TTK/hMps1 Participates in the Regulation of DNA Damage Checkpoint Response by Phosphorylating CHK2 on Threonine 68
| Autor: | Yen-Hsiu Yeh, Yi Hung Ou, Shiaw-Wei Tyan, Yi-Fan Chou, Jen Hsuan Wei, Chen-Yang Shen, Te-Ping Sun, Sheau-Yann Shieh |
|---|---|
| Rok vydání: | 2005 |
| Předmět: |
Threonine
Cell cycle checkpoint Cell Cycle Proteins environment and public health Biochemistry Radiation Ionizing Phosphorylation RNA Small Interfering Glutathione Transferase biology Cell Cycle Protein-Tyrosine Kinases Cell biology Spindle checkpoint biological phenomena cell phenomena and immunity Cell Division Plasmids Protein Binding Signal Transduction G2 Phase animal structures Ultraviolet Rays DNA damage Cdc25 Recombinant Fusion Proteins Blotting Western Cyclin B Protein Serine-Threonine Kinases Transfection Models Biological Cell Line Cell Line Tumor Two-Hybrid System Techniques Escherichia coli Humans Immunoprecipitation CHEK1 Cyclin B1 Molecular Biology Cyclin-dependent kinase 1 Cell Biology G2-M DNA damage checkpoint Molecular biology Checkpoint Kinase 2 enzymes and coenzymes (carbohydrates) Mutation biology.protein Tyrosine Tumor Suppressor Protein p53 Protein Kinases DNA Damage HeLa Cells |
| Zdroj: | Journal of Biological Chemistry. 280:7748-7757 |
| ISSN: | 0021-9258 |
| Popis: | CHK2/hCds1 plays important roles in the DNA damage-induced cell cycle checkpoint by phosphorylating several important targets, such as Cdc25 and p53. To obtain a better understanding of the CHK2 signaling pathway, we have carried out a yeast two-hybrid screen to search for potential CHK2-interacting proteins. Here, we report the identification of the mitotic checkpoint kinase, TTK/hMps1, as a novel CHK2-interacting protein. TTK/hMps1 directly phosphorylates CHK2 on Thr-68 in vitro. Expression of a TTK kinase-dead mutant, TTK(D647A), interferes with the G(2)/M arrest induced by either ionizing radiation or UV light. Interestingly, induction of CHK2 Thr-68 phosphorylation and of several downstream events, such as cyclin B1 accumulation and Cdc2 Tyr-15 phosphorylation, is also affected. Furthermore, ablation of TTK expression using small interfering RNA results not only in reduced CHK2 Thr-68 phosphorylation, but also in impaired growth arrest. Our results are consistent with a model in which TTK functions upstream from CHK2 in response to DNA damage and suggest possible cross-talk between the spindle assembly checkpoint and the DNA damage checkpoint. |
| Databáze: | OpenAIRE |
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