論文 - 詳細
| RRC ID | 39641 |
|---|---|
| 著者 | Watabe M, Kakeya H, Onose R, Osada H. |
| タイトル | Activation of MST/Krs and c-Jun N-terminal kinases by different signaling pathways during cytotrienin A-induced apoptosis. |
| ジャーナル | J Biol Chem |
| Abstract |
We found that antitumor drugs such as cytotrienin A, camptothecin, taxol, and 5-fluorouracil induced the activation of a 36-kDa protein kinase (p36 myelin basic protein (MBP) kinase) during apoptosis in human promyelocytic leukemia HL-60 cells. This p36 MBP kinase, which phosphorylates MBP in an in-gel kinase assay, results from the caspase-3-mediated proteolytic cleavage of MST/Krs protein, a mammalian Ste20-like serine/threonine kinase. Herein the correlation between cytotrienin A-induced apoptosis and the activation of MST/Krs proteins was examined in human tumor cell lines, including leukemia-, lung-, epidermoid-, cervix-, stomach-, and brain-derived cell lines. In cytotrienin A-sensitive cell lines, we observed a strong activation of p36 MBP kinase by cleavage of the C-terminal regulatory domain of full-length MST/Krs proteins by caspase-3. When the kinase-inactive mutant form of MST/Krs protein was overexpressed in cytotrienin A-sensitive HL-60 cells, the cytotrienin A-induced apoptosis was partially inhibited. Because cytotrienin A also activated c-Jun N-terminal kinase, we examined the effect of the expression of dominant negative c-Jun on cytotrienin A-induced apoptosis. The expression of dominant negative c-Jun also partially inhibited cytotrienin A-induced apoptosis. Furthermore, coexpression of kinase-inactive MST/Krs protein and dominant negative c-Jun completely suppressed cytotrienin A-induced apoptosis. These findings suggest that the proteolytic activation of MST/Krs and c-Jun N-terminal kinase activation are involved in cytotrienin A-induced apoptosis in human tumor cell lines. |
| 巻・号 | 275(12) |
| ページ | 8766-71 |
| 公開日 | 2000-3-24 |
| DOI | 10.1074/jbc.275.12.8766 |
| PII | S0021-9258(18)30186-8 |
| PMID | 10722720 |
| MeSH | Antibiotics, Antineoplastic / pharmacology* Apoptosis* Calcium-Calmodulin-Dependent Protein Kinases / metabolism Caspase 3 Caspases / metabolism Glycogen Synthase Kinase 3 Humans JNK Mitogen-Activated Protein Kinases MAP Kinase Kinase Kinases* Mitogen-Activated Protein Kinases / metabolism* Models, Biological Protein Serine-Threonine Kinases / metabolism* Proto-Oncogene Proteins / metabolism Proto-Oncogene Proteins c-bcl-2 / metabolism Proto-Oncogene Proteins c-jun / metabolism Rifamycins / pharmacology* Signal Transduction Tumor Cells, Cultured / drug effects bcl-2-Associated X Protein |
| IF | 4.238 |
| 引用数 | 35 |
| WOS 分野 | BIOCHEMISTRY & MOLECULAR BIOLOGY |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | Wikipedia |
| 各媒体での言及数の合計 | 1 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | U-937 DE-4(RCB0435) WI-38 HeLa(RCB0007) |