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Ditzel, M., Wilson, R., Tenev, T., Zachariou, A., Paul, A., Deas, E., Meier, P. (2003). Degradation of DIAP1 by the N-end rule pathway is essential for regulating apoptosis.  Nat. Cell Biol. 5(5): 467--473.
FlyBase ID
FBrf0159242
Publication Type
Research paper
Abstract

Some members of the inhibitor of apoptosis (IAP) protein family block apoptosis by binding to and neutralizing active caspases. We recently demonstrated that a physical association between IAP and caspases alone is insufficient to regulate caspases in vivo and that an additional level of control is provided by IAP-mediated ubiquitination of both itself and the associated caspases. Here we show that Drosophila IAP 1 (DIAP1) is degraded by the 'N-end rule' pathway and that this process is indispensable for regulating apoptosis. Caspase-mediated cleavage of DIAP1 at position 20 converts the more stable pro-N-degron of DIAP1 into the highly unstable, Asn-bearing, DIAP1 N-degron of the N-end rule degradation pathway. Thus, DIAP1 represents the first known metazoan substrate of the N-end rule pathway that is targeted for degradation through its amino-terminal Asn residue. We demonstrate that the N-end rule pathway is required for regulation of apoptosis induced by Reaper and Hid expression in the Drosophila melanogaster eye. Our data suggest that DIAP1 instability, mediated through caspase activity and subsequent exposure of the N-end rule pathway, is essential for suppression of apoptosis. We suggest that DIAP1 safeguards cell viability through the coordinated mutual destruction of itself and associated active caspases.

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Related Publication(s)
Review

The N-end rule and regulation of apoptosis.
Varshavsky, 2003, Nat. Cell Biol. 5(5): 373--376 [FBrf0161531]

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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
    Aberrations (2)
    Alleles (2)
    Genes (10)
    Transgenic Constructs (2)