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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

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
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
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.
0006-291X
658-665
Froelich, Christopher J.
765f3ebe-95d9-4b8b-95d9-401910780713
Hanna, William L.
d08ab79a-6329-4970-b3bd-13195e9092d1
Poirier, Guy G.
5151b4a5-5657-412d-88c4-e3b9127ac42c
Duriez, Patrick J.
4cf499bc-007a-43b3-b180-d6e5dc3d151b
D'Amours, Damien
3332cdbc-ee2f-4f66-9cc0-401611ec9f45
Salvesen, Guy S.
0e825cdc-4ec4-42ff-8ac4-574f86a8dfdc
Alnemri, Emad S.
1c5d2b7e-8850-4167-85c4-e750f6da8037
Earnshaw, William C.
65e43de0-025a-46a5-8331-f30e02da4423
Shah, Girish M.
d2193a65-1589-446a-904e-d99f083cf6b6
Froelich, Christopher J.
765f3ebe-95d9-4b8b-95d9-401910780713
Hanna, William L.
d08ab79a-6329-4970-b3bd-13195e9092d1
Poirier, Guy G.
5151b4a5-5657-412d-88c4-e3b9127ac42c
Duriez, Patrick J.
4cf499bc-007a-43b3-b180-d6e5dc3d151b
D'Amours, Damien
3332cdbc-ee2f-4f66-9cc0-401611ec9f45
Salvesen, Guy S.
0e825cdc-4ec4-42ff-8ac4-574f86a8dfdc
Alnemri, Emad S.
1c5d2b7e-8850-4167-85c4-e750f6da8037
Earnshaw, William C.
65e43de0-025a-46a5-8331-f30e02da4423
Shah, Girish M.
d2193a65-1589-446a-904e-d99f083cf6b6

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), 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
ORCID for Patrick J. Duriez: ORCID iD orcid.org/0000-0003-1814-2552

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Date deposited: 04 Oct 2010 13:38
Last modified: 14 Mar 2024 02:52

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Contributors

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

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