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Gene Review

CDC24  -  Cdc24p

Saccharomyces cerevisiae S288c

Synonyms: CLS4, Calcium regulatory protein, Cell division control protein 24, YAL041W
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Disease relevance of CDC24

  • In the baculovirus overexpression system which facilitates binding of coexpressed proteins, we now show that XPB binds to the intact BCR protein efficiently but not to CDC24 or Dbl, suggesting specificity of this interaction [1].
  • We report significant sequence similarity between the predicted proto-dbl product and the products of CDC24, a Saccharomyces cerevisiae cell division cycle gene required for correct budding and establishment of cell polarity, and bcr, a gene implicated in the pathogenesis of chronic myelogenous leukemia (CML) [2].
  • Target Bem1p was a doubly-tagged recombinant, Bem1([Asn142-Ile551]), which strongly interacts in ELISA with a C-terminal 75 amino acids polypeptide from Cdc24p exposed on phage [3].

High impact information on CDC24

  • In the organization of the bud site or of the site in which a mating projection appears, Cdc42, its activator Cdc24, and its negative regulators play a fundamental role [4].
  • Cdc24 acts as a guanylyl-nucleotide-exchange factor for the Rho-type GTPase Cdc42, which has been shown to be a fundamental component of the molecular machinery controlling morphogenesis in eukaryotic cells [5].
  • The Ect2 protein has sequence similarity within a central core of 255 amino acids with the products of the breakpoint cluster gene, bcr (ref. 5), the yeast cell cycle gene, CDC24 (ref. 6), and the dbl oncogene [6].
  • A second S. cerevisiae protein, CDC24, which is known from complementation studies to act with CDC42Sc to regulate the development of normal cell shape and the selection of nonrandom budding sites in yeast, contains a region with sequence similarity to the dbl oncogene product [7].
  • In yeast, cells orient polarized growth toward the mating partner along a pheromone gradient by a mechanism that requires Far1p and Cdc24p [8].

Biological context of CDC24

  • Temperature-sensitive cells with mutations of the CDC24 and CDC42 genes, which are incapable of budding and of generating cell polarity at the restrictive temperature, are also unable to mate [5].
  • Mutants defective in gene CDC24, which are unable to bud or establish cell polarity, have been of great interest with regard to both the mechanisms of cellular morphogenesis and the mechanisms that coordinate cell-cycle events [9].
  • Molecular cloning of chromosome I DNA from Saccharomyces cerevisiae: isolation and characterization of the CDC24 gene and adjacent regions of the chromosome [10].
  • Several lines of evidence (including one-step gene replacement experiments) demonstrated that the complementing plasmids contained the bona fide CDC24 and PYK1 genes [10].
  • To extend the genetic map, a copy of the S. cerevisiae URA3 gene was integrated in the outermost cloned region located 32 kb centromere distal to CDC24, and the genetic map distance between these two genes was determined [11].

Anatomical context of CDC24

  • Characterization of synthetic-lethal mutants reveals a role for the Saccharomyces cerevisiae guanine-nucleotide exchange factor Cdc24p in vacuole function and Na+ tolerance [12].
  • These results suggest that formation of a Cdc24p-Far1p-Gbetagamma complex functions as a landmark for orientation of the cytoskeleton during growth towards an external signal [13].
  • Cdc24p, the Saccharomyces cerevisiae GEF for Cdc42p, is found in a particulate fraction and localizes to the plasma membrane [2] [3] at sites of polarized growth [4] [14].
  • Thus, the CDC24 gene product seems to be involved in selection of the budding site, formation of the chitin ring at that site, the subsequent localization of new cell wall growth to the budding site and the growing bud, and the balance between tip growth and uniform growth of the bud that leads to the normal cell shape [15].
  • Here we show that Cdc24, the guanine-nucleotide exchange factor for the yeast GTPase Cdc42, is sequestered in the cell nucleus by Far1 [16].

Associations of CDC24 with chemical compounds

  • CDC24, which is required for bud emergence and encodes a GEF (guanine-nucleotide exchange factor) for the essential Rho-type GTPase Cdc42p, was identified during both screens [17].
  • These PB1 domains harbor either a conserved lysine residue on one side or an acidic OPCA (OPR/PC/AID) motif around the other side; the lysine of p67phox or Bem1p likely binds to the OPCA of p40phox or Cdc24p, respectively, via electrostatic interactions [18].
  • The predicted CLS4 protein was hydrophilic with two serine + threonine-rich domains in the middle and C-terminal regions [19].
  • A calcium-sensitive cls4 mutant of Saccharomyces cerevisiae ceased dividing in the presence of 100 mM CaCl2, producing large, round, unbudded cells [20].

Physical interactions of CDC24

  • The two-hybrid system revealed that Ste4p interacts with Cdc24p [21].
  • Rsr1p/Bud1p binds to the CH-domain of Cdc24p, which is essential for its function in vivo [22].
  • Anchoring was restored by fusing the targeting domain to either the Cdc24p carboxyl-terminal PC domain that interacts with the Bem1p scaffold protein or the Cdc42p KKSKKCTIL membrane-anchoring domain [23].
  • The isolation of one mutation (V44A) correlated with the observations that the T35A effector domain mutation could interfere with Cdc42(D118A, C188S)p-Cdc24p interactions and could suppress the cdc42(D118A) mutation, suggesting that Cdc24p may interact with Cdc42p through its effector domain [24].

Regulatory relationships of CDC24

  • However, one of the other genes that was isolated by virtue of its ability to suppress cdc24 can also suppress cdc42 [25].
  • Although both CDC42 and RSR1 can suppress cdc24 and both appear to encode GTP-binding proteins, these genes do not themselves appear to be functionally interchangeable [25].
  • In addition, Cla4 induces phosphorylation of Cdc24, leading to its dissociation from Bem1 at bud tips, thereby ending polarized bud growth in vivo [26].
  • Cdc24 regulates nuclear shuttling and recruitment of the Ste5 scaffold to a heterotrimeric G protein in Saccharomyces cerevisiae [27].
  • Our results imply that Gbetagamma not only targets Far1p to the correct site but may also trigger a conformational change in Far1p that is required for its ability to activate Cdc24p in vivo [28].
  • Together, our results suggest that Cdc24p oligomerization regulates Cdc42p activation via its localization [29].

Other interactions of CDC24

  • Therefore, the inability of cdc24 and cdc42 mutants to mate has been presumed to be due to a requirement for generation of cell polarity and related morphogenetic events during conjugation [5].
  • The COOH-terminal 75 amino acids of Cdc24p, outside of the GEF domain, can interact with a portion of Bem1p that lacks both SH3 domains [17].
  • The RSR1 gene, which was previously identified as a multicopy suppressor of Ts- mutations in the bud-emergence gene CDC24, encodes a GTPase of the Ras family that is required for both budding patterns [30].
  • Control of the yeast bud-site assembly GTPase Cdc42. Catalysis of guanine nucleotide exchange by Cdc24 and stimulation of GTPase activity by Bem3 [31].
  • MSB2 was identified previously as a multicopy suppressor of a temperature-sensitive mutation in CDC24, a gene required for polarity establishment and bud formation in Saccharomyces cerevisiae [32].

Analytical, diagnostic and therapeutic context of CDC24

  • Electron microscopy of R-loop-containing DNA and RNA blot hybridization analyses indicated that an 18-kb segment contained at least seven transcribed regions, only three of which corresponded to previously known genes (CDC24, PYK1, and CYC3) [10].
  • Further site-directed mutagenesis studies showed that the conserved residue Tyr32 in the putative effector region of both GTPases (numbered by Cdc42Hs) is critical for binding of the GEFs and that specific recognition for Lbc or Cdc24 is achieved at least in part through residues Lys27 of Rho and Gln116 of Cdc42 [33].


  1. BCR binds to the xeroderma pigmentosum group B protein. Maru, Y., Kobayashi, T., Tanaka, K., Shibuya, M. Biochem. Biophys. Res. Commun. (1999) [Pubmed]
  2. A region of proto-dbl essential for its transforming activity shows sequence similarity to a yeast cell cycle gene, CDC24, and the human breakpoint cluster gene, bcr. Ron, D., Zannini, M., Lewis, M., Wickner, R.B., Hunt, L.T., Graziani, G., Tronick, S.R., Aaronson, S.A., Eva, A. New Biol. (1991) [Pubmed]
  3. Whole Genome Phage Display Selects for Proline-rich Boi Polypeptides against Bem1p. Hertveldt, K., Robben, J., Volckaert, G. Biotechnol. Lett. (2006) [Pubmed]
  4. Role of small G proteins in yeast cell polarization and wall biosynthesis. Cabib, E., Drgonová, J., Drgon, T. Annu. Rev. Biochem. (1998) [Pubmed]
  5. Role for the Rho-family GTPase Cdc42 in yeast mating-pheromone signal pathway. Simon, M.N., De Virgilio, C., Souza, B., Pringle, J.R., Abo, A., Reed, S.I. Nature (1995) [Pubmed]
  6. Oncogene ect2 is related to regulators of small GTP-binding proteins. Miki, T., Smith, C.L., Long, J.E., Eva, A., Fleming, T.P. Nature (1993) [Pubmed]
  7. Catalysis of guanine nucleotide exchange on the CDC42Hs protein by the dbl oncogene product. Hart, M.J., Eva, A., Evans, T., Aaronson, S.A., Cerione, R.A. Nature (1991) [Pubmed]
  8. The role of Far1p in linking the heterotrimeric G protein to polarity establishment proteins during yeast mating. Butty, A.C., Pryciak, P.M., Huang, L.S., Herskowitz, I., Peter, M. Science (1998) [Pubmed]
  9. CDC42 and CDC43, two additional genes involved in budding and the establishment of cell polarity in the yeast Saccharomyces cerevisiae. Adams, A.E., Johnson, D.I., Longnecker, R.M., Sloat, B.F., Pringle, J.R. J. Cell Biol. (1990) [Pubmed]
  10. Molecular cloning of chromosome I DNA from Saccharomyces cerevisiae: isolation and characterization of the CDC24 gene and adjacent regions of the chromosome. Coleman, K.G., Steensma, H.Y., Kaback, D.B., Pringle, J.R. Mol. Cell. Biol. (1986) [Pubmed]
  11. Enhanced meiotic recombination on the smallest chromosome of Saccharomyces cerevisiae. Kaback, D.B., Steensma, H.Y., de Jonge, P. Proc. Natl. Acad. Sci. U.S.A. (1989) [Pubmed]
  12. Characterization of synthetic-lethal mutants reveals a role for the Saccharomyces cerevisiae guanine-nucleotide exchange factor Cdc24p in vacuole function and Na+ tolerance. White, W.H., Johnson, D.I. Genetics (1997) [Pubmed]
  13. A Cdc24p-Far1p-Gbetagamma protein complex required for yeast orientation during mating. Nern, A., Arkowitz, R.A. J. Cell Biol. (1999) [Pubmed]
  14. The guanine-nucleotide-exchange factor Cdc24p is targeted to the nucleus and polarized growth sites. Toenjes, K.A., Sawyer, M.M., Johnson, D.I. Curr. Biol. (1999) [Pubmed]
  15. Roles of the CDC24 gene product in cellular morphogenesis during the Saccharomyces cerevisiae cell cycle. Sloat, B.F., Adams, A., Pringle, J.R. J. Cell Biol. (1981) [Pubmed]
  16. Nuclear sequestration of the exchange factor Cdc24 by Far1 regulates cell polarity during yeast mating. Shimada, Y., Gulli, M.P., Peter, M. Nat. Cell Biol. (2000) [Pubmed]
  17. Interactions between the bud emergence proteins Bem1p and Bem2p and Rho-type GTPases in yeast. Peterson, J., Zheng, Y., Bender, L., Myers, A., Cerione, R., Bender, A. J. Cell Biol. (1994) [Pubmed]
  18. Molecular recognition in dimerization between PB1 domains. Noda, Y., Kohjima, M., Izaki, T., Ota, K., Yoshinaga, S., Inagaki, F., Ito, T., Sumimoto, H. J. Biol. Chem. (2003) [Pubmed]
  19. Nucleotide sequence of the CLS4 (CDC24) gene of Saccharomyces cerevisiae. Miyamoto, S., Ohya, Y., Ohsumi, Y., Anraku, Y. Gene (1987) [Pubmed]
  20. Calcium-sensitive cls4 mutant of Saccharomyces cerevisiae with a defect in bud formation. Ohya, Y., Miyamoto, S., Ohsumi, Y., Anraku, Y. J. Bacteriol. (1986) [Pubmed]
  21. Pheromone signalling in Saccharomyces cerevisiae requires the small GTP-binding protein Cdc42p and its activator CDC24. Zhao, Z.S., Leung, T., Manser, E., Lim, L. Mol. Cell. Biol. (1995) [Pubmed]
  22. The nucleotide exchange factor Cdc24p may be regulated by auto-inhibition. Shimada, Y., Wiget, P., Gulli, M.P., Bi, E., Peter, M. EMBO J. (2004) [Pubmed]
  23. Separate membrane targeting and anchoring domains function in the localization of the S. cerevisiae Cdc24p guanine nucleotide exchange factor. Toenjes, K.A., Simpson, D., Johnson, D.I. Curr. Genet. (2004) [Pubmed]
  24. Analysis of the mechanisms of action of the Saccharomyces cerevisiae dominant lethal cdc42G12V and dominant negative cdc42D118A mutations. Davis, C.R., Richman, T.J., Deliduka, S.B., Blaisdell, J.O., Collins, C.C., Johnson, D.I. J. Biol. Chem. (1998) [Pubmed]
  25. Multicopy suppression of the cdc24 budding defect in yeast by CDC42 and three newly identified genes including the ras-related gene RSR1. Bender, A., Pringle, J.R. Proc. Natl. Acad. Sci. U.S.A. (1989) [Pubmed]
  26. Phosphorylation of the Cdc42 exchange factor Cdc24 by the PAK-like kinase Cla4 may regulate polarized growth in yeast. Gulli, M.P., Jaquenoud, M., Shimada, Y., Niederhäuser, G., Wiget, P., Peter, M. Mol. Cell (2000) [Pubmed]
  27. Cdc24 regulates nuclear shuttling and recruitment of the Ste5 scaffold to a heterotrimeric G protein in Saccharomyces cerevisiae. Wang, Y., Chen, W., Simpson, D.M., Elion, E.A. J. Biol. Chem. (2005) [Pubmed]
  28. Site-specific regulation of the GEF Cdc24p by the scaffold protein Far1p during yeast mating. Wiget, P., Shimada, Y., Butty, A.C., Bi, E., Peter, M. EMBO J. (2004) [Pubmed]
  29. Oligomerization regulates the localization of Cdc24, the Cdc42 activator in Saccharomyces cerevisiae. Mionnet, C., Bogliolo, S., Arkowitz, R.A. J. Biol. Chem. (2008) [Pubmed]
  30. Genetic evidence for the roles of the bud-site-selection genes BUD5 and BUD2 in control of the Rsr1p (Bud1p) GTPase in yeast. Bender, A. Proc. Natl. Acad. Sci. U.S.A. (1993) [Pubmed]
  31. Control of the yeast bud-site assembly GTPase Cdc42. Catalysis of guanine nucleotide exchange by Cdc24 and stimulation of GTPase activity by Bem3. Zheng, Y., Cerione, R., Bender, A. J. Biol. Chem. (1994) [Pubmed]
  32. A Ser/Thr-rich multicopy suppressor of a cdc24 bud emergence defect. Bender, A., Pringle, J.R. Yeast (1992) [Pubmed]
  33. Residues of the Rho family GTPases Rho and Cdc42 that specify sensitivity to Dbl-like guanine nucleotide exchange factors. Li, R., Zheng, Y. J. Biol. Chem. (1997) [Pubmed]
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