Failure of Bcl-2 to block cytochrome c redistribution during TRAIL-induced apoptosis

FEBS Lett. 2000 Apr 7;471(1):93-8. doi: 10.1016/s0014-5793(00)01375-2.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis Regulatory Proteins
  • Apoptosis*
  • Biological Transport
  • COS Cells
  • Caspases / metabolism
  • Cytochrome c Group / metabolism*
  • Drug Interactions
  • Enzyme Activation
  • Humans
  • Jurkat Cells
  • Membrane Glycoproteins / pharmacology*
  • Mitochondria / drug effects
  • Mitochondria / metabolism
  • Proto-Oncogene Proteins c-bcl-2 / pharmacology*
  • TNF-Related Apoptosis-Inducing Ligand
  • Tumor Necrosis Factor-alpha / pharmacology*


  • Apoptosis Regulatory Proteins
  • Cytochrome c Group
  • Membrane Glycoproteins
  • Proto-Oncogene Proteins c-bcl-2
  • TNF-Related Apoptosis-Inducing Ligand
  • TNFSF10 protein, human
  • Tumor Necrosis Factor-alpha
  • Caspases