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Gene Review

CDC28  -  cyclin-dependent serine/threonine-protein...

Saccharomyces cerevisiae S288c

Synonyms: CDK1, Cell division control protein 28, Cell division protein kinase 1, Cyclin-dependent kinase 1, HSL5, ...
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Disease relevance of CDC28


Psychiatry related information on CDC28


High impact information on CDC28

  • We propose that this function of Cdc28 helps to coordinate the events of meiotic prophase with each other and with progression through prophase [5].
  • Dephosphorylation of Cdk1 leads to further phosphorylation of Swe1 and release of Cdk1 [6].
  • The Wee1 kinase phosphorylates and inhibits cyclin-dependent kinase 1 (Cdk1), thereby delaying entry into mitosis until appropriate conditions have been met [6].
  • Clb4/Cdc28 kinase phosphorylates Kar9 and accumulates on the pole destined to the mother cell [7].
  • Our results indicate that Cdk1-dependent spindle asymmetry ensures proper alignment of the mitotic spindle with the cell division axis [7].

Biological context of CDC28

  • One simple model consistent with the roles of CDC28 and CDC37 in mitosis as well as in caryogamy is that these gene products are structural components of the nucleus that must be built into it during one cell cycle in order to permit successful caryogamy at the next G1 [8].
  • Our results are consistent with CDC28 function being required in both G1 and mitosis [9].
  • We conclude from our results that the KAR1, CDC28, and CDC37 gene products can diffuse between nuclei in a heterocaryon and that they probably perform their function for caryogamy prior to cell fusion [8].
  • An internally deleted nonfunctional cln2 gene was used as a reporter gene to demonstrate that in the absence of mating pheromone, efficient expression of cln2 mRNA requires both an active CDC28 gene and at least one functional CLN gene. mRNA from a nonfunctional cln1 gene was regulated similarly [10].
  • Rescue of this strain by mutant CDC28 was dependent upon the mutant cln2-KAEA, but additional mutagenesis and DNA shuffling yielded multiply mutant CDC28-BYC alleles (bypass of CLNs) that could support highly efficient cell cycle initiation in the complete absence of CLN genes [11].

Anatomical context of CDC28


Associations of CDC28 with chemical compounds


Physical interactions of CDC28

  • Inactivation of the Cln-Cdc28p kinase complex by thermal inactivation of temperature-sensitive Cdc28p prevented repression of FUS1 signaling [22].
  • Although Pho85 is not essential for viability, Pcl1,2-Pho85 kinase complexes become essential for Start in the absence of Cln1,2-Cdc28 kinases [23].
  • In particular, the G2/M transition is initiated by the activity of a complex formed by a CDK of the Cdc2/Cdc28 family and B-type cyclins of the Cdc13/C1b family in the yeasts, Schizosaccharomyces pombe (Sp) and Saccharomyces cerevisiae (Sc) [24].
  • We found that, when separately expressed, the N-terminal lobe of Cdc28 interacted strongly with the C-terminal moiety of Cdc37 in a two-hybrid system [25].
  • We showed recently that a screen for mutant CDC28 with improved binding to a defective Cln2p G1 cyclin yielded a spectrum of mutations similar to those yielded by a screen for intragenic suppressors of the requirement for activation loop phosphorylation (T169E suppressors) [26].

Enzymatic interactions of CDC28

  • We propose that Cdc28p is normally phosphorylated by Cak1p before it binds cyclin [27].
  • Cln3 associates with Cdc28 to form an active kinase complex that phosphorylates Cln3 itself and a co-precipitated substrate of 45 kDa [28].
  • Cdc14p mediates mitotic exit by dephosphorylating Cdk1p substrates and promoting Cdk1p inactivation [29].
  • During vegetative growth, Ste5p is basally phosphorylated through a process regulated by the CDK Cdc28p [30].
  • Two serines near the C-terminus of Cdc3 are phosphorylated in a Cdc28-dependent manner [31].

Regulatory relationships of CDC28

  • Thus, CLN function and CDC28 activity jointly stimulate CLN1 and CLN2 mRNA levels, potentially forming a positive feedback loop for CLN1 and CLN2 expression [10].
  • CAK1 promotes meiosis and spore formation in Saccharomyces cerevisiae in a CDC28-independent fashion [32].
  • Cln2 and Cdc28 subunits coexpressed in baculovirus-infected insect cells fail to exhibit protein kinase activity towards multiple substrates in the absence of Cks1 [33].
  • A Ser-230 to Ala mutation in the consensus sequence (SPIK) recognized by cdc2/CDC28-related kinase in PHO2 protein led to complete loss of its ability to activate the transcription of PHO5 gene [34].
  • Phosphorylation by Cdc28 activates the Cdc20-dependent activity of the anaphase-promoting complex [35].

Other interactions of CDC28

  • The CLN3-2 (DAF1-1) allele prevents both cell cycle arrest and the turnoff of CLN1 and CLN2 mRNAs in response to mating pheromone, but only in the presence of an active CDC28 gene [10].
  • We show here that CLB2 proteolysis, which is important for transition from mitosis to G1, is not confined to a narrow window at the end of mitosis as previously thought but continues until reactivation of CDC28 by CLN cyclins toward the end of the subsequent G1 period [36].
  • Entry into the mitotic cycle (START) requires a protein kinase encoded by the CDC28 gene and one of three redundant G1-specific cyclins encoded by CLN1, -2, and -3 [37].
  • SGV1 encodes a CDC28/cdc2-related kinase required for a G alpha subunit-mediated adaptive response to pheromone in S. cerevisiae [38].
  • The KSS1 gene encodes an apparent protein kinase homologous to the CDC28 (S. cerevisiae) and cdc2+ (S. pombe) gene products [39].
  • A mutant form of a Cdc24-associated protein that fails to undergo Cdk1-dependent phosphorylation causes defects in bud growth [40].

Analytical, diagnostic and therapeutic context of CDC28


  1. Regulation of Saccharomyces cerevisiae CDC7 function during the cell cycle. Yoon, H.J., Loo, S., Campbell, J.L. Mol. Biol. Cell (1993) [Pubmed]
  2. Cytolethal distending toxin demonstrates genotoxic activity in a yeast model. Hassane, D.C., Lee, R.B., Mendenhall, M.D., Pickett, C.L. Infect. Immun. (2001) [Pubmed]
  3. Disjunction of conjoined twins: Cdk1, Cdh1 and separation of centrosomes. Crasta, K., Surana, U. Cell division [electronic resource]. (2006) [Pubmed]
  4. Phosphorylation of tau protein by purified p34cdc28 and a related protein kinase from neurofilaments. Mawal-Dewan, M., Sen, P.C., Abdel-Ghany, M., Shalloway, D., Racker, E. J. Biol. Chem. (1992) [Pubmed]
  5. Cyclin-dependent kinase directly regulates initiation of meiotic recombination. Henderson, K.A., Kee, K., Maleki, S., Santini, P.A., Keeney, S. Cell (2006) [Pubmed]
  6. Cdk1-dependent regulation of the mitotic inhibitor Wee1. Harvey, S.L., Charlet, A., Haas, W., Gygi, S.P., Kellogg, D.R. Cell (2005) [Pubmed]
  7. Asymmetric loading of Kar9 onto spindle poles and microtubules ensures proper spindle alignment. Liakopoulos, D., Kusch, J., Grava, S., Vogel, J., Barral, Y. Cell (2003) [Pubmed]
  8. Genes that act before conjugation to prepare the Saccharomyces cerevisiae nucleus for caryogamy. Dutcher, S.K., Hartwell, L.H. Cell (1983) [Pubmed]
  9. The role of CDC28 and cyclins during mitosis in the budding yeast S. cerevisiae. Surana, U., Robitsch, H., Price, C., Schuster, T., Fitch, I., Futcher, A.B., Nasmyth, K. Cell (1991) [Pubmed]
  10. A potential positive feedback loop controlling CLN1 and CLN2 gene expression at the start of the yeast cell cycle. Cross, F.R., Tinkelenberg, A.H. Cell (1991) [Pubmed]
  11. Directed evolution to bypass cyclin requirements for the Cdc28p cyclin-dependent kinase. Levine, K., Kiang, L., Jacobson, M.D., Fisher, R.P., Cross, F.R. Mol. Cell (1999) [Pubmed]
  12. Inactivation of the cyclin-dependent kinase Cdc28 abrogates cell cycle arrest induced by DNA damage and disassembly of mitotic spindles in Saccharomyces cerevisiae. Li, X., Cai, M. Mol. Cell. Biol. (1997) [Pubmed]
  13. Subcellular localization of a protein kinase required for cell cycle initiation in Saccharomyces cerevisiae: evidence for an association between the CDC28 gene product and the insoluble cytoplasmic matrix. Wittenberg, C., Richardson, S.L., Reed, S.I. J. Cell Biol. (1987) [Pubmed]
  14. Homology probing: identification of cDNA clones encoding members of the protein-serine kinase family. Hanks, S.K. Proc. Natl. Acad. Sci. U.S.A. (1987) [Pubmed]
  15. Cdk1-Clb4 controls the interaction of astral microtubule plus ends with subdomains of the daughter cell cortex. Maekawa, H., Schiebel, E. Genes Dev. (2004) [Pubmed]
  16. Cdk1 regulates centrosome separation by restraining proteolysis of microtubule-associated proteins. Crasta, K., Huang, P., Morgan, G., Winey, M., Surana, U. EMBO J. (2006) [Pubmed]
  17. Catabolite repression mutants of Saccharomyces cerevisiae show altered fermentative metabolism as well as cell cycle behavior in glucose-limited chemostat cultures. Aon, M.A., Cortassa, S. Biotechnol. Bioeng. (1998) [Pubmed]
  18. Regulation by tetracycline of gene expression in Saccharomyces cerevisiae. Nagahashi, S., Nakayama, H., Hamada, K., Yang, H., Arisawa, M., Kitada, K. Mol. Gen. Genet. (1997) [Pubmed]
  19. A search for proteins that interact genetically with histone H3 and H4 amino termini uncovers novel regulators of the Swe1 kinase in Saccharomyces cerevisiae. Ma, X.J., Lu, Q., Grunstein, M. Genes Dev. (1996) [Pubmed]
  20. Phosphorylation- and ubiquitin-dependent degradation of the cyclin-dependent kinase inhibitor Far1p in budding yeast. Henchoz, S., Chi, Y., Catarin, B., Herskowitz, I., Deshaies, R.J., Peter, M. Genes Dev. (1997) [Pubmed]
  21. Molecular evolution allows bypass of the requirement for activation loop phosphorylation of the Cdc28 cyclin-dependent kinase. Cross, F.R., Levine, K. Mol. Cell. Biol. (1998) [Pubmed]
  22. G1 cyclins CLN1 and CLN2 repress the mating factor response pathway at Start in the yeast cell cycle. Oehlen, L.J., Cross, F.R. Genes Dev. (1994) [Pubmed]
  23. A family of cyclin-like proteins that interact with the Pho85 cyclin-dependent kinase. Measday, V., Moore, L., Retnakaran, R., Lee, J., Donoviel, M., Neiman, A.M., Andrews, B. Mol. Cell. Biol. (1997) [Pubmed]
  24. Candida albicans CDK1 and CYB1: cDNA homologues of the cdc2/CDC28 and cdc13/CLB1/CLB2 cell cycle control genes. Damagnez, V., Cottarel, G. Gene (1996) [Pubmed]
  25. Physical interaction of Cdc28 with Cdc37 in Saccharomyces cerevisiae. Mort-Bontemps-Soret, M., Facca, C., Faye, G. Mol. Genet. Genomics (2002) [Pubmed]
  26. Genetic analysis of the relationship between activation loop phosphorylation and cyclin binding in the activation of the Saccharomyces cerevisiae Cdc28p cyclin-dependent kinase. Cross, F.R., Levine, K. Genetics (2000) [Pubmed]
  27. Activating phosphorylation of the Saccharomyces cerevisiae cyclin-dependent kinase, cdc28p, precedes cyclin binding. Ross, K.E., Kaldis, P., Solomon, M.J. Mol. Biol. Cell (2000) [Pubmed]
  28. The Cln3-Cdc28 kinase complex of S. cerevisiae is regulated by proteolysis and phosphorylation. Tyers, M., Tokiwa, G., Nash, R., Futcher, B. EMBO J. (1992) [Pubmed]
  29. The mitotic exit network Mob1p-Dbf2p kinase complex localizes to the nucleus and regulates passenger protein localization. Stoepel, J., Ottey, M.A., Kurischko, C., Hieter, P., Luca, F.C. Mol. Biol. Cell (2005) [Pubmed]
  30. Localized feedback phosphorylation of Ste5p scaffold by associated MAPK cascade. Flotho, A., Simpson, D.M., Qi, M., Elion, E.A. J. Biol. Chem. (2004) [Pubmed]
  31. Phosphorylation of the septin cdc3 in g1 by the cdc28 kinase is essential for efficient septin ring disassembly. Tang, C.S., Reed, S.I. Cell Cycle (2002) [Pubmed]
  32. CAK1 promotes meiosis and spore formation in Saccharomyces cerevisiae in a CDC28-independent fashion. Schaber, M., Lindgren, A., Schindler, K., Bungard, D., Kaldis, P., Winter, E. Mol. Cell. Biol. (2002) [Pubmed]
  33. Cks1 is required for G(1) cyclin-cyclin-dependent kinase activity in budding yeast. Reynard, G.J., Reynolds, W., Verma, R., Deshaies, R.J. Mol. Cell. Biol. (2000) [Pubmed]
  34. Regulation of the yeast transcriptional factor PHO2 activity by phosphorylation. Liu, C., Yang, Z., Yang, J., Xia, Z., Ao, S. J. Biol. Chem. (2000) [Pubmed]
  35. Phosphorylation by Cdc28 activates the Cdc20-dependent activity of the anaphase-promoting complex. Rudner, A.D., Murray, A.W. J. Cell Biol. (2000) [Pubmed]
  36. Closing the cell cycle circle in yeast: G2 cyclin proteolysis initiated at mitosis persists until the activation of G1 cyclins in the next cycle. Amon, A., Irniger, S., Nasmyth, K. Cell (1994) [Pubmed]
  37. The role of SWI4 and SWI6 in the activity of G1 cyclins in yeast. Nasmyth, K., Dirick, L. Cell (1991) [Pubmed]
  38. SGV1 encodes a CDC28/cdc2-related kinase required for a G alpha subunit-mediated adaptive response to pheromone in S. cerevisiae. Irie, K., Nomoto, S., Miyajima, I., Matsumoto, K. Cell (1991) [Pubmed]
  39. A putative protein kinase overcomes pheromone-induced arrest of cell cycling in S. cerevisiae. Courchesne, W.E., Kunisawa, R., Thorner, J. Cell (1989) [Pubmed]
  40. Cdk1 coordinates cell-surface growth with the cell cycle. McCusker, D., Denison, C., Anderson, S., Egelhofer, T.A., Yates, J.R., Gygi, S.P., Kellogg, D.R. Nat. Cell Biol. (2007) [Pubmed]
  41. Sequence analysis of temperature-sensitive mutations in the Saccharomyces cerevisiae gene CDC28. Lörincz, A.T., Reed, S.I. Mol. Cell. Biol. (1986) [Pubmed]
  42. Molecular cloning and analysis of CDC28 and cyclin homologues from the human fungal pathogen Candida albicans. Sherlock, G., Bahman, A.M., Mahal, A., Shieh, J.C., Ferreira, M., Rosamond, J. Mol. Gen. Genet. (1994) [Pubmed]
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