Ckap2 Regulates Aneuploidy, Cell Cycling, and Cell Death in a p53-Dependent Manner
| Autor: | Annick Itie-Youten, Marees Harris-Brandts, Valentina Lapin, Katsuya Tsuchihara, Masami Hirota-Tsuchihara, Kathrin Zaugg, Lauren E. Brown, Tak W. Mak, Samuel Benchimol, Alexandra Ho, Hitoshi Okada, Chris Bakal, Robert Rottapel, Christopher D. Richardson |
|---|---|
| Rok vydání: | 2005 |
| Předmět: |
Transcriptional Activation
Cancer Research Programmed cell death Cell cycle checkpoint DNA damage Cell Apoptosis Biology Microtubules Mice medicine Animals Humans Promoter Regions Genetic Cytoskeleton Mitosis Oligonucleotide Array Sequence Analysis Centrosome Cell Cycle Aneuploidy HCT116 Cells Cell biology Cytoskeletal Proteins medicine.anatomical_structure Oncology NIH 3T3 Cells Cancer research Leukemia Erythroblastic Acute Tumor Suppressor Protein p53 Cytokinesis |
| Zdroj: | Cancer Research. 65:6685-6691 |
| ISSN: | 1538-7445 0008-5472 |
| DOI: | 10.1158/0008-5472.can-04-4223 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|