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Granzyme B/perforin-mediated apoptosis of Jurkat cells results in cleavage of poly(ADP-ribose) polymerase to the 89-kDa apoptotic fragment and less abundant 64-kDa fragment

Froelich, Christopher J., Hanna, William L., Poirier, Guy G., Duriez, Patrick J., D'Amours, Damien, Salvesen, Guy S., Alnemri, Emad S., Earnshaw, William C. and Shah, Girish M. (1996) Granzyme B/perforin-mediated apoptosis of Jurkat cells results in cleavage of poly(ADP-ribose) polymerase to the 89-kDa apoptotic fragment and less abundant 64-kDa fragment Biochemical and Biophysical Research Communications, 227, (3), pp. 658-665. (doi:10.1006/bbrc.1996.1565). (PMID:8885990).

Record type: Article

Abstract

Cytotoxic lymphocytes utilize granule associated serine proteases (granzymes) and perforin to induce apoptosis. Although the importance of granzyme B has been established by gene ablation experiments, biochemical events initiated by the granzyme remain enigmatic. We show here that exposure of Jurkat cells to granzyme B and perforin results in cleavage of poly(ADP-ribose) polymerase to an apoptotic 89 kDa fragment and to lesser amounts of a 64 kDa fragment. The 64 kDa fragment is produced directly by granzyme B while the 89 kDa fragment is presumably generated by activated ICE/Ced-3 proteases. Establishing the intracellular function of GrB in the apoptotic response, these results indicate that granzyme B enters perforin treated targets activating the ICE/Ced-3 family proteases which then cleave poly(ADP-ribose) polymerase to its apoptotic fragment. Intracellular granzyme B appears to be translocated to the nucleus where the protease directly cleaves poly(ADP-ribose) polymerase.

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Published date: 23 October 1996

Identifiers

Local EPrints ID: 164817
URI: http://eprints.soton.ac.uk/id/eprint/164817
ISSN: 0006-291X
PURE UUID: 744d53b8-b9a4-4104-b8a3-8f96cb599c17

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Date deposited: 04 Oct 2010 13:38
Last modified: 18 Jul 2017 12:28

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Contributors

Author: Christopher J. Froelich
Author: William L. Hanna
Author: Guy G. Poirier
Author: Patrick J. Duriez
Author: Damien D'Amours
Author: Guy S. Salvesen
Author: Emad S. Alnemri
Author: William C. Earnshaw
Author: Girish M. Shah

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