| 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
|
| リソース情報 |
| ショウジョウバエ |
DGRC#109845 |
