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Gene Review

CDC4  -  SCF ubiquitin ligase complex subunit CDC4

Saccharomyces cerevisiae S288c

Synonyms: Cell division control protein 4, E3 ubiquitin ligase complex SCF subunit CDC4, F-box protein CDC4, YFL009W
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Disease relevance of CDC4


High impact information on CDC4


Biological context of CDC4

  • We have isolated three mutant alleles of CDC4 (cdc4-10, cdc4-11, and cdc4-16) which suppress the nuclear division defect of cdc20-1 cells [6].
  • The idea that RAD24 overexpression induces DNA damage, perhaps by interfering with replication/repair complexes, is further supported by our observation that RAD24 overexpression increases mitotic chromosome recombination in CDC4 strains [7].
  • Cdc4, a protein required for the onset of S phase, serves an essential function during G(2)/M transition in Saccharomyces cerevisiae [6].
  • Collectively, these observations suggest that, in addition to its involvement in the initiation of S phase, Cdc4 may also be required for the onset of anaphase [6].
  • We report here significant primary sequence homology among the predicted translational products of three genes: CDC4 , CDC36 and ets [1].

Anatomical context of CDC4

  • Using antisera, directed against a TrpE-CDC4 fusion protein, to analyze immuno-blots of different subcellular fractions from yeast, we demonstrated that the CDC4 gene product localizes in the nucleus by two different biochemical preparations of the yeast nucleoskeletal proteins [8].
  • Evolutionary conservation of the Sud1/CDC4 pathway suggests that phosphorylation-coupled proteolysis may be a general feature of nearly all eukaryotic cell cycles [9].

Associations of CDC4 with chemical compounds


Physical interactions of CDC4

  • An essential domain within Cdc34p is required for binding to a complex containing Cdc4p and Cdc53p in Saccharomyces cerevisiae [11].
  • Cic1 interacts in vitro and in vivo with Cdc4, suggesting a function as a new kind of substrate recruiting factor or adaptor associated with the proteasome [12].

Enzymatic interactions of CDC4

  • SIC1 is ubiquitinated in vitro by a pathway that requires CDC4, CDC34, and cyclin/CDK activities [13].
  • Indeed, we have found that Cdc6 is ubiquitinated in vivo and degraded by a Cdc4-dependent mechanism [14].

Regulatory relationships of CDC4


Other interactions of CDC4

  • To identify additional factors necessary for the inhibition of the Cdk1/Cdc28 kinase in G1, we isolated mutants that can replicate DNA in the absence of Cdc4 function [16].
  • Here we demonstrate that Cdc4p, Cdc34p, and Cdc53p interact in vivo [11].
  • Ubiquitin chain formation is abrogated in cdc4ts mutant extracts and assembly restored by the addition of exogenous CDC4, suggesting a direct role for this protein in SIC1 multiubiquitination [13].
  • This possibility is supported by the finding that CDC4 has no upstream SCB or MCB elements, whereas SCM4 and HFS1 have either an exact or close match to the SCB [17].
  • Saccharomyces cerevisiae proteins Cdc4 and Cdc20 contain WD40 repeats and participate in proteolytic processes [6].

Analytical, diagnostic and therapeutic context of CDC4

  • All three proteins migrate in gel filtration to sizes that greatly exceed their actual size suggesting that they form stable associations with other proteins and we observe Cdc4p, Cdc34p, and Cdc53p fractionating into overlapping families of high molecular weight complexes [11].


  1. A relationship between the yeast cell cycle genes CDC4 and CDC36 and the ets sequence of oncogenic virus E26. Peterson, T.A., Yochem, J., Byers, B., Nunn, M.F., Duesberg, P.H., Doolittle, R.F., Reed, S.I. Nature (1984) [Pubmed]
  2. Fus3-regulated Tec1 degradation through SCFCdc4 determines MAPK signaling specificity during mating in yeast. Chou, S., Huang, L., Liu, H. Cell (2004) [Pubmed]
  3. A deduced gene product from the Drosophila neurogenic locus, enhancer of split, shows homology to mammalian G-protein beta subunit. Hartley, D.A., Preiss, A., Artavanis-Tsakonas, S. Cell (1988) [Pubmed]
  4. Genes that act before conjugation to prepare the Saccharomyces cerevisiae nucleus for caryogamy. Dutcher, S.K., Hartwell, L.H. Cell (1983) [Pubmed]
  5. Multisite phosphorylation of a CDK inhibitor sets a threshold for the onset of DNA replication. Nash, P., Tang, X., Orlicky, S., Chen, Q., Gertler, F.B., Mendenhall, M.D., Sicheri, F., Pawson, T., Tyers, M. Nature (2001) [Pubmed]
  6. Cdc4, a protein required for the onset of S phase, serves an essential function during G(2)/M transition in Saccharomyces cerevisiae. Goh, P.Y., Surana, U. Mol. Cell. Biol. (1999) [Pubmed]
  7. G2/M checkpoint genes of Saccharomyces cerevisiae: further evidence for roles in DNA replication and/or repair. Lydall, D., Weinert, T. Mol. Gen. Genet. (1997) [Pubmed]
  8. The CDC4 gene product is associated with the yeast nuclear skeleton. Choi, W.J., Clark, M.W., Chen, J.X., Jong, A.Y. Biochem. Biophys. Res. Commun. (1990) [Pubmed]
  9. sud1(+) targets cyclin-dependent kinase-phosphorylated Cdc18 and Rum1 proteins for degradation and stops unwanted diploidization in fission yeast. Jallepalli, P.V., Tien, D., Kelly, T.J. Proc. Natl. Acad. Sci. U.S.A. (1998) [Pubmed]
  10. DNA ethylations induced by ethylnitrosourea in the wild type, cdc4 and cdc7 strains of Saccharomyces cerevisiae. Fox, J.C., Edwards, S., Waters, R. Mutagenesis (1986) [Pubmed]
  11. An essential domain within Cdc34p is required for binding to a complex containing Cdc4p and Cdc53p in Saccharomyces cerevisiae. Mathias, N., Steussy, C.N., Goebl, M.G. J. Biol. Chem. (1998) [Pubmed]
  12. Cic1, an adaptor protein specifically linking the 26S proteasome to its substrate, the SCF component Cdc4. Jäger, S., Strayle, J., Heinemeyer, W., Wolf, D.H. EMBO J. (2001) [Pubmed]
  13. SIC1 is ubiquitinated in vitro by a pathway that requires CDC4, CDC34, and cyclin/CDK activities. Verma, R., Feldman, R.M., Deshaies, R.J. Mol. Biol. Cell (1997) [Pubmed]
  14. The Cdc6 protein is ubiquitinated in vivo for proteolysis in Saccharomyces cerevisiae. Sánchez, M., Calzada, A., Bueno, A. J. Biol. Chem. (1999) [Pubmed]
  15. SCM4, a gene that suppresses mutant cdc4 function in budding yeast. Smith, S.A., Kumar, P., Johnston, I., Rosamond, J. Mol. Gen. Genet. (1992) [Pubmed]
  16. The transcription factor Swi5 regulates expression of the cyclin kinase inhibitor p40SIC1. Knapp, D., Bhoite, L., Stillman, D.J., Nasmyth, K. Mol. Cell. Biol. (1996) [Pubmed]
  17. Starting to cycle: G1 controls regulating cell division in budding yeast. Sherlock, G., Rosamond, J. J. Gen. Microbiol. (1993) [Pubmed]
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