Modulation of cell death by Bcl-XL through caspase interaction. Academic Article uri icon

Overview

abstract

  • 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

  • January 20, 1998

Research

keywords

  • Apoptosis
  • Cysteine Endopeptidases
  • Proto-Oncogene Proteins c-bcl-2
  • Signal Transduction

Identity

PubMed Central ID

  • PMC18458

Scopus Document Identifier

  • 0031930688

Digital Object Identifier (DOI)

  • 10.1073/pnas.95.2.554

PubMed ID

  • 9435230

Additional Document Info

volume

  • 95

issue

  • 2