Ckap2 regulates aneuploidy, cell cycling, and cell death in a p53-dependent manner.

نویسندگان

  • 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
چکیده

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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عنوان ژورنال:
  • Cancer research

دوره 65 15  شماره 

صفحات  -

تاریخ انتشار 2005