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Mol Cell Biol. Dec 1996; 16(12): 6634–6643.
PMCID: PMC231665

Cdc53p acts in concert with Cdc4p and Cdc34p to control the G1-to-S-phase transition and identifies a conserved family of proteins.

Abstract

Regulation of cell cycle progression occurs in part through the targeted degradation of both activating and inhibitory subunits of the cyclin-dependent kinases. During G1, CDC4, encoding a WD-40 repeat protein, and CDC34, encoding a ubiquitin-conjugating enzyme, are involved in the destruction of these regulators. Here we describe evidence indicating that CDC53 also is involved in this process. Mutations in CDC53 cause a phenotype indistinguishable from those of cdc4 and cdc34 mutations, numerous genetic interactions are seen between these genes, and the encoded proteins are found physically associated in vivo. Cdc53p defines a large family of proteins found in yeasts, nematodes, and humans whose molecular functions are uncharacterized. These results suggest a role for this family of proteins in regulating cell cycle proliferation through protein degradation.

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Selected References

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  • Adams AE, Johnson DI, Longnecker RM, Sloat BF, Pringle JR. CDC42 and CDC43, two additional genes involved in budding and the establishment of cell polarity in the yeast Saccharomyces cerevisiae. J Cell Biol. 1990 Jul;111(1):131–142. [PMC free article] [PubMed]
  • Altschul SF, Gish W, Miller W, Myers EW, Lipman DJ. Basic local alignment search tool. J Mol Biol. 1990 Oct 5;215(3):403–410. [PubMed]
  • Banerjee A, Gregori L, Xu Y, Chau V. The bacterially expressed yeast CDC34 gene product can undergo autoubiquitination to form a multiubiquitin chain-linked protein. J Biol Chem. 1993 Mar 15;268(8):5668–5675. [PubMed]
  • Burnatowska-Hledin MA, Spielman WS, Smith WL, Shi P, Meyer JM, Dewitt DL. Expression cloning of an AVP-activated, calcium-mobilizing receptor from rabbit kidney medulla. Am J Physiol. 1995 Jun;268(6 Pt 2):F1198–F1210. [PubMed]
  • Byers B, Goetsch L. Duplication of spindle plaques and integration of the yeast cell cycle. Cold Spring Harb Symp Quant Biol. 1974;38:123–131. [PubMed]
  • Carlson M, Botstein D. Two differentially regulated mRNAs with different 5' ends encode secreted with intracellular forms of yeast invertase. Cell. 1982 Jan;28(1):145–154. [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]
  • Deshaies RJ, Kirschner M. G1 cyclin-dependent activation of p34CDC28 (Cdc28p) in vitro. Proc Natl Acad Sci U S A. 1995 Feb 14;92(4):1182–1186. [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]
  • Goebl MG, Goetsch L, Byers B. The Ubc3 (Cdc34) ubiquitin-conjugating enzyme is ubiquitinated and phosphorylated in vivo. Mol Cell Biol. 1994 May;14(5):3022–3029. [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]
  • Hartwell LH. Macromolecule synthesis in temperature-sensitive mutants of yeast. J Bacteriol. 1967 May;93(5):1662–1670. [PMC free article] [PubMed]
  • Hartwell LH. Genetic control of the cell division cycle in yeast. II. Genes controlling DNA replication and its initiation. J Mol Biol. 1971 Jul 14;59(1):183–194. [PubMed]
  • Henikoff S. Unidirectional digestion with exonuclease III creates targeted breakpoints for DNA sequencing. Gene. 1984 Jun;28(3):351–359. [PubMed]
  • Hochstrasser M. Ubiquitin, proteasomes, and the regulation of intracellular protein degradation. Curr Opin Cell Biol. 1995 Apr;7(2):215–223. [PubMed]
  • Huffaker TC, Hoyt MA, Botstein D. Genetic analysis of the yeast cytoskeleton. Annu Rev Genet. 1987;21:259–284. [PubMed]
  • Huibregtse JM, Scheffner M, Beaudenon S, Howley PM. A family of proteins structurally and functionally related to the E6-AP ubiquitin-protein ligase. Proc Natl Acad Sci U S A. 1995 Mar 28;92(7):2563–2567. [PMC free article] [PubMed]
  • Jentsch S. The ubiquitin-conjugation system. Annu Rev Genet. 1992;26:179–207. [PubMed]
  • Johnson DI, Pringle JR. Molecular characterization of CDC42, a Saccharomyces cerevisiae gene involved in the development of cell polarity. J Cell Biol. 1990 Jul;111(1):143–152. [PMC free article] [PubMed]
  • Kipreos ET, Lander LE, Wing JP, He WW, Hedgecock EM. cul-1 is required for cell cycle exit in C. elegans and identifies a novel gene family. Cell. 1996 Jun 14;85(6):829–839. [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]
  • Koerner TJ, Hill JE, Myers AM, Tzagoloff A. High-expression vectors with multiple cloning sites for construction of trpE fusion genes: pATH vectors. Methods Enzymol. 1991;194:477–490. [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]
  • Liang C, Weinreich M, Stillman B. ORC and Cdc6p interact and determine the frequency of initiation of DNA replication in the genome. Cell. 1995 Jun 2;81(5):667–676. [PubMed]
  • Liu Y, Mathias N, Steussy CN, Goebl MG. Intragenic suppression among CDC34 (UBC3) mutations defines a class of ubiquitin-conjugating catalytic domains. Mol Cell Biol. 1995 Oct;15(10):5635–5644. [PMC free article] [PubMed]
  • McKinney JD, Chang F, Heintz N, Cross FR. Negative regulation of FAR1 at the Start of the yeast cell cycle. Genes Dev. 1993 May;7(5):833–843. [PubMed]
  • Mortimer RK, Schild D, Contopoulou CR, Kans JA. Genetic map of Saccharomyces cerevisiae, edition 10. Yeast. 1989 Sep-Oct;5(5):321–403. [PubMed]
  • Pagano M, Tam SW, Theodoras AM, Beer-Romero P, Del Sal G, Chau V, Yew PR, Draetta GF, Rolfe M. Role of the ubiquitin-proteasome pathway in regulating abundance of the cyclin-dependent kinase inhibitor p27. Science. 1995 Aug 4;269(5224):682–685. [PubMed]
  • Pines J. Cell cycle. Ubiquitin with everything. Nature. 1994 Oct 27;371(6500):742–743. [PubMed]
  • Pringle JR. Staining of bud scars and other cell wall chitin with calcofluor. Methods Enzymol. 1991;194:732–735. [PubMed]
  • Reed SI. The role of p34 kinases in the G1 to S-phase transition. Annu Rev Cell Biol. 1992;8:529–561. [PubMed]
  • Scheffner M, Nuber U, Huibregtse JM. Protein ubiquitination involving an E1-E2-E3 enzyme ubiquitin thioester cascade. Nature. 1995 Jan 5;373(6509):81–83. [PubMed]
  • Schuler GD, Altschul SF, Lipman DJ. A workbench for multiple alignment construction and analysis. Proteins. 1991;9(3):180–190. [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]
  • 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]
  • Sherr CJ. G1 phase progression: cycling on cue. Cell. 1994 Nov 18;79(4):551–555. [PubMed]
  • Sherr CJ, Roberts JM. Inhibitors of mammalian G1 cyclin-dependent kinases. Genes Dev. 1995 May 15;9(10):1149–1163. [PubMed]
  • Struhl K, Stinchcomb DT, Scherer S, Davis RW. High-frequency transformation of yeast: autonomous replication of hybrid DNA molecules. Proc Natl Acad Sci U S A. 1979 Mar;76(3):1035–1039. [PMC free article] [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]
  • 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]
  • 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]
  • Winey M, Goetsch L, Baum P, Byers B. MPS1 and MPS2: novel yeast genes defining distinct steps of spindle pole body duplication. J Cell Biol. 1991 Aug;114(4):745–754. [PMC free article] [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]
  • 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]

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