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Modulation of cell death by Bcl-XL through caspase interaction.

Publication ,  Journal Article
Clem, RJ; Cheng, EH; Karp, CL; Kirsch, DG; Ueno, K; Takahashi, A; Kastan, MB; Griffin, DE; Earnshaw, WC; Veliuona, MA; Hardwick, JM
Published in: Proc Natl Acad Sci U S A
January 20, 1998

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.

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Published In

Proc Natl Acad Sci U S A

DOI

ISSN

0027-8424

Publication Date

January 20, 1998

Volume

95

Issue

2

Start / End Page

554 / 559

Location

United States

Related Subject Headings

  • bcl-X Protein
  • Signal Transduction
  • Proto-Oncogene Proteins c-bcl-2
  • Mutation
  • Humans
  • Escherichia coli
  • Enzyme Activation
  • Cysteine Endopeptidases
  • Cell Line
  • Apoptosis
 

Citation

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Clem, R. J., Cheng, E. H., Karp, C. L., Kirsch, D. G., Ueno, K., Takahashi, A., … Hardwick, J. M. (1998). Modulation of cell death by Bcl-XL through caspase interaction. Proc Natl Acad Sci U S A, 95(2), 554–559. https://doi.org/10.1073/pnas.95.2.554
Clem, R. J., E. H. Cheng, C. L. Karp, D. G. Kirsch, K. Ueno, A. Takahashi, M. B. Kastan, et al. “Modulation of cell death by Bcl-XL through caspase interaction.Proc Natl Acad Sci U S A 95, no. 2 (January 20, 1998): 554–59. https://doi.org/10.1073/pnas.95.2.554.
Clem RJ, Cheng EH, Karp CL, Kirsch DG, Ueno K, Takahashi A, et al. Modulation of cell death by Bcl-XL through caspase interaction. Proc Natl Acad Sci U S A. 1998 Jan 20;95(2):554–9.
Clem, R. J., et al. “Modulation of cell death by Bcl-XL through caspase interaction.Proc Natl Acad Sci U S A, vol. 95, no. 2, Jan. 1998, pp. 554–59. Pubmed, doi:10.1073/pnas.95.2.554.
Clem RJ, Cheng EH, Karp CL, Kirsch DG, Ueno K, Takahashi A, Kastan MB, Griffin DE, Earnshaw WC, Veliuona MA, Hardwick JM. Modulation of cell death by Bcl-XL through caspase interaction. Proc Natl Acad Sci U S A. 1998 Jan 20;95(2):554–559.
Journal cover image

Published In

Proc Natl Acad Sci U S A

DOI

ISSN

0027-8424

Publication Date

January 20, 1998

Volume

95

Issue

2

Start / End Page

554 / 559

Location

United States

Related Subject Headings

  • bcl-X Protein
  • Signal Transduction
  • Proto-Oncogene Proteins c-bcl-2
  • Mutation
  • Humans
  • Escherichia coli
  • Enzyme Activation
  • Cysteine Endopeptidases
  • Cell Line
  • Apoptosis