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Gene Review

CDC20  -  cell division cycle 20

Homo sapiens

Synonyms: CDC20A, Cell division cycle protein 20 homolog, bA276H19.3, p55CDC
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Disease relevance of CDC20

  • In particular, CDC20 and MT2A represent a potential biomarker of human gastric cancer [1].
  • We observed overexpression of CDC20 in several oral squamous cell carcinoma (OSCC) cell lines and primary head and neck tumors and provide evidence that such overexpression of CDC20 is associated with premature anaphase promotion, resulting in mitotic abnormalities in OSCC cell lines [2].
  • HTLV-I Tax directly binds the Cdc20-associated anaphase-promoting complex and activates it ahead of schedule [3].
  • Overexpression of Cdc20 leads to impairment of the spindle assembly checkpoint and aneuploidization in oral cancer [2].
  • Identification of frequent impairment of the mitotic checkpoint and molecular analysis of the mitotic checkpoint genes, hsMAD2 and p55CDC, in human lung cancers [4].

High impact information on CDC20

  • Bub1 directly phosphorylates Cdc20 in vitro and inhibits the ubiquitin ligase activity of APC/C(Cdc20) catalytically [5].
  • Ectopic expression of the nonphosphorylatable Cdc20 mutant allows HeLa cells to escape from mitosis in the presence of spindle damage [5].
  • Mad1 and Cdc20 contain Mad2 binding motifs that share a common consensus [6].
  • Mad2 also undergoes a similar striking structural change upon binding to a Mad1 or Cdc20 binding motif peptide [6].
  • The tumour suppressor RASSF1A regulates mitosis by inhibiting the APC-Cdc20 complex [7].

Biological context of CDC20

  • Recent work has shown that activation of the APC in mitosis depends on CDC20, whereas APC is maintained active in G1 via association with the CDC20-related protein CDH1 [8].
  • The anaphase-promoting complex activated by CDC20 and CDH1 is a major ubiquitination system that controls the destruction of cell cycle regulators [9].
  • These mechanisms can explain the temporal order of APC activation by CDC20 and CDH1 and may help to ensure that exit from mitosis is not initiated before anaphase has occurred [10].
  • In contrast, the analysis of phosphorylated and nonphosphorylated forms of CDC20 suggests that CDC20 phosphorylation is neither sufficient nor required for APC activation [10].
  • BACKGROUND: Chromosome segregation and mitotic exit depend on activation of the anaphase-promoting complex (APC) by the substrate adaptor proteins CDC20 and CDH1 [11].

Anatomical context of CDC20


Associations of CDC20 with chemical compounds

  • Spindle checkpoint activation by nocodazole treatment enhances the association between p55CDC and His6-BUBR1 [13].
  • Mutation of a conserved lysine in this region weakened Cdc20 binding and correspondingly reduced checkpoint function [16].
  • Based on this evidence, and by means of specific cell cycle modulators, such as nocodazole and hydroxyurea, we demonstrated that both TSA and NaBt were responsible for loss of p55CDC/Cdc20 expression, but with different mechanisms of action [17].
  • Further, we have identified a unique polyhistidine motif with metal binding property adjacent to this second binding domain that may be important for maintaining the overall conformation of Cdc20 for its binding to Mad2 [18].
  • We identified speriolin and determined that it is a novel spermatogenic cell-specific Cdc20-binding protein, is present in the cytoplasm, and is concentrated at the centrosomes of spermatocytes and spermatids and that a leucine zipper domain is required to target speriolin to the centrosome [19].

Physical interactions of CDC20

  • Mad2 is a component of the SAC effector complex that sequesters Cdc20 to halt anaphase [20].
  • Conversely depletion of RABP1 by RNA interference prevented both the localization of RASSF1A to the spindle poles as well as its binding to Cdc20, resulting in premature destruction of mitotic cyclins and acceleration of mitotic progression [21].
  • The spindle checkpoint protein Mad2 inhibits the activity of APC/C through direct binding to its activator Cdc20 [22].

Enzymatic interactions of CDC20

  • Upon checkpoint activation, Bub1 itself is hyperphosphorylated and its kinase activity toward Cdc20 is stimulated [5].

Regulatory relationships of CDC20


Other interactions of CDC20

  • Mitotic regulation of the APC activator proteins CDC20 and CDH1 [10].
  • Most importantly, we show that Nek2A binds directly to the APC/C, also in an MR-dependent manner, even in the absence of the adaptor protein Cdc20 [24].
  • In tax-expressing cells, the Cdc20-associated anaphase promoting complex (APC(Cdc20)), an E3 ubiquitin ligase that controls metaphase to anaphase transition, becomes active before cellular entry into mitosis as evidenced by premature cyclin B1 polyubiquitination and degradation during S/G(2) [3].
  • Consistent with the notion that Tax activates APC(Cdc20) directly, Tax is found to coimmunoprecipitate with Cdc20 and Cdc27/APC3 [3].
  • APC activation by CDH1 depends on a conserved C-terminal motif that is also found in CDC20 and APC10 [11].

Analytical, diagnostic and therapeutic context of CDC20


  1. Identification of gastric cancer-related genes using a cDNA microarray containing novel expressed sequence tags expressed in gastric cancer cells. Kim, J.M., Sohn, H.Y., Yoon, S.Y., Oh, J.H., Yang, J.O., Kim, J.H., Song, K.S., Rho, S.M., Yoo, H.S., Yoo, H.S., Kim, Y.S., Kim, J.G., Kim, N.S. Clin. Cancer Res. (2005) [Pubmed]
  2. Overexpression of Cdc20 leads to impairment of the spindle assembly checkpoint and aneuploidization in oral cancer. Mondal, G., Sengupta, S., Panda, C.K., Gollin, S.M., Saunders, W.S., Roychoudhury, S. Carcinogenesis (2007) [Pubmed]
  3. HTLV-I Tax directly binds the Cdc20-associated anaphase-promoting complex and activates it ahead of schedule. Liu, B., Hong, S., Tang, Z., Yu, H., Giam, C.Z. Proc. Natl. Acad. Sci. U.S.A. (2005) [Pubmed]
  4. Identification of frequent impairment of the mitotic checkpoint and molecular analysis of the mitotic checkpoint genes, hsMAD2 and p55CDC, in human lung cancers. Takahashi, T., Haruki, N., Nomoto, S., Masuda, A., Saji, S., Osada, H., Takahashi, T. Oncogene (1999) [Pubmed]
  5. Phosphorylation of Cdc20 by Bub1 provides a catalytic mechanism for APC/C inhibition by the spindle checkpoint. Tang, Z., Shu, H., Oncel, D., Chen, S., Yu, H. Mol. Cell (2004) [Pubmed]
  6. The Mad2 spindle checkpoint protein undergoes similar major conformational changes upon binding to either Mad1 or Cdc20. Luo, X., Tang, Z., Rizo, J., Yu, H. Mol. Cell (2002) [Pubmed]
  7. The tumour suppressor RASSF1A regulates mitosis by inhibiting the APC-Cdc20 complex. Song, M.S., Song, S.J., Ayad, N.G., Chang, J.S., Lee, J.H., Hong, H.K., Lee, H., Choi, N., Kim, J., Kim, H., Kim, J.W., Choi, E.J., Kirschner, M.W., Lim, D.S. Nat. Cell Biol. (2004) [Pubmed]
  8. Expression of the CDH1-associated form of the anaphase-promoting complex in postmitotic neurons. Gieffers, C., Peters, B.H., Kramer, E.R., Dotti, C.G., Peters, J.M. Proc. Natl. Acad. Sci. U.S.A. (1999) [Pubmed]
  9. Nuclear localization of the cell cycle regulator CDH1 and its regulation by phosphorylation. Zhou, Y., Ching, Y.P., Chun, A.C., Jin, D.Y. J. Biol. Chem. (2003) [Pubmed]
  10. Mitotic regulation of the APC activator proteins CDC20 and CDH1. Kramer, E.R., Scheuringer, N., Podtelejnikov, A.V., Mann, M., Peters, J.M. Mol. Biol. Cell (2000) [Pubmed]
  11. TPR subunits of the anaphase-promoting complex mediate binding to the activator protein CDH1. Vodermaier, H.C., Gieffers, C., Maurer-Stroh, S., Eisenhaber, F., Peters, J.M. Curr. Biol. (2003) [Pubmed]
  12. Mammalian p55CDC mediates association of the spindle checkpoint protein Mad2 with the cyclosome/anaphase-promoting complex, and is involved in regulating anaphase onset and late mitotic events. Kallio, M., Weinstein, J., Daum, J.R., Burke, D.J., Gorbsky, G.J. J. Cell Biol. (1998) [Pubmed]
  13. p55CDC/hCDC20 is associated with BUBR1 and may be a downstream target of the spindle checkpoint kinase. Wu, H., Lan, Z., Li, W., Wu, S., Weinstein, J., Sakamoto, K.M., Dai, W. Oncogene (2000) [Pubmed]
  14. The anaphase promoting complex/cyclosome is recruited to centromeres by the spindle assembly checkpoint. Acquaviva, C., Herzog, F., Kraft, C., Pines, J. Nat. Cell Biol. (2004) [Pubmed]
  15. A novel mammalian protein, p55CDC, present in dividing cells is associated with protein kinase activity and has homology to the Saccharomyces cerevisiae cell division cycle proteins Cdc20 and Cdc4. Weinstein, J., Jacobsen, F.W., Hsu-Chen, J., Wu, T., Baum, L.G. Mol. Cell. Biol. (1994) [Pubmed]
  16. Spindle checkpoint function requires Mad2-dependent Cdc20 binding to the Mad3 homology domain of BubR1. Davenport, J., Harris, L.D., Goorha, R. Exp. Cell Res. (2006) [Pubmed]
  17. Effects of histone deacetylase inhibitors on p55CDC/Cdc20 expression in HT29 cell line. Iacomino, G., Medici, M.C., Napoli, D., Russo, G.L. J. Cell. Biochem. (2006) [Pubmed]
  18. A new Mad2-interacting domain of Cdc20 is critical for the function of Mad2-Cdc20 complex in the spindle assembly checkpoint. Mondal, G., Baral, R.N., Roychoudhury, S. Biochem. J. (2006) [Pubmed]
  19. Speriolin is a novel spermatogenic cell-specific centrosomal protein associated with the seventh WD motif of Cdc20. Goto, M., Eddy, E.M. J. Biol. Chem. (2004) [Pubmed]
  20. The Mad1/Mad2 complex as a template for Mad2 activation in the spindle assembly checkpoint. De Antoni, A., Pearson, C.G., Cimini, D., Canman, J.C., Sala, V., Nezi, L., Mapelli, M., Sironi, L., Faretta, M., Salmon, E.D., Musacchio, A. Curr. Biol. (2005) [Pubmed]
  21. The centrosomal protein RAS association domain family protein 1A (RASSF1A)-binding protein 1 regulates mitotic progression by recruiting RASSF1A to spindle poles. Song, M.S., Chang, J.S., Song, S.J., Yang, T.H., Lee, H., Lim, D.S. J. Biol. Chem. (2005) [Pubmed]
  22. Purification and assay of Mad2: a two-state inhibitor of anaphase-promoting complex/cyclosome. Luo, X., Yu, H. Meth. Enzymol. (2005) [Pubmed]
  23. Polo-like kinase-1 is required for bipolar spindle formation but is dispensable for anaphase promoting complex/Cdc20 activation and initiation of cytokinesis. van Vugt, M.A., van de Weerdt, B.C., Vader, G., Janssen, H., Calafat, J., Klompmaker, R., Wolthuis, R.M., Medema, R.H. J. Biol. Chem. (2004) [Pubmed]
  24. Early mitotic degradation of Nek2A depends on Cdc20-independent interaction with the APC/C. Hayes, M.J., Kimata, Y., Wattam, S.L., Lindon, C., Mao, G., Yamano, H., Fry, A.M. Nat. Cell Biol. (2006) [Pubmed]
  25. WD repeat-containing mitotic checkpoint proteins act as transcriptional repressors during interphase. Yoon, Y.M., Baek, K.H., Jeong, S.J., Shin, H.J., Ha, G.H., Jeon, A.H., Hwang, S.G., Chun, J.S., Lee, C.W. FEBS Lett. (2004) [Pubmed]
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