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Bcr-Abl-mediated protection from apoptosis downstream of mitochondrial cytochrome c release.

Publication ,  Journal Article
Deming, PB; Schafer, ZT; Tashker, JS; Potts, MB; Deshmukh, M; Kornbluth, S
Published in: Molecular and cellular biology
December 2004

Bcr-Abl, activated in chronic myelogenous leukemias, is a potent cell death inhibitor. Previous reports have shown that Bcr-Abl prevents apoptosis through inhibition of mitochondrial cytochrome c release. We report here that Bcr-Abl also inhibits caspase activation after the release of cytochrome c. Bcr-Abl inhibited caspase activation by cytochrome c added to cell-free lysates and prevented apoptosis when cytochrome c was microinjected into intact cells. Bcr-Abl acted posttranslationally to prevent the cytochrome c-induced binding of Apaf-1 to procaspase 9. Although Bcr-Abl prevented interaction of endogenous Apaf-1 with the recombinant prodomain of caspase 9, it did not affect the association of endogenous caspase 9 with the isolated Apaf-1 caspase recruitment domain (CARD) or Apaf-1 lacking WD-40 repeats. These data suggest that Apaf-1 recruitment of caspase 9 is faulty in the presence of Bcr-Abl and that cytochrome c/dATP-induced exposure of the Apaf-1 CARD is likely defective. These data provide a novel locus of Bcr-Abl antiapoptotic action and suggest a distinct mechanism of apoptosomal inhibition.

Duke Scholars

Published In

Molecular and cellular biology

DOI

EISSN

1098-5549

ISSN

0270-7306

Publication Date

December 2004

Volume

24

Issue

23

Start / End Page

10289 / 10299

Related Subject Headings

  • Xenopus
  • Time Factors
  • Temperature
  • Recombinant Proteins
  • Rats
  • Proteins
  • Protein Structure, Tertiary
  • Protein Processing, Post-Translational
  • Protein Binding
  • Phosphotyrosine
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Deming, P. B., Schafer, Z. T., Tashker, J. S., Potts, M. B., Deshmukh, M., & Kornbluth, S. (2004). Bcr-Abl-mediated protection from apoptosis downstream of mitochondrial cytochrome c release. Molecular and Cellular Biology, 24(23), 10289–10299. https://doi.org/10.1128/mcb.24.23.10289-10299.2004
Deming, Paula B., Zachary T. Schafer, Jessica S. Tashker, Malia B. Potts, Mohanish Deshmukh, and Sally Kornbluth. “Bcr-Abl-mediated protection from apoptosis downstream of mitochondrial cytochrome c release.Molecular and Cellular Biology 24, no. 23 (December 2004): 10289–99. https://doi.org/10.1128/mcb.24.23.10289-10299.2004.
Deming PB, Schafer ZT, Tashker JS, Potts MB, Deshmukh M, Kornbluth S. Bcr-Abl-mediated protection from apoptosis downstream of mitochondrial cytochrome c release. Molecular and cellular biology. 2004 Dec;24(23):10289–99.
Deming, Paula B., et al. “Bcr-Abl-mediated protection from apoptosis downstream of mitochondrial cytochrome c release.Molecular and Cellular Biology, vol. 24, no. 23, Dec. 2004, pp. 10289–99. Epmc, doi:10.1128/mcb.24.23.10289-10299.2004.
Deming PB, Schafer ZT, Tashker JS, Potts MB, Deshmukh M, Kornbluth S. Bcr-Abl-mediated protection from apoptosis downstream of mitochondrial cytochrome c release. Molecular and cellular biology. 2004 Dec;24(23):10289–10299.

Published In

Molecular and cellular biology

DOI

EISSN

1098-5549

ISSN

0270-7306

Publication Date

December 2004

Volume

24

Issue

23

Start / End Page

10289 / 10299

Related Subject Headings

  • Xenopus
  • Time Factors
  • Temperature
  • Recombinant Proteins
  • Rats
  • Proteins
  • Protein Structure, Tertiary
  • Protein Processing, Post-Translational
  • Protein Binding
  • Phosphotyrosine