Failure of Bcl-2 to block cytochrome c redistribution during TRAIL-induced apoptosis.
Tumour necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is a member of the TNF family of cytokines that promotes apoptosis and NF-kappaB 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.
Keogh
S A
SA
Molecular Cell Biology Laboratory, Smurfit Institute of Genetics, Department of Genetics, Trinity College, Dublin, Ireland.
Walczak
H
H
Bouchier-Hayes
L
L
Martin
S J
SJ
D000818:Animals; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins; D001692:Biological Transport; D019556:COS Cells; D020169:Caspases / Q000378:metabolism; D003574:Cytochrome c Group / Q000378:metabolism*; D004347:Drug Interactions; D004789:Enzyme Activation; D006801:Humans; D019169:Jurkat Cells; D008562:Membrane Glycoproteins / Q000494:pharmacology*; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000494:pharmacology*; D053221:TNF-Related Apoptosis-Inducing Ligand; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D051017:Apoptosis Regulatory Proteins; D003574:Cytochrome c Group; D008562:Membrane Glycoproteins; D019253:Proto-Oncogene Proteins c-bcl-2; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human; D014409:Tumor Necrosis Factor-alpha; D020169:Caspases