Jafrac2 is an IAP antagonist that promotes cell death by liberating Dronc from DIAP1

Jafrac2 is an IAP antagonist that promotes cell death by liberating Dronc from DIAP1 Members of the Inhibitor of Apoptosis Protein (IAP) family are essential for cell survival in Drosophila and appear to neutralize the cell death machinery by binding to and ubiquitylating pro‐apoptotic caspases. Cell death is triggered when ‘Reaper‐like’ proteins bind to IAPs and liberate caspases from IAPs. We have identified the thioredoxin peroxidase Jafrac2 as an IAP‐interacting protein in Drosophila cells that harbours a conserved N‐terminal IAP‐binding motif. In healthy cells, Jafrac2 resides in the endoplasmic reticulum but is rapidly released into the cytosol following induction of apoptosis. Mature Jafrac2 interacts genetically and biochemically with DIAP1 and promotes cell death in tissue culture cells and the Drosophila developing eye. In common with Rpr, Jafrac2‐mediated cell death is contingent on DIAP1 binding because mutations that abolish the Jafrac2–DIAP1 interaction suppress the eye phenotype caused by Jafrac2 expression. We show that Jafrac2 displaces Dronc from DIAP1 by competing with Dronc for the binding of DIAP1, consistent with the idea that Jafrac2 triggers cell death by liberating Dronc from DIAP1‐mediated inhibition. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png The EMBO Journal Wiley

Jafrac2 is an IAP antagonist that promotes cell death by liberating Dronc from DIAP1

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Publisher
Wiley
Copyright
Copyright © 2013 Wiley Periodicals, Inc
ISSN
0261-4189
eISSN
1460-2075
DOI
10.1093/emboj/cdf530
Publisher site
See Article on Publisher Site

Abstract

Members of the Inhibitor of Apoptosis Protein (IAP) family are essential for cell survival in Drosophila and appear to neutralize the cell death machinery by binding to and ubiquitylating pro‐apoptotic caspases. Cell death is triggered when ‘Reaper‐like’ proteins bind to IAPs and liberate caspases from IAPs. We have identified the thioredoxin peroxidase Jafrac2 as an IAP‐interacting protein in Drosophila cells that harbours a conserved N‐terminal IAP‐binding motif. In healthy cells, Jafrac2 resides in the endoplasmic reticulum but is rapidly released into the cytosol following induction of apoptosis. Mature Jafrac2 interacts genetically and biochemically with DIAP1 and promotes cell death in tissue culture cells and the Drosophila developing eye. In common with Rpr, Jafrac2‐mediated cell death is contingent on DIAP1 binding because mutations that abolish the Jafrac2–DIAP1 interaction suppress the eye phenotype caused by Jafrac2 expression. We show that Jafrac2 displaces Dronc from DIAP1 by competing with Dronc for the binding of DIAP1, consistent with the idea that Jafrac2 triggers cell death by liberating Dronc from DIAP1‐mediated inhibition.

Journal

The EMBO JournalWiley

Published: Jan 1, 2002

Keywords: ; ; ;

References

  • The role of cytochrome c in caspase activation in Drosophila melanogaster cells
    Dorstyn, L; Read, S; Cakouros, D; Huh, JR; Hay, BA; Kumar, S
  • DIABLO promotes apoptosis by removing MIHA/XIAP from processed caspase 9
    Ekert, PG; Silke, J; Hawkins, CJ; Verhagen, AM; Vaux, DL
  • Induction of apoptosis by Drosophila reaper, hid and grim through inhibition of IAP function
    Goyal, L; McCall, K; Agapite, J; Hartwieg, E; Steller, H
  • Diverse domains of THREAD/DIAP1 are required to inhibit apoptosis induced by REAPER and HID in Drosophila
    Lisi, S; Mazzon, I; White, K
  • The Drosophila caspase DRONC is regulated by DIAP1
    Meier, P; Silke, J; Leevers, SJ; Evan, GI
  • Signal transduction from the endoplasmic reticulum to the cell nucleus
    Pahl, HL
  • Unrestrained caspase‐dependent cell death caused by loss of Diap1 function requires the Drosophila Apaf‐1 homolog, Dark
    Rodriguez, A; Chen, P; Oliver, H; Abrams, JM
  • Apoptosis: letting slip the dogs of war
    Wolf, BB; Green, DR

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