Autor: |
Tak Wah Mak, Samuel Benchimol, Christopher D. Richardson, Robert Rottapel, Marees Harris-Brandts, Annick Itie-YouTen, Alexandra Ho, Kathrin Zaugg, Masami Hirota-Tsuchihara, Lauren Brown, Hitoshi Okada, Christopher Bakal, Valentina Lapin, Katsuya Tsuchihara |
Rok vydání: |
2023 |
DOI: |
10.1158/0008-5472.c.6493653.v1 |
Popis: |
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. |
Databáze: |
OpenAIRE |
Externí odkaz: |
|