Caspase-mediated cleavage of the exosome subunit PM/Scl-75 during apoptosis.
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| Abstract |
Recent studies have implicated the dying cell as a potential reservoir of modified autoantigens that might initiate and drive systemic autoimmunity in susceptible hosts. A number of subunits of the exosome, a complex of 3'-->5' exoribonucleases that functions in a variety of cellular processes, are recognized by the so-called anti-PM/Scl autoantibodies, found predominantly in patients suffering from an overlap syndrome of myositis and scleroderma. Here we show that one of these subunits, PM/Scl-75, is cleaved during apoptosis. PM/Scl-75 cleavage is inhibited by several different caspase inhibitors. The analysis of PM/Scl-75 cleavage by recombinant caspase proteins shows that PM/Scl-75 is efficiently cleaved by caspase-1, to a smaller extent by caspase-8, and relatively inefficiently by caspase-3 and caspase-7. Cleavage of the PM/Scl-75 protein occurs in the C-terminal part of the protein at Asp369 (IILD369 [see text] G), and at least a fraction of the resulting N-terminal fragments of PM/Scl-75 remains associated with the exosome. Finally, the implications of PM/Scl-75 cleavage for exosome function and the generation of anti-PM/Scl-75 autoantibodies are discussed.
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| Authors | Geurt Schilders, Reinout Raijmakers, Kelen C R Malmegrim, Lieselotte Vande Walle, Xavier Saelens, Wilma Vree Egberts, Walther J van Venrooij, Peter Vandenabeele, Ger J M Pruijn |
| Journal | Arthritis research & therapy (Arthritis Res Ther) Vol. 9 Issue 1 Pg. R12 ( 2007) ISSN: 1478-6362 [Electronic] England |
| PMID | 17280603 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't) |
| Chemical References |
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