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Gene Review

cut4  -  anaphase-promoting complex subunit Apc1

Schizosaccharomyces pombe 972h-

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Disease relevance of cut4


High impact information on cut4

  • The rapid degradation of Cut2 at anaphase requires its amino-terminal region and the activity of Cut9 (ref. 14), a component of the 20S cyclosome/anaphase-promoting complex (APC), which is necessary for cyclin destruction [2].
  • Loss of the anaphase-promoting complex in quiescent cells causes unscheduled hepatocyte proliferation [3].
  • The anaphase-promoting complex: it's not just for mitosis any more [4].
  • However, an abnormal spindle and/or unattached kinetochores activates a conserved spindle checkpoint that blocks APC function [5].
  • The results suggest that dual downregulation of CDK, one via the APC and the other via the CDK inhibitor, is a universal mechanism that is used to arrest cell cycle progression at G1 [6].

Biological context of cut4

  • At the restrictive temperature of 36 degrees C, lid1-6 mutant cells arrest with a "cut" phenotype similar to that of cut4 and cut9 mutants [7].
  • The 20S cyclosome complex (also known as the anaphase-promoting complex) has ubiquitin ligase activity and is required for mitotic cyclin destruction and sister chromatid separation [1].
  • Moreover, we demonstrate that cyclin-dependent kinase phosphorylation sites adjacent to the C-box may regulate the interaction with the APC [8].
  • The binding site for Pus1 was mapped to a cluster of repetitive sequences also found in the proteasome subunit SpRpn2 and the anaphase-promoting complex/cyclosome (APC/C) subunit Cut4 [9].
  • The spindle checkpoint coordinates cell cycle progression and chromosome segregation by inhibiting anaphase promoting complex/cyclosome until all kinetochores interact with the spindle properly [10].

Anatomical context of cut4

  • Genetic and biochemical experiments with several different organisms have documented that polo-like kinases are involved in many aspects of the cell cycle, such as activation of Cdc2, centrosome assembly and maturation, activation of the anaphase-promoting complex (APC) during the metaphase-anaphase transition, and cytokinesis [11].

Associations of cut4 with chemical compounds

  • DNA rereplication can also be induced in cells that enter mitosis prematurely because of lack of tyrosine phosphorylation of NIMX(cdc2) and impaired anaphase-promoting complex function [12].
  • Overexpression of Mad2p or inactivation of Slp1p, a regulator of the anaphase-promoting complex, also rescued the checkpoint defect of HU-treated rad3 cells [13].

Analytical, diagnostic and therapeutic context of cut4

  • In synchronized Arabidopsis cell cultures the cdc20 transcripts were present from early G2 until the M-phase exit, ccs52B from G2/M to M while ccs52A1 and ccs52A2 were from late M until early G2, suggesting consecutive action of these APC activators in the plant cell cycle [14].


  1. 20S cyclosome complex formation and proteolytic activity inhibited by the cAMP/PKA pathway. Yamashita, Y.M., Nakaseko, Y., Samejima, I., Kumada, K., Yamada, H., Michaelson, D., Yanagida, M. Nature (1996) [Pubmed]
  2. Cut2 proteolysis required for sister-chromatid seperation in fission yeast. Funabiki, H., Yamano, H., Kumada, K., Nagao, K., Hunt, T., Yanagida, M. Nature (1996) [Pubmed]
  3. Loss of the anaphase-promoting complex in quiescent cells causes unscheduled hepatocyte proliferation. Wirth, K.G., Ricci, R., Giménez-Abián, J.F., Taghybeeglu, S., Kudo, N.R., Jochum, W., Vasseur-Cognet, M., Nasmyth, K. Genes Dev. (2004) [Pubmed]
  4. The anaphase-promoting complex: it's not just for mitosis any more. Harper, J.W., Burton, J.L., Solomon, M.J. Genes Dev. (2002) [Pubmed]
  5. A Bub2p-dependent spindle checkpoint pathway regulates the Dbf2p kinase in budding yeast. Fesquet, D., Fitzpatrick, P.J., Johnson, A.L., Kramer, K.M., Toyn, J.H., Johnston, L.H. EMBO J. (1999) [Pubmed]
  6. Apc10 and Ste9/Srw1, two regulators of the APC-cyclosome, as well as the CDK inhibitor Rum1 are required for G1 cell-cycle arrest in fission yeast. Kominami, K., Seth-Smith, H., Toda, T. EMBO J. (1998) [Pubmed]
  7. The schizosaccharomyces pombe dim1(+) gene interacts with the anaphase-promoting complex or cyclosome (APC/C) component lid1(+) and is required for APC/C function. Berry, L.D., Feoktistova, A., Wright, M.D., Gould, K.L. Mol. Cell. Biol. (1999) [Pubmed]
  8. Two classes of the CDh1-type activators of the anaphase-promoting complex in plants: novel functional domains and distinct regulation. Tarayre, S., Vinardell, J.M., Cebolla, A., Kondorosi, A., Kondorosi, E. Plant Cell (2004) [Pubmed]
  9. Interaction of the anaphase-promoting complex/cyclosome and proteasome protein complexes with multiubiquitin chain-binding proteins. Seeger, M., Hartmann-Petersen, R., Wilkinson, C.R., Wallace, M., Samejima, I., Taylor, M.S., Gordon, C. J. Biol. Chem. (2003) [Pubmed]
  10. Spindle checkpoint signaling requires the mis6 kinetochore subcomplex, which interacts with mad2 and mitotic spindles. Saitoh, S., Ishii, K., Kobayashi, Y., Takahashi, K. Mol. Biol. Cell (2005) [Pubmed]
  11. Polo-like kinase 1 in the life and death of cancer cells. Liu, X., Erikson, R.L. Cell Cycle (2003) [Pubmed]
  12. Checkpoint defects leading to premature mitosis also cause endoreplication of DNA in Aspergillus nidulans. De Souza, C.P., Ye, X.S., Osmani, S.A. Mol. Biol. Cell (1999) [Pubmed]
  13. DNA replication checkpoint control mediated by the spindle checkpoint protein Mad2p in fission yeast. Sugimoto, I., Murakami, H., Tonami, Y., Moriyama, A., Nakanishi, M. J. Biol. Chem. (2004) [Pubmed]
  14. Arabidopsis anaphase-promoting complexes: multiple activators and wide range of substrates might keep APC perpetually busy. Fülöp, K., Tarayre, S., Kelemen, Z., Horváth, G., Kevei, Z., Nikovics, K., Bakó, L., Brown, S., Kondorosi, A., Kondorosi, E. Cell Cycle (2005) [Pubmed]
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