Data from Ckap2 Regulates Aneuploidy, Cell Cycling, and Cell Death in a p53-Dependent Manner

Katsuya Tsuchihara, Valentina Lapin,Christopher Bakal, Hitoshi Okada,Lauren Brown, Masami Hirota-Tsuchihara,Kathrin Zaugg, Alexandra Ho, Annick Itie-YouTen, Marees Harris-Brandts, Robert Rottapel, Christopher D. Richardson,Samuel Benchimol,Tak Wah Mak

crossref(2023)

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摘要
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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