A central role for Bid in granzyme B-induced apoptosis |
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Authors: | Waterhouse Nigel J Sedelies Karin A Browne Kylie A Wowk Michelle E Newbold Andrea Sutton Vivien R Clarke Chris J P Oliaro Jane Lindemann Ralph K Bird Phillip I Johnstone Ricky W Trapani Joseph A |
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Institution: | 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 |
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Abstract: | 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. |
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