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Failure of Bcl‐2 to block cytochrome c redistribution during TRAIL‐induced apoptosis
Author(s) -
Keogh Sinead A.,
Walczak Henning,
Bouchier-Hayes Lisa,
Martin Seamus J.
Publication year - 2000
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(00)01375-2
Subject(s) - cytochrome c , apoptosis , caspase , microbiology and biotechnology , mitochondrion , chemistry , apoptosome , intrinsic apoptosis , tumor necrosis factor alpha , mitochondrial apoptosis induced channel , programmed cell death , biology , biochemistry , immunology
Tumour necrosis factor (TNF)‐related apoptosis‐inducing ligand (TRAIL) is a member of the TNF family of cytokines that promotes apoptosis and NF‐κB activation. Here we show that recombinant hu‐TRAIL initiates the activation of multiple caspases, the loss of mitochondrial transmembrane potential, the cleavage of BID and the redistribution of mitochondrial cytochrome c . However, whereas Bcl‐2 efficiently blocked UV radiation‐induced cytochrome c release and consequent apoptosis of CEM cells, it failed to do either in the context of TRAIL treatment. Thus, TRAIL engages a death pathway that is at least partially routed via the mitochondria, but in contrast with other stimuli that engage this pathway, TRAIL‐induced cytochrome c release is not regulated by Bcl‐2.