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Morgue mediates apoptosis in the Drosophila melanogaster retina by promoting degradation of DIAP1

Nature Cell Biology volume 4, pages 425–431 (2002)Cite this article

Abstract

Inhibitor of apoptosis proteins (IAPs) provide a critical barrier to inappropriate apoptotic cell death through direct binding and inhibition of caspases. We demonstrate that degradation of IAPs is an important mechanism for the initiation of apoptosis in vivo. Drosophila Morgue, a ubiquitin conjugase-related protein, promotes DIAP1 down-regulation in the developing retina to permit selective programmed cell death. Morgue complexes with DIAP1 in vitro and mediates DIAP1 degradation in a manner dependent on the Morgue UBC domain. Reaper (Rpr) and Grim, but not Hid, also promote the degradation of DIAP1 in vivo, suggesting that these proteins promote cell death through different mechanisms.

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Figure 1: Mutations in morgue impair apoptosis in the developing retina.
Figure 2: Mutations in morgue modify cell death phenotypes.
Figure 3: Morgue encodes an E2-related protein with conserved UBC and F-box domains.
Figure 4: Expression patterns of morgue.
Figure 5: The loss of cell death in morgue retinae is caused by post-translational elevation of DIAP1.
Figure 6: Morgue promotes DIAP1 for ubiquitin-mediated degradation in S2 cells.
Figure 7: Rpr, Grim and Hid differentially promote degradation of DIAP1 in vivo.

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Acknowledgements

We would like to especially thank J. Nambu for sharing data on the EP alleles and for naming the locus. The rabbit anti-DIAP1 antibody and HA–DIAP1 construct were a generous gift of K. White. This work was supported by the National Institutes of Health grant R01EY11495; R. Hays received support from NIH postdoctoral fellowship EY13507.

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  1. Department of Molecular Biology and Pharmacology, Washington University School of Medicine, 660 South Euclid Avenue; Campus Box 8103, Saint Louis, 63110, MO, USA

    Rebecca Hays, Laura Wickline & Ross Cagan

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Correspondence to Ross Cagan.

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Hays, R., Wickline, L. & Cagan, R. Morgue mediates apoptosis in the Drosophila melanogaster retina by promoting degradation of DIAP1. Nat Cell Biol 4, 425–431 (2002). https://doi.org/10.1038/ncb794

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