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 (CDC23ΔTPR) 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.
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Acknowledgements
This work was supported by grants from the Comité Départemental du Rhône and the Comité Départemental de la Drôme de la Ligue de Lutte contre le Cancer, and from the Association pour la Recherche sur le Cancer.
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Wang, Q., Moyret-Lalle, C., Couzon, F. et al. Alterations of anaphase-promoting complex genes in human colon cancer cells. Oncogene 22, 1486–1490 (2003). https://doi.org/10.1038/sj.onc.1206224
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DOI: https://doi.org/10.1038/sj.onc.1206224
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