s cerevisiae cdc28 protein kinase


Summary: A protein kinase encoded by the Saccharomyces cerevisiae CDC28 gene and required for progression from the G1 PHASE to the S PHASE in the CELL CYCLE.

Top Publications

  1. Heichman K, Roberts J. The yeast CDC16 and CDC27 genes restrict DNA replication to once per cell cycle. Cell. 1996;85:39-48 pubmed
    ..CDC16 and CDC27 may contribute to replication control by targeted proteolysis of an S phase initiator. ..
  2. Costanzo M, Schub O, Andrews B. G1 transcription factors are differentially regulated in Saccharomyces cerevisiae by the Swi6-binding protein Stb1. Mol Cell Biol. 2003;23:5064-77 pubmed
    ..Chromatin immunoprecipitation experiments confirm that Stb1 localizes to promoters of MBF-regulated genes. Our data indicate that, contrary to previous models, MBF and SBF have unique components and might be distinctly regulated. ..
  3. Edgington N, Futcher B. Relationship between the function and the location of G1 cyclins in S. cerevisiae. J Cell Sci. 2001;114:4599-611 pubmed
    ..Our data supports the hypothesis that Cln2 and Cln3 have distinct functions and locations, and the specificity of cyclin-dependent kinases is mediated in part by subcellular location. ..
  4. Mendenhall M. An inhibitor of p34CDC28 protein kinase activity from Saccharomyces cerevisiae. Science. 1993;259:216-9 pubmed
    ..The p40 protein bound tightly to p34CDC28 and inhibited the activity of the kinase. The p40 protein may provide another mechanism to regulate p34CDC28 protein kinase activity. ..
  5. Agarwal R, COHEN FIX O. Phosphorylation of the mitotic regulator Pds1/securin by Cdc28 is required for efficient nuclear localization of Esp1/separase. Genes Dev. 2002;16:1371-82 pubmed
    ..Our results uncover a previously unknown mechanism for regulating the Pds1-Esp1 interaction and shed light on a novel role for Cdc28 in promoting the metaphase-to-anaphase transition in budding yeast. ..
  6. Oehlen L, Cross F. G1 cyclins CLN1 and CLN2 repress the mating factor response pathway at Start in the yeast cell cycle. Genes Dev. 1994;8:1058-70 pubmed
    ..The repression at Start of pheromone signaling by Cln1-Cdc28p or Cln2-Cdc28p kinase complexes may contribute to the acquisition of pheromone resistance as cells execute Start. ..
  7. Charles J, Jaspersen S, Tinker Kulberg R, Hwang L, Szidon A, Morgan D. The Polo-related kinase Cdc5 activates and is destroyed by the mitotic cyclin destruction machinery in S. cerevisiae. Curr Biol. 1998;8:497-507 pubmed
    ..We conclude that Cdc5 is a positive regulator of cyclin-specific APC activity in late mitosis. Degradation of Cdc5 in G1 might provide a feedback mechanism by which the APC destroys its activator at the onset of the next cell cycle. ..
  8. Wu C, Leeuw T, Leberer E, Thomas D, Whiteway M. Cell cycle- and Cln2p-Cdc28p-dependent phosphorylation of the yeast Ste20p protein kinase. J Biol Chem. 1998;273:28107-15 pubmed
    ..In cells that express only the Cln2p G1 cyclin, minor overexpression of Ste20p causes aberrant morphology, suggesting a proper coordination of Ste20p and Cln-Cdc28p activity may be required for the control of cell shape. ..
  9. Peter M, Herskowitz I. Direct inhibition of the yeast cyclin-dependent kinase Cdc28-Cln by Far1. Science. 1994;265:1228-31 pubmed
    ..The kinase activity of Cdc28-Cln was directly inhibited by Far1 both in vivo and in vitro, thus demonstrating that Far1 acts at the final step in the alpha-factor response pathway by inhibiting a G1 cyclin-dependent kinase. ..

More Information


  1. Ho Y, Costanzo M, Moore L, Kobayashi R, Andrews B. Regulation of transcription at the Saccharomyces cerevisiae start transition by Stb1, a Swi6-binding protein. Mol Cell Biol. 1999;19:5267-78 pubmed
    ..Our results suggest a role for STB1 in controlling the timing of Start transcription that is revealed in the absence of the G(1) regulator CLN3, and they implicate Stb1 as an in vivo target of G(1)-specific cyclin-dependent kinases. ..
  2. 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;261:1551-7 pubmed
    ..Mbp1 is related to Swi4. Strains deleted for both MBP1 and SWI4 were inviable, demonstrating that transcriptional activation by MBF and SBF has an important role in the transition from G1 to S phase. ..
  3. Tyers M, Futcher B. Far1 and Fus3 link the mating pheromone signal transduction pathway to three G1-phase Cdc28 kinase complexes. Mol Cell Biol. 1993;13:5659-69 pubmed
    ..Thus, we trace a path through which a mitogen-activated protein kinase regulates a Cdc2 kinase. ..
  4. Henderson K, Kee K, Maleki S, Santini P, Keeney S. Cyclin-dependent kinase directly regulates initiation of meiotic recombination. Cell. 2006;125:1321-32 pubmed
    ..We propose that this function of Cdc28 helps to coordinate the events of meiotic prophase with each other and with progression through prophase. ..
  5. Henchoz S, Chi Y, Catarin B, Herskowitz I, Deshaies R, Peter M. Phosphorylation- and ubiquitin-dependent degradation of the cyclin-dependent kinase inhibitor Far1p in budding yeast. Genes Dev. 1997;11:3046-60 pubmed
    ..Our results show that Far1p is regulated by ubiquitin-mediated proteolysis and suggest that phosphorylation of Far1p by the Cdc28p-Clnp kinase is part of the recognition signal for ubiquitination. ..
  6. Miller M, Cross F. Distinct subcellular localization patterns contribute to functional specificity of the Cln2 and Cln3 cyclins of Saccharomyces cerevisiae. Mol Cell Biol. 2000;20:542-55 pubmed
    ..The data presented here support the idea that cyclin function is regulated at the level of subcellular localization and that subcellular localization contributes to the functional specificity of Cln2p and Cln3p. ..
  7. Vodenicharov M, Wellinger R. DNA degradation at unprotected telomeres in yeast is regulated by the CDK1 (Cdc28/Clb) cell-cycle kinase. Mol Cell. 2006;24:127-37 pubmed
    ..These results strongly suggest that after a loss of the telomere capping function, telomere-led genome instability is caused by tightly regulated cellular DNA repair attempts. ..
  8. Kitazono A, Kron S. An essential function of yeast cyclin-dependent kinase Cdc28 maintains chromosome stability. J Biol Chem. 2002;277:48627-34 pubmed
    ..Significantly, these studies implicate Cdc28 and Cak1 in an essential surveillance function required to maintain genetic stability through mitosis. ..
  9. Harvey S, Charlet A, Haas W, Gygi S, Kellogg D. Cdk1-dependent regulation of the mitotic inhibitor Wee1. Cell. 2005;122:407-20 pubmed
    ..Thus, Cdk1 both positively and negatively regulates its own inhibitor. Regulation of the Swe1-Cdk1 complex is likely to play a critical role in controlling the transition into mitosis. ..
  10. Cross F, Archambault V, Miller M, Klovstad M. Testing a mathematical model of the yeast cell cycle. Mol Biol Cell. 2002;13:52-70 pubmed
    ..Thus, the model is a strong but incomplete attempt at a realistic representation of cell cycle control. Constraints of the sort developed here will be important in development of a truly predictive model. ..
  11. Kitazono A, Garza D, Kron S. Mutations in the yeast cyclin-dependent kinase Cdc28 reveal a role in the spindle assembly checkpoint. Mol Genet Genomics. 2003;269:672-84 pubmed
  12. Elsasser S, Lou F, Wang B, Campbell J, Jong A. Interaction between yeast Cdc6 protein and B-type cyclin/Cdc28 kinases. Mol Biol Cell. 1996;7:1723-35 pubmed
    ..Thus, the interaction may have a role in the essential function of Cdc6 in initiation and in restraining mitosis until replication is complete. ..
  13. 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;266:1391-5 pubmed
    ..Because PHO85 and another cyclin-like molecule, PHO80, also take part in inorganic phosphate metabolism, this cdk enzyme may integrate responses to nutritional conditions with the cell cycle. ..
  14. Huertas P, Cortes Ledesma F, Sartori A, Aguilera A, Jackson S. CDK targets Sae2 to control DNA-end resection and homologous recombination. Nature. 2008;455:689-92 pubmed publisher
    ..These findings therefore provide a mechanistic basis for cell-cycle control of DSB repair and highlight the importance of regulating DSB resection. ..
  15. Lin F, Arndt K. The role of Saccharomyces cerevisiae type 2A phosphatase in the actin cytoskeleton and in entry into mitosis. EMBO J. 1995;14:2745-59 pubmed
    ..These results suggest that PP2A is required during G2 for the activation of Clb-Cdc28 kinase complexes for progression into mitosis. ..
  16. Nishizawa M, Kawasumi M, Fujino M, Toh e A. Phosphorylation of sic1, a cyclin-dependent kinase (Cdk) inhibitor, by Cdk including Pho85 kinase is required for its prompt degradation. Mol Biol Cell. 1998;9:2393-405 pubmed
    ..Pho85 and other G1 Cdks appear to phosphorylate Sic1 at different sites in vivo. Thus at least two distinct Cdks can participate in phosphorylation of Sic1 and may therefore regulate progression through G1. ..
  17. Barlow J, Lisby M, Rothstein R. Differential regulation of the cellular response to DNA double-strand breaks in G1. Mol Cell. 2008;30:73-85 pubmed publisher
    ..Together, these results demonstrate that the DNA repair machinery distinguishes between different types of damage in G1, which translates into different modes of checkpoint activation in G1 and S/G2 cells. ..
  18. Mendenhall M, Hodge A. Regulation of Cdc28 cyclin-dependent protein kinase activity during the cell cycle of the yeast Saccharomyces cerevisiae. Microbiol Mol Biol Rev. 1998;62:1191-243 pubmed
    ..Finally, the mechanisms by which environmental stimuli influence Cdc28 activity are summarized. ..
  19. Keaton M, Bardes E, Marquitz A, Freel C, Zyla T, Rudolph J, et al. Differential susceptibility of yeast S and M phase CDK complexes to inhibitory tyrosine phosphorylation. Curr Biol. 2007;17:1181-9 pubmed
    ..In yeast cells, the combination of CKI binding and preferential phosphorylation/dephosphorylation of different B cyclin/CDK complexes renders S phase progression immune from checkpoints acting via CDK tyrosine phosphorylation. ..
  20. Jaspersen S, Charles J, Morgan D. Inhibitory phosphorylation of the APC regulator Hct1 is controlled by the kinase Cdc28 and the phosphatase Cdc14. Curr Biol. 1999;9:227-36 pubmed
    ..Phosphorylation of Hct1 provides a mechanism by which Cdc28 blocks its own inactivation during S phase and early mitosis. Following anaphase, dephosphorylation of Hct1 by Cdc14 may help initiate cyclin destruction. ..
  21. Andrews B, Measday V. The cyclin family of budding yeast: abundant use of a good idea. Trends Genet. 1998;14:66-72 pubmed
    ..The cyclin family of budding yeast is reviewed from a functional perspective with an emphasis on what genetic and biochemical experiments have revealed about cyclin-CDK substrates. ..
  22. Nguyen V, Co C, Li J. Cyclin-dependent kinases prevent DNA re-replication through multiple mechanisms. Nature. 2001;411:1068-73 pubmed
    ..Only when all three inhibitory pathways are disrupted do origins re-initiate DNA replication in G2/M cells. These studies show that each of these three independent mechanisms of regulation is functionally important. ..
  23. Booher R, Deshaies R, Kirschner M. Properties of Saccharomyces cerevisiae wee1 and its differential regulation of p34CDC28 in response to G1 and G2 cyclins. EMBO J. 1993;12:3417-26 pubmed
    ..These results suggest that specific cyclin subunits target p34CDC28 for distinct regulatory controls which may be important for ensuring proper p34CDC28 function during the cell cycle. ..
  24. Jackson L, Reed S, Haase S. Distinct mechanisms control the stability of the related S-phase cyclins Clb5 and Clb6. Mol Cell Biol. 2006;26:2456-66 pubmed
    ..Taken together, these findings suggest that the SCF(Cdc4) ubiquitin ligase complex regulates Clb6 turnover and that the functional differences exhibited by Clb5 and Clb6 arise from the distinct mechanisms controlling their stability. ..
  25. Li S, Makovets S, Matsuguchi T, Blethrow J, Shokat K, Blackburn E. Cdk1-dependent phosphorylation of Cdc13 coordinates telomere elongation during cell-cycle progression. Cell. 2009;136:50-61 pubmed publisher
    ..These results provide a direct mechanistic link between coordination of telomere elongation and cell-cycle progression in vivo. ..
  26. Schwob E, Bohm T, Mendenhall M, Nasmyth K. The B-type cyclin kinase inhibitor p40SIC1 controls the G1 to S transition in S. cerevisiae. Cell. 1994;79:233-44 pubmed
    ..In wild-type cells, p40SIC1 protein appears at the end of mitosis and disappears shortly before S phase. Proteolysis of a cyclin-specific inhibitor of Cdc28 is therefore an essential aspect of the G1 to S phase transition. ..
  27. Espinoza F, Ogas J, Herskowitz I, Morgan D. Cell cycle control by a complex of the cyclin HCS26 (PCL1) and the kinase PHO85. Science. 1994;266:1388-91 pubmed
    ..HCS26 does not associate with CDC28, but instead associates with PHO85, a closely related protein kinase. Thus, budding yeast, like higher eukaryotes, use multiple cdk's in the regulation of cell cycle progression. ..
  28. Peter M, Gartner A, Horecka J, Ammerer G, Herskowitz I. FAR1 links the signal transduction pathway to the cell cycle machinery in yeast. Cell. 1993;73:747-60 pubmed
    ..These results suggest that FAR1 protein is the link between the signaling pathway and the cell cycle machinery. ..
  29. Oehlen L, Cross F. Potential regulation of Ste20 function by the Cln1-Cdc28 and Cln2-Cdc28 cyclin-dependent protein kinases. J Biol Chem. 1998;273:25089-97 pubmed
  30. Lim H, Goh P, Surana U. Spindle pole body separation in Saccharomyces cerevisiae requires dephosphorylation of the tyrosine 19 residue of Cdc28. Mol Cell Biol. 1996;16:6385-97 pubmed
    ..On the basis of these results, we propose that one of the roles of Tyr-19 dephosphorylation is to promote SPB separation. ..
  31. Grandin N, Charbonneau M. Mitotic cyclins regulate telomeric recombination in telomerase-deficient yeast cells. Mol Cell Biol. 2003;23:9162-77 pubmed
    ..They also uncover a functional interaction between Cdc28/Clb2 and MRX during the control of the mitotic cell cycle. ..
  32. Cross F, Blake C. The yeast Cln3 protein is an unstable activator of Cdc28. Mol Cell Biol. 1993;13:3266-71 pubmed
    ..These and other results strongly support the idea that Cln proteins function to activate Cdc28 at START. ..
  33. Verma R, Feldman R, Deshaies R. SIC1 is ubiquitinated in vitro by a pathway that requires CDC4, CDC34, and cyclin/CDK activities. Mol Biol Cell. 1997;8:1427-37 pubmed
    ..The complementary C-terminal segment of SIC1 binds to the S-phase cyclin CLB5, indicating a modular structure for SIC1. ..
  34. Gartner A, Jovanovic A, Jeoung D, Bourlat S, Cross F, Ammerer G. Pheromone-dependent G1 cell cycle arrest requires Far1 phosphorylation, but may not involve inhibition of Cdc28-Cln2 kinase, in vivo. Mol Cell Biol. 1998;18:3681-91 pubmed
    ..Surprisingly, Far1-associated Cdc28-Cln2 complexes are at best moderately inhibited in immunoprecipitation kinase assays, suggesting unconventional inhibitory mechanisms of Far1. ..
  35. Ydenberg C, Rose M. Antagonistic regulation of Fus2p nuclear localization by pheromone signaling and the cell cycle. J Cell Biol. 2009;184:409-22 pubmed publisher
    ..Our results indicate a novel mechanism by which pheromone-induced proteins are regulated during the transition from mitosis to conjugation. ..
  36. Takahata S, Yu Y, Stillman D. The E2F functional analogue SBF recruits the Rpd3(L) HDAC, via Whi5 and Stb1, and the FACT chromatin reorganizer, to yeast G1 cyclin promoters. EMBO J. 2009;28:3378-89 pubmed publisher
    ..Thus, SBF recruits complexes to promoters that either enhance (FACT) or repress (Rpd3L) accessibility to chromatin, and also recruits the kinase that activates START. ..
  37. Deshaies R, Chau V, Kirschner M. Ubiquitination of the G1 cyclin Cln2p by a Cdc34p-dependent pathway. EMBO J. 1995;14:303-12 pubmed
    ..These results provide a molecular framework for G1 cyclin instability and suggest that a multicomponent, regulated pathway specifies the selective ubiquitination of G1 cyclins. ..
  38. Horn P, Carruthers L, Logie C, Hill D, Solomon M, Wade P, et al. Phosphorylation of linker histones regulates ATP-dependent chromatin remodeling enzymes. Nat Struct Biol. 2002;9:263-7 pubmed
    ..These results suggest that linker histones exert a global, genome-wide control over remodeling activities, implicating a new, obligatory coupling between linker histone kinases and ATP-dependent remodeling enzymes. ..
  39. Breeden L, Mikesell G. Three independent forms of regulation affect expression of HO, CLN1 and CLN2 during the cell cycle of Saccharomyces cerevisiae. Genetics. 1994;138:1015-24 pubmed
    ..This reveals a third source of cell cycle control, which could affect SwI4 activity post-transcriptionally, or reflect the existence of another unidentified regulator of these promoters. ..
  40. Li Y, Elledge S. The DASH complex component Ask1 is a cell cycle-regulated Cdk substrate in Saccharomyces cerevisiae. Cell Cycle. 2003;2:143-8 pubmed
    ..Thus, the DASH complex is directly regulated by cyclin-dependent kinases to facilitate chromosome segregation. ..
  41. Deshaies R, Kirschner M. G1 cyclin-dependent activation of p34CDC28 (Cdc28p) in vitro. Proc Natl Acad Sci U S A. 1995;92:1182-6 pubmed
  42. Kurat C, Wolinski H, Petschnigg J, Kaluarachchi S, Andrews B, Natter K, et al. Cdk1/Cdc28-dependent activation of the major triacylglycerol lipase Tgl4 in yeast links lipolysis to cell-cycle progression. Mol Cell. 2009;33:53-63 pubmed publisher
    ..Our data provide evidence for a direct link between cell-cycle-regulatory kinases and TG degradation and suggest a general mechanism for coordinating membrane synthesis with cell-cycle progression. ..
  43. Barral Y, Parra M, Bidlingmaier S, Snyder M. Nim1-related kinases coordinate cell cycle progression with the organization of the peripheral cytoskeleton in yeast. Genes Dev. 1999;13:176-87 pubmed
    ..Moreover, Hsl1, Kcc4, and Gin4 have homologs in higher eukaryotes, suggesting that the regulation of Swe1/Wee1 by this class of kinases is highly conserved. ..
  44. Farrell A, Morgan D. Cdc37 promotes the stability of protein kinases Cdc28 and Cak1. Mol Cell Biol. 2000;20:749-54 pubmed
    ..We conclude that budding yeast Cdc37, like its higher eukaryotic homologs, promotes the physical integrity of multiple protein kinases, perhaps by virtue of a cotranslational role in protein folding. ..
  45. Crasta K, Huang P, Morgan G, Winey M, Surana U. Cdk1 regulates centrosome separation by restraining proteolysis of microtubule-associated proteins. EMBO J. 2006;25:2551-63 pubmed
  46. Cross F, Levine K. Genetic analysis of the relationship between activation loop phosphorylation and cyclin binding in the activation of the Saccharomyces cerevisiae Cdc28p cyclin-dependent kinase. Genetics. 2000;154:1549-59 pubmed
    ..This conclusion was supported by analysis of suppressors of a mutation in the Cdk phosphothreonine-binding pocket created by cyclin binding. ..
  47. Honey S, Schneider B, Schieltz D, Yates J, Futcher B. A novel multiple affinity purification tag and its use in identification of proteins associated with a cyclin-CDK complex. Nucleic Acids Res. 2001;29:E24 pubmed
    ..Associated proteins were identified using mass spectrometry. These included the known associated proteins Cdc28, Sic1 and Cks1. Several other proteins were found including the 70 kDa chaperone, Ssa1. ..
  48. Janin J, Seraphin B. Genome-wide studies of protein-protein interaction. Curr Opin Struct Biol. 2003;13:383-8 pubmed
    ..In silico methods such as docking simulations, which may contribute to this analysis, are being tested in the CAPRI community-wide experiment, which assesses blind predictions of the structure of protein-protein complexes. ..
  49. Yuste Rojas M, Cross F. Mutations in CDC14 result in high sensitivity to cyclin gene dosage in Saccharomyces cerevisiae. Mol Gen Genet. 2000;263:60-72 pubmed
    ..We also describe genetic interactions between CDC28 and CDC14. ..
  50. Blondel M, Galan J, Chi Y, LaFourcade C, Longaretti C, Deshaies R, et al. Nuclear-specific degradation of Far1 is controlled by the localization of the F-box protein Cdc4. EMBO J. 2000;19:6085-97 pubmed
    ..Our results illustrate the importance of subcellular localization of F-box proteins, and provide an example of how an extracellular signal regulates protein stability at the level of substrate localization. ..
  51. Sidorova J, Mikesell G, Breeden L. Cell cycle-regulated phosphorylation of Swi6 controls its nuclear localization. Mol Biol Cell. 1995;6:1641-58 pubmed
    ..Alanine substitution at position 160 allows nuclear entry of Swi6 throughout the cell cycle. GFP fusions with the N-terminal one-third of Swi6 display the same cell cycle-regulated localization as Swi6. ..
  52. Mort Bontemps Soret M, Facca C, Faye G. Physical interaction of Cdc28 with Cdc37 in Saccharomyces cerevisiae. Mol Genet Genomics. 2002;267:447-58 pubmed
    ..This was not the case for the full-length Cdc28 protein. We present models to explain these results. ..
  53. Jensen S, Geymonat M, Johnson A, Segal M, Johnston L. Spatial regulation of the guanine nucleotide exchange factor Lte1 in Saccharomyces cerevisiae. J Cell Sci. 2002;115:4977-91 pubmed
    ..Our data suggest that an intrameric interaction between the N-and C-terminal regions of Lte1 is important for cortex association. ..