Unrestrained caspase-dependent cell death caused by loss of Diap 1 function requires the Drosophila Apaf-1 homolog, Dark

Antony Rodriguez, Po Chen, Holt Oliver, John M. Abrams

Research output: Contribution to journalArticle

88 Citations (Scopus)

Abstract

In mammals and Drosophila, apoptotic caspases are under positive control via the CED-4/Apaf-1/Dark adaptors and negative control via IAPs (inhibitor of ns). However, the in vivo genetic relationship between these opposing regulators is not known. In this study, we demonstrate that a dark mutation reverses catastrophic defects seen in Diap1 mutants and rescues cells specified for Diap1regulated cell death in development and in response to genotoxic stress. We also find that dark function is required for hyperactivation of caspases which occurs in the absence of Diap1. Since the action of dark is epistatic to that of Diap1, these findings demonstrate that caspase-dependent cell death requires concurrent positive input through Apaf-1-like proteins together with disruption of IAP-caspase complexes.

Original languageEnglish (US)
Pages (from-to)2189-2197
Number of pages9
JournalEMBO Journal
Volume21
Issue number9
DOIs
StatePublished - May 1 2002

Fingerprint

Cell death
Caspases
Drosophila
Cell Death
Mammals
DNA Damage
Defects
Mutation
Proteins

Keywords

  • Apaf-1
  • Apoptosis
  • Drosophila
  • IAP
  • PCD

ASJC Scopus subject areas

  • Genetics
  • Cell Biology

Cite this

Unrestrained caspase-dependent cell death caused by loss of Diap 1 function requires the Drosophila Apaf-1 homolog, Dark. / Rodriguez, Antony; Chen, Po; Oliver, Holt; Abrams, John M.

In: EMBO Journal, Vol. 21, No. 9, 01.05.2002, p. 2189-2197.

Research output: Contribution to journalArticle

@article{6bf2436f6e2b4ba6a3977ec41bffe6e4,
title = "Unrestrained caspase-dependent cell death caused by loss of Diap 1 function requires the Drosophila Apaf-1 homolog, Dark",
abstract = "In mammals and Drosophila, apoptotic caspases are under positive control via the CED-4/Apaf-1/Dark adaptors and negative control via IAPs (inhibitor of ns). However, the in vivo genetic relationship between these opposing regulators is not known. In this study, we demonstrate that a dark mutation reverses catastrophic defects seen in Diap1 mutants and rescues cells specified for Diap1regulated cell death in development and in response to genotoxic stress. We also find that dark function is required for hyperactivation of caspases which occurs in the absence of Diap1. Since the action of dark is epistatic to that of Diap1, these findings demonstrate that caspase-dependent cell death requires concurrent positive input through Apaf-1-like proteins together with disruption of IAP-caspase complexes.",
keywords = "Apaf-1, Apoptosis, Drosophila, IAP, PCD",
author = "Antony Rodriguez and Po Chen and Holt Oliver and Abrams, {John M.}",
year = "2002",
month = "5",
day = "1",
doi = "10.1093/emboj/21.9.2189",
language = "English (US)",
volume = "21",
pages = "2189--2197",
journal = "EMBO Journal",
issn = "0261-4189",
publisher = "Nature Publishing Group",
number = "9",

}

TY - JOUR

T1 - Unrestrained caspase-dependent cell death caused by loss of Diap 1 function requires the Drosophila Apaf-1 homolog, Dark

AU - Rodriguez, Antony

AU - Chen, Po

AU - Oliver, Holt

AU - Abrams, John M.

PY - 2002/5/1

Y1 - 2002/5/1

N2 - In mammals and Drosophila, apoptotic caspases are under positive control via the CED-4/Apaf-1/Dark adaptors and negative control via IAPs (inhibitor of ns). However, the in vivo genetic relationship between these opposing regulators is not known. In this study, we demonstrate that a dark mutation reverses catastrophic defects seen in Diap1 mutants and rescues cells specified for Diap1regulated cell death in development and in response to genotoxic stress. We also find that dark function is required for hyperactivation of caspases which occurs in the absence of Diap1. Since the action of dark is epistatic to that of Diap1, these findings demonstrate that caspase-dependent cell death requires concurrent positive input through Apaf-1-like proteins together with disruption of IAP-caspase complexes.

AB - In mammals and Drosophila, apoptotic caspases are under positive control via the CED-4/Apaf-1/Dark adaptors and negative control via IAPs (inhibitor of ns). However, the in vivo genetic relationship between these opposing regulators is not known. In this study, we demonstrate that a dark mutation reverses catastrophic defects seen in Diap1 mutants and rescues cells specified for Diap1regulated cell death in development and in response to genotoxic stress. We also find that dark function is required for hyperactivation of caspases which occurs in the absence of Diap1. Since the action of dark is epistatic to that of Diap1, these findings demonstrate that caspase-dependent cell death requires concurrent positive input through Apaf-1-like proteins together with disruption of IAP-caspase complexes.

KW - Apaf-1

KW - Apoptosis

KW - Drosophila

KW - IAP

KW - PCD

UR - http://www.scopus.com/inward/record.url?scp=0036566395&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0036566395&partnerID=8YFLogxK

U2 - 10.1093/emboj/21.9.2189

DO - 10.1093/emboj/21.9.2189

M3 - Article

C2 - 11980716

AN - SCOPUS:0036566395

VL - 21

SP - 2189

EP - 2197

JO - EMBO Journal

JF - EMBO Journal

SN - 0261-4189

IS - 9

ER -