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

Cancer Res. 2005 Aug 1;65(15):6685-91. doi: 10.1158/0008-5472.CAN-04-4223.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aneuploidy*
  • Animals
  • Apoptosis / genetics
  • Cell Cycle / genetics
  • Centrosome / physiology
  • Cytoskeletal Proteins / genetics*
  • Cytoskeletal Proteins / metabolism
  • HCT116 Cells
  • Humans
  • Leukemia, Erythroblastic, Acute / genetics*
  • Leukemia, Erythroblastic, Acute / pathology
  • Mice
  • Microtubules / metabolism
  • NIH 3T3 Cells
  • Oligonucleotide Array Sequence Analysis
  • Promoter Regions, Genetic
  • Transcriptional Activation
  • Tumor Suppressor Protein p53 / genetics*


  • CKAP2 protein, mouse
  • Cytoskeletal Proteins
  • Tumor Suppressor Protein p53