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BID, a pro-apoptotic Bcl-2 family member, promotes cytochrome c release during apoptosis initiated by CD95L or TNF. Activation of caspase-8 in the latter pathways results in cleavage of BID, translocation of activated BID to mitochondria, followed by redistribution of cytochrome c to the cytosol. However, it is unclear whether BID participates in cytochrome c release in other (non-death receptor) cell death pathways. Here, we show that BID is cleaved in response to multiple death-inducing stimuli (staurosporine, UV radiation, cycloheximide, etoposide). However BID cleavage in these contexts was blocked by Bcl-2, suggesting that proteolysis of BID occurred distal to cytochrome c release. Furthermore, addition of cytochrome c to Jurkat post-nuclear extracts triggered breakdown of BID at Asp-59 which was catalysed by caspase-3 rather than caspase-8. We provide evidence that caspase-3 catalysed cleavage of BID represents a feedback loop for the amplification of mitochondrial cytochrome c release during cytotoxic drug and UV radiation-induced apoptosis.

Original publication




Journal article


Cell death and differentiation

Publication Date





556 - 565


Molecular Cell Biology Laboratory, Department of Genetics, The Smurfit Institute, Trinity College, Dublin 2, Ireland.


Jurkat Cells, Tumor Cells, Cultured, Mitochondria, Liver, Cell-Free System, Animals, Humans, Mice, Staurosporine, Cycloheximide, Etoposide, Cytochrome c Group, Caspases, Aspartic Acid, Carrier Proteins, Proto-Oncogene Proteins c-bcl-2, Enzyme Inhibitors, Nucleic Acid Synthesis Inhibitors, Protein Synthesis Inhibitors, Ultraviolet Rays, Apoptosis, Catalysis, BH3 Interacting Domain Death Agonist Protein, Caspase 3