Newport JW. Evidence that the G1-S and G2-M transitions are controlled by different cdc2 proteins in higher eukaryotes. Cell. 1991 Aug 23;66(4):731–742. [PubMed] [Google Scholar]
Forsburg SL, Nurse P. Identification of a G1-type cyclin puc1+ in the fission yeast Schizosaccharomyces pombe. Nature. 1991 May 16;351(6323):245–248. [PubMed] [Google Scholar]
Glotzer M, Murray AW, Kirschner MW. Cyclin is degraded by the ubiquitin pathway. Nature. 1991 Jan 10;349(6305):132–138. [PubMed] [Google Scholar]
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] [Google Scholar]
Hartwell LH. Twenty-five years of cell cycle genetics. Genetics. 1991 Dec;129(4):975–980. [PMC free article] [PubMed] [Google Scholar]
Hartwell LH, Culotti J, Pringle JR, Reid BJ. Genetic control of the cell division cycle in yeast. Science. 1974 Jan 11;183(4120):46–51. [PubMed] [Google Scholar]
Ko HA, Moore SA. Kinetic characterization of a prestart cell division control step in yeast. Implications for the mechanism of alpha-factor-induced division arrest. J Biol Chem. 1990 Dec 15;265(35):21652–21663. [PubMed] [Google Scholar]
Koff A, Cross F, Fisher A, Schumacher J, Leguellec K, Philippe M, Roberts JM. Human cyclin E, a new cyclin that interacts with two members of the CDC2 gene family. Cell. 1991 Sep 20;66(6):1217–1228. [PubMed] [Google Scholar]
Lahue EE, Smith AV, Orr-Weaver TL. A novel cyclin gene from Drosophila complements CLN function in yeast. Genes Dev. 1991 Dec;5(12A):2166–2175. [PubMed] [Google Scholar]
Léopold P, O'Farrell PH. An evolutionarily conserved cyclin homolog from Drosophila rescues yeast deficient in G1 cyclins. Cell. 1991 Sep 20;66(6):1207–1216. [PMC free article] [PubMed] [Google Scholar]
Lew DJ, Dulić V, Reed SI. Isolation of three novel human cyclins by rescue of G1 cyclin (Cln) function in yeast. Cell. 1991 Sep 20;66(6):1197–1206. [PubMed] [Google Scholar]
Matsushime H, Roussel MF, Ashmun RA, Sherr CJ. Colony-stimulating factor 1 regulates novel cyclins during the G1 phase of the cell cycle. Cell. 1991 May 17;65(4):701–713. [PubMed] [Google Scholar]
Moore SA. Kinetic evidence for a critical rate of protein synthesis in the Saccharomyces cerevisiae yeast cell cycle. J Biol Chem. 1988 Jul 15;263(20):9674–9681. [PubMed] [Google Scholar]
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] [Google Scholar]
Paris J, Le Guellec R, Couturier A, Le Guellec K, Omilli F, Camonis J, MacNeill S, Philippe M. Cloning by differential screening of a Xenopus cDNA coding for a protein highly homologous to cdc2. Proc Natl Acad Sci U S A. 1991 Feb 1;88(3):1039–1043. [PMC free article] [PubMed] [Google Scholar]
Pines J, Hunter T. Human cyclin A is adenovirus E1A-associated protein p60 and behaves differently from cyclin B. Nature. 1990 Aug 23;346(6286):760–763. [PubMed] [Google Scholar]
Pines J, Hunter T. p34cdc2: the S and M kinase? New Biol. 1990 May;2(5):389–401. [PubMed] [Google Scholar]
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] [Google Scholar]
Rogers S, Wells R, Rechsteiner M. Amino acid sequences common to rapidly degraded proteins: the PEST hypothesis. Science. 1986 Oct 17;234(4774):364–368. [PubMed] [Google Scholar]
Solomon MJ, Glotzer M, Lee TH, Philippe M, Kirschner MW. Cyclin activation of p34cdc2. Cell. 1990 Nov 30;63(5):1013–1024. [PubMed] [Google Scholar]
Tsai LH, Harlow E, Meyerson M. Isolation of the human cdk2 gene that encodes the cyclin A- and adenovirus E1A-associated p33 kinase. Nature. 1991 Sep 12;353(6340):174–177. [PubMed] [Google Scholar]
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] [Google Scholar]
Wilson IA, Niman HL, Houghten RA, Cherenson AR, Connolly ML, Lerner RA. The structure of an antigenic determinant in a protein. Cell. 1984 Jul;37(3):767–778. [PubMed] [Google Scholar]
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] [Google Scholar]
Xiong Y, Connolly T, Futcher B, Beach D. Human D-type cyclin. Cell. 1991 May 17;65(4):691–699. [PubMed] [Google Scholar]

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