Granzyme B directly and efficiently cleaves several downstream caspase substrates: implications for CTL-induced apoptosis - PubMed (original) (raw)

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

F Andrade et al. Immunity. 1998 Apr.

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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.

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