Proteolysis of Fodrin (Non-erythroid Spectrin) during Apoptosis (*)
- Seamus J. Martin(1)(§),
- Geraldine A. O'Brien(1),
- Walter K. Nishioka(1),
- Anne J. McGahon,
- Artin Mahboubi(1),
- Takaomi C. Saido(2) and
- Douglas R. Green(1)
- From the (1)Division of Cellular Immunology, La Jolla Institute for Allergy and Immunology, La Jolla, California 92037 and the
- (2)Department of Molecular Biology, Tokyo Metropolitan Institute of Medical Science, Honkomagome, Bunkyo-ku, Tokyo 113, Japan
- § To whom correspondence should be addressed: Division of Cellular Immunology, La Jolla Institute for Allergy and Immunology, 11149 N. Torrey Pines Rd., La Jolla, CA 92037. Tel.: 619-558-3500; Fax: 619-558-3525.
Abstract
Several recent studies have implicated proteases as important triggers of apoptosis. Thus far, substrates that are cleaved during apoptosis have been elusive. In this report we demonstrate that cleavage of α-fodrin (non-erythroid spectrin) accompanies apoptosis, induced by activation via the CD3/T cell receptor complex in a murine T cell hybridoma, ligation of the Fas (CD95) molecule on a human T cell lymphoma line and other Fas-expressing cells, or treatment of cells with staurosporine, dexamethasone, or synthetic ceramide. Furthermore, inhibition of activation-induced apoptosis by pretreatment of T hybridoma cells with antisense oligonucleotides directed against c-myc also inhibited fodrin proteolysis, confirming that this cleavage process is tightly coupled to apoptosis. Fodrin cleavage during apoptosis may have implications for the membrane blebbing seen during this process.
Footnotes
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↵* This research was supported by a Wellcome Trust International Travelling Fellowship (to S. J. M.) and National Institutes of Health Grant GM52735 and American Cancer Society Grant CB-82 (both to D. R. G.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore by hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
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↵1E. Gulbins, R. Bissonnette, A. Mahboubi, S. Martin, W. Nishioka, T. Brunner, G. Baier, G. Bitterlich-Baier, C. Byrd, F. Lang, R. Kolesnick, A. Altman, and D. R. Green, submitted for publication.
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↵2 The abbreviations used are:
- mAb
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monoclonal antibody
- PI
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propidium iodide.
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- Received January 10, 1995.
- © 1995 by The American Society for Biochemistry and Molecular Biology, Inc.
