Ckap2 regulates aneuploidy, cell cycling, and cell death in a p53-dependent manner |
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Authors: | Tsuchihara Katsuya Lapin Valentina Bakal Christopher Okada Hitoshi Brown Lauren Hirota-Tsuchihara Masami Zaugg Kathrin Ho Alexandra Itie-Youten Annick Harris-Brandts Marees Rottapel Robert Richardson Christopher D Benchimol Samuel Mak Tak Wah |
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Affiliation: | The Campbell Family Institute for Breast Cancer Research, Ontario Cancer Institute, Ontario, Canada. |
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Abstract: | We used DNA microarray screening to identify Ckap2 (cytoskeleton associated protein 2) as a novel p53 target gene in a mouse erythroleukemia cell line. DNA damage induces human and mouse CKAP2 expression in a p53-dependent manner and p53 activates the Ckap2 promoter. Overexpressed Ckap2 colocalizes with and stabilizes microtubules. In p53-null cells, overexpression of Ckap2 induces tetraploidy with aberrant centrosome numbers, suggesting disturbed mitosis and cytokinesis. In p53-competent cells, Ckap2 does not induce tetraploidy but activates p53-mediated cell cycle arrest and apoptosis. Our data suggest the existence of a functional positive feedback loop in which Ckap2 activates the G1 tetraploidy checkpoint and prevents aneuploidy. |
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