title: Ckap2 regulates aneuploidy, cell cycling, and cell death in a p53-dependent manner.
abstract: 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.
authors.affiliation: The Campbell Family Institute for Breast Cancer Research, Ontario Cancer Institute, Ontario, Canada.
authors.forename: Katsuya
authors.initials: K
authors.lastname: Tsuchihara
authors.forename: Valentina
authors.initials: V
authors.lastname: Lapin
authors.forename: Christopher
authors.initials: C
authors.lastname: Bakal
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Okada
authors.forename: Lauren
authors.initials: L
authors.lastname: Brown
authors.forename: Masami
authors.initials: M
authors.lastname: Hirota-Tsuchihara
authors.forename: Kathrin
authors.initials: K
authors.lastname: Zaugg
authors.forename: Alexandra
authors.initials: A
authors.lastname: Ho
authors.forename: Annick
authors.initials: A
authors.lastname: Itie-Youten
authors.forename: Marees
authors.initials: M
authors.lastname: Harris-Brandts
authors.forename: Robert
authors.initials: R
authors.lastname: Rottapel
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Richardson
authors.forename: Samuel
authors.initials: S
authors.lastname: Benchimol
authors.forename: Tak Wah
authors.initials: TW
authors.lastname: Mak
mesh_terms: 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*
chemical_list: C494575:CKAP2 protein, mouse; D003598:Cytoskeletal Proteins; D016159:Tumor Suppressor Protein p53