Alterations of anaphase-promoting complex genes in human colon cancer cells.
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.
Wang
Qing
Q
Centre d'Oncologie Génetique, INSERM U 453, Centre Léon Bérard, Lyon, France.
Moyret-Lalle
Caroline
C
Couzon
Florence
F
Surbiguet-Clippe
Christine
C
Saurin
Jean-Christophe
JC
Lorca
Thierry
T
Navarro
Claudine
C
Puisieux
Alain
A
D064173:Anaphase-Promoting Complex-Cyclosome; D000970:Antineoplastic Agents / Q000494:pharmacology; D064191:Apc3 Subunit, Anaphase-Promoting Complex-Cyclosome; D064194:Apc6 Subunit, Anaphase-Promoting Complex-Cyclosome; D064196:Apc8 Subunit, Anaphase-Promoting Complex-Cyclosome; D001943:Breast Neoplasms / Q000235:genetics; D006528:Carcinoma, Hepatocellular / Q000235:genetics; D002453:Cell Cycle / Q000235:genetics; D018797:Cell Cycle Proteins / Q000187:drug effects / Q000235:genetics; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000235:genetics*; D019926:Cyclin B / Q000235:genetics / Q000378:metabolism; D056744:Cyclin B1; D004847:Epithelial Cells / Q000473:pathology / Q000502:physiology; D005260:Female; D006801:Humans; D008025:Ligases / Q000235:genetics* / Q000378:metabolism; D008113:Liver Neoplasms / Q000235:genetics; D008545:Melanoma / Q000235:genetics; D008938:Mitosis; D009154:Mutation; D009447:Neuroblastoma / Q000235:genetics; D015739:Nocodazole / Q000494:pharmacology; D010051:Ovarian Neoplasms / Q000235:genetics; D016133:Polymerase Chain Reaction / Q000379:methods; D021122:Protein Subunits; D014407:Tumor Cells, Cultured; D043743:Ubiquitin-Protein Ligase Complexes
D000970:Antineoplastic Agents; D064191:Apc3 Subunit, Anaphase-Promoting Complex-Cyclosome; D064194:Apc6 Subunit, Anaphase-Promoting Complex-Cyclosome; D064196:Apc8 Subunit, Anaphase-Promoting Complex-Cyclosome; C534699:CCNB1 protein, human; C577395:CDC16 protein, human; C577440:CDC23 protein, human; C577366:CDC27 protein, human; D018797:Cell Cycle Proteins; D019926:Cyclin B; D056744:Cyclin B1; D021122:Protein Subunits; D043743:Ubiquitin-Protein Ligase Complexes; D064173:Anaphase-Promoting Complex-Cyclosome; D008025:Ligases; D015739:Nocodazole