Modulation of cell death by Bcl-x(L) through caspase interaction Academic Article Article uri icon


MeSH Major

  • Apoptosis
  • Apoptosis Regulatory Proteins
  • Carcinoma, Non-Small-Cell Lung
  • Drug Resistance, Neoplasm
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive
  • Lung Neoplasms
  • Membrane Proteins
  • Polymorphism, Genetic
  • Protein Kinase Inhibitors
  • Proto-Oncogene Proteins
  • Sequence Deletion


  • The caspases are cysteine proteases that have been implicated in the execution of programmed cell death in organisms ranging from nematodes to humans. Many members of the Bcl-2 family, including Bcl-XL, are potent inhibitors of programmed cell death and inhibit activation of caspases in cells. Here, we report a direct interaction between caspases and Bcl-XL. The loop domain of Bcl-XL is cleaved by caspases in vitro and in cells induced to undergo apoptotic death after Sindbis virus infection or interleukin 3 withdrawal. Mutation of the caspase cleavage site in Bcl-XL in conjunction with a mutation in the BH1 homology domain impairs the death-inhibitory activity of Bcl-XL, suggesting that interaction of Bcl-XL with caspases may be an important mechanism of inhibiting cell death. However, once Bcl-XL is cleaved, the C-terminal fragment of Bcl-XL potently induces apoptosis. Taken together, these findings indicate that the recognition/cleavage site of Bcl-XL may facilitate protection against cell death by acting at the level of caspase activation and that cleavage of Bcl-XL during the execution phase of cell death converts Bcl-XL from a protective to a lethal protein.

publication date

  • March 5, 1998



  • Academic Article


Digital Object Identifier (DOI)

  • 10.1073/pnas.95.2.554

PubMed ID

  • 9435230

Additional Document Info

start page

  • 554

end page

  • 9


  • 95


  • 2