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Immunity. 1998 Apr;8(4):451-60.

Granzyme B directly and efficiently cleaves several downstream caspase substrates: implications for CTL-induced apoptosis.

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1
Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.

Abstract

Caspase-mediated proteolysis of downstream substrates is a critical element of the execution pathway common to all forms of apoptosis studied to date. While this caspase-dependent pathway is activated during cytotoxic lymphocyte granule-induced cell death, recent studies have also provided evidence for caspase-independent pathways. However, the mechanisms mediating these additional pathways have not been defined. The current study demonstrates that DNA-PKcs and NuMA are directly and efficiently cleaved by granzyme B in vitro and in vivo, generating unique substrate fragments not observed during other forms of apoptosis. This direct, caspase-independent ability of granzyme B to cleave downstream death substrates constitutes an apoptotic effector mechanism that is insensitive to inhibitors of the signaling or execution components of the endogenous apoptotic cascade.

PMID:
9586635
DOI:
10.1016/s1074-7613(00)80550-6
[Indexed for MEDLINE]
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