Ckap2 regulates aneuploidy, cell cycling, and cell death in a p53-dependent manner.
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.
Tsuchihara
Katsuya
K
The Campbell Family Institute for Breast Cancer Research, Ontario Cancer Institute, Ontario, Canada.
Lapin
Valentina
V
Bakal
Christopher
C
Okada
Hitoshi
H
Brown
Lauren
L
Hirota-Tsuchihara
Masami
M
Zaugg
Kathrin
K
Ho
Alexandra
A
Itie-Youten
Annick
A
Harris-Brandts
Marees
M
Rottapel
Robert
R
Richardson
Christopher D
CD
Benchimol
Samuel
S
Mak
Tak Wah
TW
D000782:Aneuploidy; D000818:Animals; D017209:Apoptosis / Q000235:genetics; D002453:Cell Cycle / Q000235:genetics; D018385:Centrosome / Q000502:physiology; D003598:Cytoskeletal Proteins / Q000235:genetics* / Q000378:metabolism; D045325:HCT116 Cells; D006801:Humans; D004915:Leukemia, Erythroblastic, Acute / Q000235:genetics* / Q000473:pathology; D051379:Mice; D008870:Microtubules / Q000378:metabolism; D041681:NIH 3T3 Cells; D020411:Oligonucleotide Array Sequence Analysis; D011401:Promoter Regions, Genetic; D015533:Transcriptional Activation; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
C494575:CKAP2 protein, mouse; D003598:Cytoskeletal Proteins; D016159:Tumor Suppressor Protein p53