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J. Biol. Chem., Vol. 279, Issue 35, 36923-36930, August 27, 2004

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Caspase-dependent Inactivation of Proteasome Function during Programmed Cell Death in Drosophila and Man^*

Colin Adrain, Emma M. Creagh, Sean P. Cullen, and Seamus J. Martin

From the Molecular Cell Biology Laboratory, Department of Genetics, The Smurfit Institute, Trinity College, Dublin 2, Ireland

The caspase family of cysteine proteases plays a conserved role in the coordinate demolition of cellular structures during programmed cell death from nematodes to man. Because cells undergoing programmed cell death in nematodes, flies, and mammals all share common features, this suggests that caspases target a common set of cellular structures in each of these organisms. However, although many substrates for mammalian caspases have been identified, few substrates for these proteases have been identified in invertebrates. To search for similarities between the repertoires of proteins targeted for proteolysis by caspases in flies and mammals, we have performed proteomics-based screens in Drosophila and human cell lines undergoing apoptosis. Here we show that several subunits of the proteasome undergo caspase-dependent proteolysis in both organisms and that this results in diminished activity of this multicatalytic protease complex. These data suggest that caspase-dependent proteolysis decreases protein turnover by the proteasome and that this is a conserved event in programmed cell death from Drosophila to mammals.

Received for publication, March 8, 2004 , and in revised form, June 9, 2004.

^* This work was supported by Science Foundation Ireland Grant PI1/B038. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

These authors contributed equally to this work and share first authorship.

To whom correspondence should be addressed. Tel.: 353-1-608-1289; Fax: 353-1-679-8558; E-mail: martinsj{at}tcd.ie.

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