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

• Published in: Cancer research (Chicago, Ill.) Vol. 65; no. 15; pp. 6685 - 6691
• Main Authors: TSUCHIHARA, Katsuya, LAPIN, Valentina, ROTTAPEL, Robert, RICHARDSON, Christopher D, BENCHIMOL, Samuel, TAK WAH MAK, BAKAL, Christopher, OKADA, Hitoshi, BROWN, Lauren, HIROTA-TSUCHIHARA, Masami, ZAUGG, Kathrin, HO, Alexandra, ITIE-YOUTEN, Annick, HARRIS-BRANDTS, Marees
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 01.08.2005
• Subjects: Aneuploidy; Animals; Apoptosis - genetics; Biological and medical sciences; Cell Cycle - genetics; Cell physiology; Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes; Centrosome - physiology; Chromosome aberrations; Cytoskeletal Proteins - genetics; Cytoskeletal Proteins - metabolism; Fundamental and applied biological sciences. Psychology; HCT116 Cells; Humans; Leukemia, Erythroblastic, Acute - genetics; Leukemia, Erythroblastic, Acute - pathology; Medical genetics; Medical sciences; Mice; Microtubules - metabolism; Molecular and cellular biology; NIH 3T3 Cells; Oligonucleotide Array Sequence Analysis; Promoter Regions, Genetic; Transcriptional Activation; Tumor Suppressor Protein p53 - genetics; Chromosomal aberration; Regulation(control); TP53 Gene; Cell death; Aneuploidy; Cytoskeleton associated protein 2; In vitro; Apoptosis; Tumor suppressor gene
• ISSN: 0008-5472; 1538-7445
• 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.