TY - JOUR
T1 - DFF45/ICAD can be directly processed by granzyme B during the induction of apoptosis
AU - Thomas, Dori A.
AU - Du, Chunying
AU - Xu, Ming
AU - Wang, Xiaodong
AU - Ley, Timothy J.
N1 - Funding Information:
This work was supported by National Institutes of Health grants DK49786 (T. J. L.) and T32HL07088 (D. A. T.). X. W. is supported by National Institutes of Health grants (GMR01-55942) and the Robert Welch Foundation (I-1412). M. Xu is supported by grants from National Alliance for Research on Schizophrenia and NIDA. We would like to thank Dr. Jianhua Zhang for genotyping the DFF45 mutant mice and thank Dr. R. A. Flavell and Dr. K. Roth for the caspase-3-deficient mice. We would like to thank A. Srinivasunan at IDUN pharmaceuticals for her generous gift of the anti-caspase-3 antibody (Csp3). We would like to thank Pam Goda and Kelly Schrimpf for expert animal husbandry, Elaine Ross for her expertise in MEF preparations, and Nancy Reidelberger for her assistance in the preparation of this manuscript. Finally, we would like to thank Dr. Peter A. Crawford for critical insight and support throughout this project.
PY - 2000
Y1 - 2000
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=0033673428&partnerID=8YFLogxK
U2 - 10.1016/S1074-7613(00)80213-7
DO - 10.1016/S1074-7613(00)80213-7
M3 - Article
C2 - 10894162
AN - SCOPUS:0033673428
SN - 1074-7613
VL - 12
SP - 621
EP - 632
JO - Immunity
JF - Immunity
IS - 6
ER -