Down-regulation of DIAP1 triggers a novel Drosophila cell death pathway mediated by dark and DRONC

Tatsushi Igaki, Yuki Yamamoto-Goto, Naoko Tokushige, Hiroshi Kanda, Masayuki Miura

Research output: Contribution to journalArticle

58 Citations (Scopus)

Abstract

Members of the inhibitor of apoptosis protein (IAP) family can inhibit caspases and cell death in a variety of insect and vertebrate systems. Drosophila IAP1 (DIAP1) inhibits cell death to facilitate normal embryonic development. Here, using RNA interference, we showed that down-regulation of DIAP1 is sufficient to induce cell death in Drosophila S2 cells. Although this cell death process was accompanied by elevated caspase activity, this activation was not essential for cell death. We found that DIAP1 depletion-induced cell death was strongly suppressed by a reduction in the Drosophila caspase DRONC or the Drosophila apoptotic protease-activating factor-1 (Apaf-1) homolog, Dark. RNA interference studies in Drosophila embryos also demonstrated that the action of Dark is epistatic to that of DIAP1 in this cell death pathway. The cell death caused by down-regulation of DIAP1 was accelerated by overexpression of DRONC and Dark, and a caspase-inactive mutant form of DRONC could functionally substitute the wild-type DRONC in accelerating cell death. These results suggest the existence of a novel mechanism for cell death signaling in Drosophila that is mediated by DRONC and Dark.

Original languageEnglish
Pages (from-to)23103-23106
Number of pages4
JournalJournal of Biological Chemistry
Volume277
Issue number26
DOIs
Publication statusPublished - 2002 Jun 28
Externally publishedYes

Fingerprint

Cell death
Drosophila
Cell Death
Down-Regulation
Caspases
RNA Interference
Apoptotic Protease-Activating Factor 1
RNA
Inhibitor of Apoptosis Proteins
Embryonic Development
Insects
Vertebrates
Embryonic Structures
Chemical activation

ASJC Scopus subject areas

  • Biochemistry

Cite this

Down-regulation of DIAP1 triggers a novel Drosophila cell death pathway mediated by dark and DRONC. / Igaki, Tatsushi; Yamamoto-Goto, Yuki; Tokushige, Naoko; Kanda, Hiroshi; Miura, Masayuki.

In: Journal of Biological Chemistry, Vol. 277, No. 26, 28.06.2002, p. 23103-23106.

Research output: Contribution to journalArticle

Igaki, Tatsushi ; Yamamoto-Goto, Yuki ; Tokushige, Naoko ; Kanda, Hiroshi ; Miura, Masayuki. / Down-regulation of DIAP1 triggers a novel Drosophila cell death pathway mediated by dark and DRONC. In: Journal of Biological Chemistry. 2002 ; Vol. 277, No. 26. pp. 23103-23106.
@article{2416e4eda6a04c00b735be8328d29b3c,
title = "Down-regulation of DIAP1 triggers a novel Drosophila cell death pathway mediated by dark and DRONC",
abstract = "Members of the inhibitor of apoptosis protein (IAP) family can inhibit caspases and cell death in a variety of insect and vertebrate systems. Drosophila IAP1 (DIAP1) inhibits cell death to facilitate normal embryonic development. Here, using RNA interference, we showed that down-regulation of DIAP1 is sufficient to induce cell death in Drosophila S2 cells. Although this cell death process was accompanied by elevated caspase activity, this activation was not essential for cell death. We found that DIAP1 depletion-induced cell death was strongly suppressed by a reduction in the Drosophila caspase DRONC or the Drosophila apoptotic protease-activating factor-1 (Apaf-1) homolog, Dark. RNA interference studies in Drosophila embryos also demonstrated that the action of Dark is epistatic to that of DIAP1 in this cell death pathway. The cell death caused by down-regulation of DIAP1 was accelerated by overexpression of DRONC and Dark, and a caspase-inactive mutant form of DRONC could functionally substitute the wild-type DRONC in accelerating cell death. These results suggest the existence of a novel mechanism for cell death signaling in Drosophila that is mediated by DRONC and Dark.",
author = "Tatsushi Igaki and Yuki Yamamoto-Goto and Naoko Tokushige and Hiroshi Kanda and Masayuki Miura",
year = "2002",
month = "6",
day = "28",
doi = "10.1074/jbc.C200222200",
language = "English",
volume = "277",
pages = "23103--23106",
journal = "Journal of Biological Chemistry",
issn = "0021-9258",
publisher = "American Society for Biochemistry and Molecular Biology Inc.",
number = "26",

}

TY - JOUR

T1 - Down-regulation of DIAP1 triggers a novel Drosophila cell death pathway mediated by dark and DRONC

AU - Igaki, Tatsushi

AU - Yamamoto-Goto, Yuki

AU - Tokushige, Naoko

AU - Kanda, Hiroshi

AU - Miura, Masayuki

PY - 2002/6/28

Y1 - 2002/6/28

N2 - Members of the inhibitor of apoptosis protein (IAP) family can inhibit caspases and cell death in a variety of insect and vertebrate systems. Drosophila IAP1 (DIAP1) inhibits cell death to facilitate normal embryonic development. Here, using RNA interference, we showed that down-regulation of DIAP1 is sufficient to induce cell death in Drosophila S2 cells. Although this cell death process was accompanied by elevated caspase activity, this activation was not essential for cell death. We found that DIAP1 depletion-induced cell death was strongly suppressed by a reduction in the Drosophila caspase DRONC or the Drosophila apoptotic protease-activating factor-1 (Apaf-1) homolog, Dark. RNA interference studies in Drosophila embryos also demonstrated that the action of Dark is epistatic to that of DIAP1 in this cell death pathway. The cell death caused by down-regulation of DIAP1 was accelerated by overexpression of DRONC and Dark, and a caspase-inactive mutant form of DRONC could functionally substitute the wild-type DRONC in accelerating cell death. These results suggest the existence of a novel mechanism for cell death signaling in Drosophila that is mediated by DRONC and Dark.

AB - Members of the inhibitor of apoptosis protein (IAP) family can inhibit caspases and cell death in a variety of insect and vertebrate systems. Drosophila IAP1 (DIAP1) inhibits cell death to facilitate normal embryonic development. Here, using RNA interference, we showed that down-regulation of DIAP1 is sufficient to induce cell death in Drosophila S2 cells. Although this cell death process was accompanied by elevated caspase activity, this activation was not essential for cell death. We found that DIAP1 depletion-induced cell death was strongly suppressed by a reduction in the Drosophila caspase DRONC or the Drosophila apoptotic protease-activating factor-1 (Apaf-1) homolog, Dark. RNA interference studies in Drosophila embryos also demonstrated that the action of Dark is epistatic to that of DIAP1 in this cell death pathway. The cell death caused by down-regulation of DIAP1 was accelerated by overexpression of DRONC and Dark, and a caspase-inactive mutant form of DRONC could functionally substitute the wild-type DRONC in accelerating cell death. These results suggest the existence of a novel mechanism for cell death signaling in Drosophila that is mediated by DRONC and Dark.

UR - http://www.scopus.com/inward/record.url?scp=0037189566&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0037189566&partnerID=8YFLogxK

U2 - 10.1074/jbc.C200222200

DO - 10.1074/jbc.C200222200

M3 - Article

C2 - 12011068

AN - SCOPUS:0037189566

VL - 277

SP - 23103

EP - 23106

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

SN - 0021-9258

IS - 26

ER -