論文 - 詳細
| RRC ID | 280 |
|---|---|
| 著者 | Kuranaga E, Kanuka H, Igaki T, Sawamoto K, Ichijo H, Okano H, Miura M. |
| タイトル | Reaper-mediated inhibition of DIAP1-induced DTRAF1 degradation results in activation of JNK in Drosophila. |
| ジャーナル | Nat Cell Biol |
| Abstract |
Although Jun amino-terminal kinase (JNK) is known to mediate a physiological stress signal that leads to cell death, the exact role of the JNK pathway in the mechanisms underlying intrinsic cell death is largely unknown. Here we show through a genetic screen that a mutant of Drosophila melanogaster tumour-necrosis factor receptor-associated factor 1 (DTRAF1) is a dominant suppressor of Reaper-induced cell death. We show that Reaper modulates the JNK pathway through Drosophila inhibitor-of-apoptosis protein 1 (DIAP1), which negatively regulates DTRAF1 by proteasome-mediated degradation. Reduction of JNK signals rescues the Reaper-induced small eye phenotype, and overexpression of DTRAF1 activates the Drosophila ASK1 (apoptosis signal-regulating kinase 1; a mitogen-activated protein kinase kinase kinase) and JNK pathway, thereby inducing cell death. Overexpresson of DIAP1 facilitates degradation of DTRAF1 in a ubiquitin-dependent manner and simultaneously inhibits activation of JNK. Expression of Reaper leads to a loss of DIAP1 inhibition of DTRAF1-mediated JNK activation in Drosophila cells. Taken together, our results indicate that DIAP1 may modulate cell death by regulating JNK activation through a ubiquitin#150;proteasome pathway. |
| 巻・号 | 4(9) |
| ページ | 705-10 |
| 公開日 | 2002-9-1 |
| DOI | 10.1038/ncb842 |
| PII | ncb842 |
| PMID | 12198495 |
| MeSH | Animals Animals, Genetically Modified Apoptosis Base Sequence Drosophila Proteins / genetics Drosophila Proteins / metabolism* Drosophila melanogaster / genetics Drosophila melanogaster / growth & development Drosophila melanogaster / metabolism* Enzyme Activation Eye / growth & development Genes, Insect Inhibitor of Apoptosis Proteins JNK Mitogen-Activated Protein Kinases MAP Kinase Kinase Kinase 5 MAP Kinase Kinase Kinases / genetics MAP Kinase Kinase Kinases / metabolism* Mitogen-Activated Protein Kinases / metabolism* Molecular Sequence Data Mutation Peptides / genetics Peptides / metabolism* Phenotype Proteins / metabolism* TNF Receptor-Associated Factor 1 |
| IF | 20.042 |
| 引用数 | 102 |
| WOS 分野 | CELL 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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| 各媒体での言及数の合計 | 0 |
| リソース情報 | |
| ショウジョウバエ | DGRC#109845 DGRC#119563 DGRC#119772 |