DFF45/ICAD can be directly processed by granzyme B during the induction of apoptosis

Dori A. Thomas, Chunying Du, Ming Xu, Xiaodong Wang, Timothy J. Ley

Research output: Contribution to journalArticle

160 Scopus citations

Abstract

Granzyme B (GzmB) is a component of cytotoxic lymphocyte granules that can rapidly initiate apoptosis in target cells. While several procaspases are cleaved and activated by GzmB, the absolute requirement of caspase activation for GzmB-induced apoptosis is controversial. In this report, we demonstrate that GzmB can initiate apoptosis in the absence of caspase-3 activity by directly cleaving DFF45/ICAD to liberate activated DFF40/CAD. DFF45/ICAD cleavage occurs less efficiently in cells that lack caspase-3 activity, suggesting that the caspases normally amplify the GzmB death signal. DFF45/ICAD-deficient mouse embryo fibroblasts are partially resistant to GzmB-induced death, demonstrating the biological importance of DFF45/ICAD for GzmB-mediated apoptosis.

Original languageEnglish
Pages (from-to)621-632
Number of pages12
JournalImmunity
Volume12
Issue number6
DOIs
StatePublished - Jan 1 2000

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