Open AccessAlterations of anaphase-promoting complex genes in human colon cancer cells
Author(s) -
Qing Wang,
Caroline MoyretLalle,
Florence Couzon,
Christine Surbiguet-Clippe,
JeanChristophe Saurin,
Thierry Lorca,
Claudine Navarro,
Alain Puisieux
Publication year - 2003
Publication title -
oncogene
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.395
H-Index - 342
eISSN - 1476-5594
pISSN - 0950-9232
DOI - 10.1038/sj.onc.1206224
Subject(s) - anaphase promoting complex , biology , securin , microbiology and biotechnology , mitosis , cdc20 , cell cycle , cyclin b , ubiquitin ligase , spindle checkpoint , cyclin a2 , cell division control protein 4 , cyclin a , cyclin , f box protein , cyclin d , cyclin b1 , anaphase , ubiquitin , genetics , spindle apparatus , cyclin dependent kinase 1 , cell division , cancer , cell , gene
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.