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), 658-665. (doi:10.1006/bbrc.1996.1565). (PMID:8885990).
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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.
|Subjects:||Q Science > QD Chemistry
Q Science > QR Microbiology > QR180 Immunology
Q Science > QH Natural history > QH301 Biology
|Divisions:||University Structure - Pre August 2011 > School of Medicine > Cancer Sciences
|Date Deposited:||04 Oct 2010 13:38|
|Last Modified:||01 Jun 2011 03:17|
|Contributors:||Froelich, Christopher J. (Author)
Hanna, William L. (Author)
Poirier, Guy G. (Author)
Duriez, Patrick J. (Author)
D'Amours, Damien (Author)
Salvesen, Guy S. (Author)
Alnemri, Emad S. (Author)
Earnshaw, William C. (Author)
Shah, Girish M. (Author)
|Date:||23 October 1996|
|RDF:||RDF+N-Triples, RDF+N3, RDF+XML, Browse.|
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