Reaper-mediated inhibition of DIAP1-induced DTRAF1 degradation results in activation of JNK in Drosophila

Erina Kuranaga, Hirotaka Kanuka, Tatsushi Igaki, Kazunobu Sawamoto, Hidenori Ichijo, Hideyuki Okano, Masayuki Miura

Research output: Contribution to journalArticle

103 Citations (Scopus)

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-proteasome pathway.

Original languageEnglish
Pages (from-to)705-710
Number of pages6
JournalNature Cell Biology
Volume4
Issue number9
DOIs
Publication statusPublished - 2002 Sep

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Tumor Necrosis Factor Receptor-Associated Peptides and Proteins
Inhibitor of Apoptosis Proteins
Drosophila melanogaster
Drosophila
Phosphotransferases
Cell Death
Proteasome Endopeptidase Complex
Ubiquitin
MAP Kinase Kinase 4
MAP Kinase Kinase Kinases
Physiological Stress
Drosophila thread protein
Phenotype

ASJC Scopus subject areas

  • Cell Biology

Cite this

Reaper-mediated inhibition of DIAP1-induced DTRAF1 degradation results in activation of JNK in Drosophila. / Kuranaga, Erina; Kanuka, Hirotaka; Igaki, Tatsushi; Sawamoto, Kazunobu; Ichijo, Hidenori; Okano, Hideyuki; Miura, Masayuki.

In: Nature Cell Biology, Vol. 4, No. 9, 09.2002, p. 705-710.

Research output: Contribution to journalArticle

Kuranaga, Erina ; Kanuka, Hirotaka ; Igaki, Tatsushi ; Sawamoto, Kazunobu ; Ichijo, Hidenori ; Okano, Hideyuki ; Miura, Masayuki. / Reaper-mediated inhibition of DIAP1-induced DTRAF1 degradation results in activation of JNK in Drosophila. In: Nature Cell Biology. 2002 ; Vol. 4, No. 9. pp. 705-710.
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