Granzyme B directly and efficiently cleaves several downstream caspases substrates: Implications for CTL-induced apoptosis

Felipe Andrade, Sophie Roy, Donald Nicholson, Nancy Thornberry, Antony Rosen, Livia Casciola-Rosen

Research output: Contribution to journalArticle

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-PK(ca) 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 cleaved downstream death substrates constitutes an apoptotic effector mechanism that is insensitive to inhibitors of the signalling or execution components of the endogenous apoptotic cascade.

Original languageEnglish (US)
Pages (from-to)451-460
Number of pages10
JournalImmunity
Volume8
Issue number4
DOIs
StatePublished - Apr 1998

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ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

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