Alterations of anaphase-promoting complex genes in human colon cancer cells

Oncogene. 2003 Mar 13;22(10):1486-90. doi: 10.1038/sj.onc.1206224.

Abstract

Ubiquitin-mediated proteolysis of cell cycle regulators is a major element of the cell cycle control. The anaphase-promoting complex (APC/C) is a large multisubunit ubiquitin-protein ligase required for the ubiquitination and degradation of G1 and mitotic checkpoint regulators. APC/C-dependent proteolysis regulates cyclin levels in G1, and triggers the separation of sister chromatids at the metaphase-anaphase transition and the destruction of mitotic cyclins at the end of mitosis. Furthermore, it was recently shown that APC/C regulates the degradation of crucial regulators of signal transduction pathways. We report here gene alterations in several components of this complex in human colon cancer cells, including APC6/CDC16 and APC8/CDC23 which are known to be key function elements. The experimental expression of a truncation mutant of APC8/CDC23 subunit (CDC23DeltaTPR) leads to abnormal levels of APC/C targets such as cyclin B1 and disturbs the cell cycle progression of colon epithelial cells through mitosis. Overall, these data support the hypothesis of a deleterious role of these mutations during colorectal carcinogenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anaphase-Promoting Complex-Cyclosome
  • Antineoplastic Agents / pharmacology
  • Apc3 Subunit, Anaphase-Promoting Complex-Cyclosome
  • Apc6 Subunit, Anaphase-Promoting Complex-Cyclosome
  • Apc8 Subunit, Anaphase-Promoting Complex-Cyclosome
  • Breast Neoplasms / genetics
  • Carcinoma, Hepatocellular / genetics
  • Cell Cycle / genetics
  • Cell Cycle Proteins / drug effects
  • Cell Cycle Proteins / genetics
  • Colonic Neoplasms / drug therapy
  • Colonic Neoplasms / genetics*
  • Cyclin B / genetics
  • Cyclin B / metabolism
  • Cyclin B1
  • Epithelial Cells / pathology
  • Epithelial Cells / physiology
  • Female
  • Humans
  • Ligases / genetics*
  • Ligases / metabolism
  • Liver Neoplasms / genetics
  • Melanoma / genetics
  • Mitosis
  • Mutation
  • Neuroblastoma / genetics
  • Nocodazole / pharmacology
  • Ovarian Neoplasms / genetics
  • Polymerase Chain Reaction / methods
  • Protein Subunits
  • Tumor Cells, Cultured
  • Ubiquitin-Protein Ligase Complexes*

Substances

  • Antineoplastic Agents
  • Apc3 Subunit, Anaphase-Promoting Complex-Cyclosome
  • Apc6 Subunit, Anaphase-Promoting Complex-Cyclosome
  • Apc8 Subunit, Anaphase-Promoting Complex-Cyclosome
  • CCNB1 protein, human
  • CDC16 protein, human
  • CDC23 protein, human
  • CDC27 protein, human
  • Cell Cycle Proteins
  • Cyclin B
  • Cyclin B1
  • Protein Subunits
  • Ubiquitin-Protein Ligase Complexes
  • Anaphase-Promoting Complex-Cyclosome
  • Ligases
  • Nocodazole