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Citation
Shapiro, P.J., Hsu, H.H., Jung, H., Robbins, E.S., Ryoo, H.D. (2008). Regulation of the Drosophila apoptosome through feedback inhibition.  Nat. Cell Biol. 10(12): 1440--1446.
FlyBase ID
FBrf0206338
Publication Type
Research paper
Abstract

Apoptosis is induced by caspases, which are members of the cysteine protease family. Caspases are synthesized as inactive zymogens and initiator caspases first gain activity by associating with an oligomeric complex of their adaptor proteins, such as the apoptosome. Activated initiator caspases subsequently cleave and activate effector caspases. Although such a proteolytic cascade would predict that a small number of active caspases could irreversibly amplify caspase activity and trigger apoptosis, many cells can maintain moderate levels of caspase activity to perform non-apoptotic roles in cellular differentiation, shape change and migration. Here we show that the Drosophila melanogaster apoptosome engages in a feedback inhibitory loop, which moderates its activation level in vivo. Specifically, the adaptor protein Apaf-1 lowers the level of its associated initiator caspase Dronc, without triggering apoptosis. Conversely, Dronc lowers Apaf-1 protein levels. This mutual suppression depends on the catalytic site of Dronc and a caspase cleavage site within Apaf-1. Moreover, the Drosophila inhibitor of apoptosis protein 1 (Diap1) is required for this process. We speculate that this feedback inhibition allows cells to regulate the degree of caspase activation for apoptotic and non-apoptotic purposes.

PubMed ID
PubMed Central ID
PMC2617731 (PMC) (EuropePMC)
Related Publication(s)
Note

Staying alive: apoptosome feedback inhibition.
Steller, 2008, Nat. Cell Biol. 10(12): 1387--1388 [FBrf0206373]

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Secondary IDs
    Language of Publication
    English
    Additional Languages of Abstract
    Parent Publication
    Publication Type
    Journal
    Abbreviation
    Nat. Cell Biol.
    Title
    Nature Cell Biology
    Publication Year
    1999-
    ISBN/ISSN
    1465-7392 1476-4679
    Data From Reference