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Drosophila morgue and the intersection between protein ubiquitination and programmed cell death

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Abstract

In Drosophila, cell survival decisions are mediated by the integrated functions of the Grim-Reaper death activators and Inhibitor-of-Apoptosis-Proteins (IAPs), such as DIAP1, to regulate caspase activities. We recently identified a gene that enhances the actions of the Grim-Reaper proteins and negatively regulates the levels of DIAP1 protein. This gene, morgue, encodes a novel protein that contains both an F box and a ubiquitin conjugase domain. Interestingly, the Morgue conjugase domain lacks the active site cysteine required for covalent linkage to ubiquitin. Morgue could target IAPs and other proteins for ubiquitination and proteasome-dependent turnover by acting either in an SCF ubiquitin E3 ligase complex, or as a ubiquitin E2 conjugase enzyme variant (UEV) in conjunction with a catalytically active E2 conjugase. Morgue is evolutionarily conserved, as a Morgue ortholog was identified from the mosquito, Anopheles gambiae. Elucidation of morgue function should provide novel insights into the mechanisms of ubiquitination and programmed cell death.

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  1. Biology Department, Program in Molecular and Cellular Biology, University of Massachusetts at Amherst, Amherst, MA, 01003, USA

    Barbara A. Schreader, Yiqin Wang & John R. Nambu

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  1. Barbara A. Schreader
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  2. Yiqin Wang
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Schreader, B.A., Wang, Y. & Nambu, J.R. Drosophila morgue and the intersection between protein ubiquitination and programmed cell death. Apoptosis 8, 129–139 (2003). https://doi.org/10.1023/A:1022914524601

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