A central role for Bid in granzyme B-induced apoptosis.
Granzyme B, a protease released from cytotoxic lymphocytes, has been proposed to induce target cell death by cleaving and activating the pro-apoptotic Bcl-2 family member Bid. It has also been proposed that granzyme B can induce target cell death by activating caspases directly, by cleaving caspase substrates, and/or by cleaving several non-caspase substrates. The relative importance of Bid in granzyme B-induced cell death has therefore remained unclear. Here we report that cells isolated from various tissues of Bid-deficient mice were resistant to granzyme B-induced cell death. Consistent with the proposed role of Bid in regulating mitochondrial outer membrane permeabilization, cytochrome c remained in the mitochondria of Bid-deficient cells treated with granzyme B. Unlike wild type cells, Bid-deficient cells survived and were then able to proliferate normally, demonstrating the critical role for Bid in mediating granzyme B-induced apoptosis.
Waterhouse
Nigel J
NJ
Cancer Cell Death, Gene Regulation, and Immune Signaling Laboratories, Cancer Immunology Program, Peter MacCallum Cancer Centre, Locked Bag 1, A'Beckett Street, Melbourne, Victoria 8006. nigel.waterhouse@petermac.org
Sedelies
Karin A
KA
Browne
Kylie A
KA
Wowk
Michelle E
ME
Newbold
Andrea
A
Sutton
Vivien R
VR
Clarke
Chris J P
CJ
Oliaro
Jane
J
Lindemann
Ralph K
RK
Bird
Phillip I
PI
Johnstone
Ricky W
RW
Trapani
Joseph A
JA
D000818:Animals; D017209:Apoptosis; D051023:BH3 Interacting Domain Death Agonist Protein; D001854:Bone Marrow Cells / Q000166:cytology / Q000378:metabolism; D002352:Carrier Proteins / Q000502:physiology*; D016923:Cell Death; D049109:Cell Proliferation; D002478:Cells, Cultured; D002857:Chromium / Q000378:metabolism; D045304:Cytochromes c / Q000378:metabolism; D003712:Dendrites / Q000378:metabolism; D003713:Dendritic Cells; D004305:Dose-Response Relationship, Drug; D005347:Fibroblasts / Q000378:metabolism; D053804:Granzymes; D007425:Intracellular Membranes / Q000378:metabolism; D008214:Lymphocytes / Q000378:metabolism; D016393:Lymphoma, B-Cell / Q000378:metabolism; D008564:Membrane Potentials; D051379:Mice; D008810:Mice, Inbred C57BL; D008928:Mitochondria / Q000378:metabolism; D012697:Serine Endopeptidases / Q000378:metabolism*; D013997:Time Factors
D051023:BH3 Interacting Domain Death Agonist Protein; C494815:Bid protein, mouse; D002352:Carrier Proteins; D002857:Chromium; D045304:Cytochromes c; D053804:Granzymes; C509214:Gzmb protein, mouse; D012697:Serine Endopeptidases