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Gene Review

cdc2  -  CG5363 gene product from transcript CG5363-RA

Drosophila melanogaster

Synonyms: 5363, CDC2, CDCDm, CDK1, CDK1/CDC2, ...
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High impact information on cdc2

  • In mammalian cells, LATS1 is phosphorylated in a cell-cycle-dependent manner and complexes with CDC2 in early mitosis [1].
  • We propose that cyclin A-cdc2 kinase at the G2 to M transition of meiosis I activates a target necessary for meiosis II, thereby coupling the two meiotic divisions [2].
  • Mutations in E(sev)3B also dominantly enhance mutations in Dmcdc2, the gene encoding the p34 protein kinase that regulates the G2/M transition [3].
  • Finally, the phenotypes observed suggest that the cdc 10/ankyrin repeat region within the intracellular domain plays an essential role in the postulated signal transduction events [4].
  • Genetic and biochemical studies have indicated that the cdc25 protein controls the entry into mitosis by triggering tyrosine dephosphorylation of the cdc2 protein kinase [5].

Biological context of cdc2

  • Here we show that neural progenitor asymmetric divisions require the cell-cycle regulator cdc2 [6].
  • The gene that encodes the Drosophila cdc2 homologue maps to a single locus in the Drosophila genome at 31E on chromosome 2 [7].
  • This library was introduced into S.pombe cdc2 and cdc25 mutants, and plasmids isolated carrying cDNAs that complement these mutations [7].
  • Deletion of these sequences is correlated with loss of Gro/TLE phosphorylation by cdc2 in vitro and okadaic acid-induced Gro/TLE hyperphosphorylation in vivo [8].
  • Deficiencies that removed one of the Drosophila cdc2 genes and the cyclin A gene had no effect on replication during embryogenesis [9].

Anatomical context of cdc2


Associations of cdc2 with chemical compounds


Physical interactions of cdc2

  • Cdc2 binds to E2F in vitro, and post-transcriptionally promotes its accumulation in vivo [18].
  • During cell cycles 2-7, Cdc2/Cyclin complexes are continuously present and show little fluctuation in abundance, phosphomodification, or activity [19].

Enzymatic interactions of cdc2


Regulatory relationships of cdc2


Other interactions of cdc2

  • Surprisingly, Rux had a stimulating effect on CycA-Cdk1 activity when present in low concentrations [25].
  • Since it has been shown that active cdc2 is required to maintain the arrest seen in fzy embryos we wished to determine if pim+ and thr+ were also required [26].
  • Cdk1 inhibition by Rux did not rely on inhibitory phosphorylation, disruption of cyclin-Cdk complex formation or changes in subcellular localization [25].
  • Our findings link cdc2 with asymmetric divisions, and explain why the asymmetric localization of molecules like Inscuteable show cell-cycle dependence [6].
  • The corresponding sites in the closely related Cdk1 (Thr 14 and Tyr 15) are of crucial importance for regulation of the G2/M transition by myt1 and wee1 kinases and cdc25 phosphatases [27].

Analytical, diagnostic and therapeutic context of cdc2


  1. Human homologue of the Drosophila melanogaster lats tumour suppressor modulates CDC2 activity. Tao, W., Zhang, S., Turenchalk, G.S., Stewart, R.A., St John, M.A., Chen, W., Xu, T. Nat. Genet. (1999) [Pubmed]
  2. roughex is a dose-dependent regulator of the second meiotic division during Drosophila spermatogenesis. Gönczy, P., Thomas, B.J., DiNardo, S. Cell (1994) [Pubmed]
  3. Mutations in Hsp83 and cdc37 impair signaling by the sevenless receptor tyrosine kinase in Drosophila. Cutforth, T., Rubin, G.M. Cell (1994) [Pubmed]
  4. Specific truncations of Drosophila Notch define dominant activated and dominant negative forms of the receptor. Rebay, I., Fehon, R.G., Artavanis-Tsakonas, S. Cell (1993) [Pubmed]
  5. The cdc25 protein contains an intrinsic phosphatase activity. Dunphy, W.G., Kumagai, A. Cell (1991) [Pubmed]
  6. cdc2 links the Drosophila cell cycle and asymmetric division machineries. Tio, M., Udolph, G., Yang, X., Chia, W. Nature (2001) [Pubmed]
  7. Complementation of fission yeast cdc2ts and cdc25ts mutants identifies two cell cycle genes from Drosophila: a cdc2 homologue and string. Jimenez, J., Alphey, L., Nurse, P., Glover, D.M. EMBO J. (1990) [Pubmed]
  8. A role for cell cycle-regulated phosphorylation in Groucho-mediated transcriptional repression. Nuthall, H.N., Joachim, K., Palaparti, A., Stifani, S. J. Biol. Chem. (2002) [Pubmed]
  9. Identification of genomic regions required for DNA replication during Drosophila embryogenesis. Smith, A.V., King, J.A., Orr-Weaver, T.L. Genetics (1993) [Pubmed]
  10. A genetic screen for suppressors and enhancers of the Drosophila cdk1-cyclin B identifies maternal factors that regulate microtubule and microfilament stability. Ji, J.Y., Haghnia, M., Trusty, C., Goldstein, L.S., Schubiger, G. Genetics (2002) [Pubmed]
  11. The division of Drosophila germline stem cells and their precursors requires a specific cyclin. Wang, Z., Lin, H. Curr. Biol. (2005) [Pubmed]
  12. Functional analysis of the Drosophila CDC2 Dm gene in fission yeast. Bejarano, E.R., Muñoz, M.J., Jimenez, J. Mol. Gen. Genet. (1995) [Pubmed]
  13. Exit from mitosis in Drosophila syncytial embryos requires proteolysis and cyclin degradation, and is associated with localized dephosphorylation. Su, T.T., Sprenger, F., DiGregorio, P.J., Campbell, S.D., O'Farrell, P.H. Genes Dev. (1998) [Pubmed]
  14. The cdc25 protein controls tyrosine dephosphorylation of the cdc2 protein in a cell-free system. Kumagai, A., Dunphy, W.G. Cell (1991) [Pubmed]
  15. Hamartin and tuberin interaction with the G2/M cyclin-dependent kinase CDK1 and its regulatory cyclins A and B. Catania, M.G., Mischel, P.S., Vinters, H.V. J. Neuropathol. Exp. Neurol. (2001) [Pubmed]
  16. Pendulin, a Drosophila protein with cell cycle-dependent nuclear localization, is required for normal cell proliferation. Küssel, P., Frasch, M. J. Cell Biol. (1995) [Pubmed]
  17. Localization and posttranslational modifications of otefin, a protein required for vesicle attachment to chromatin, during Drosophila melanogaster development. Ashery-Padan, R., Ulitzur, N., Arbel, A., Goldberg, M., Weiss, A.M., Maus, N., Fisher, P.A., Gruenbaum, Y. Mol. Cell. Biol. (1997) [Pubmed]
  18. Kinase-independent activity of Cdc2/cyclin A prevents the S phase in the Drosophila cell cycle. Hayashi, S., Yamaguchi, M. Genes Cells (1999) [Pubmed]
  19. Distinct molecular mechanism regulate cell cycle timing at successive stages of Drosophila embryogenesis. Edgar, B.A., Sprenger, F., Duronio, R.J., Leopold, P., O'Farrell, P.H. Genes Dev. (1994) [Pubmed]
  20. Ectopic expression of the Drosophila Cdk1 inhibitory kinases, Wee1 and Myt1, interferes with the second mitotic wave and disrupts pattern formation during eye development. Price, D.M., Jin, Z., Rabinovitch, S., Campbell, S.D. Genetics (2002) [Pubmed]
  21. The Drosophila ATM homologue Mei-41 has an essential checkpoint function at the midblastula transition. Sibon, O.C., Laurençon, A., Hawley, R., Theurkauf, W.E. Curr. Biol. (1999) [Pubmed]
  22. Drosophila Wee1 kinase regulates Cdk1 and mitotic entry during embryogenesis. Stumpff, J., Duncan, T., Homola, E., Campbell, S.D., Su, T.T. Curr. Biol. (2004) [Pubmed]
  23. Activating the DNA damage checkpoint in a developmental context. Su, T.T., Walker, J., Stumpff, J. Curr. Biol. (2000) [Pubmed]
  24. Dmcdc2 kinase is required for both meiotic divisions during Drosophila spermatogenesis and is activated by the Twine/cdc25 phosphatase. Sigrist, S., Ried, G., Lehner, C.F. Mech. Dev. (1995) [Pubmed]
  25. Rux is a cyclin-dependent kinase inhibitor (CKI) specific for mitotic cyclin-Cdk complexes. Foley, E., O'Farrell, P.H., Sprenger, F. Curr. Biol. (1999) [Pubmed]
  26. Mutations affecting chromatid separation in Drosophila: the fizzy metaphase arrest persists in pimples fizzy and fizzy three rows double mutants. Philp, A.V., Glover, D.M. Exp. Cell Res. (1997) [Pubmed]
  27. A screen for modifiers of cyclin E function in Drosophila melanogaster identifies Cdk2 mutations, revealing the insignificance of putative phosphorylation sites in Cdk2. Lane, M.E., Elend, M., Heidmann, D., Herr, A., Marzodko, S., Herzig, A., Lehner, C.F. Genetics (2000) [Pubmed]
  28. Drosophila cdc2 homologs: a functional homolog is coexpressed with a cognate variant. Lehner, C.F., O'Farrell, P.H. EMBO J. (1990) [Pubmed]
  29. The L63 gene is necessary for the ecdysone-induced 63E late puff and encodes CDK proteins required for Drosophila development. Stowers, R.S., Garza, D., Rascle, A., Hogness, D.S. Dev. Biol. (2000) [Pubmed]
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