DOI: 10.1083/jcb.149.3.623. Pro-Apoptotic Apoptosis Protease–Activating Factor 1 (Apaf-1) Has a Cytoplasmic Localization Distinct from Bcl-2 or Bcl-XL

Pro-Apoptotic Apoptosis Protease–Activating Factor 1 (Apaf-1) Has a Cytoplasmic Localization Distinct from Bcl-2 or Bcl-XL

10.1083/jcb.149.3.623

Crossref journal-article

Rockefeller University Press

The Journal of Cell Biology (291)

Abstract

How Bcl-2 and its pro-survival relatives prevent activation of the caspases that mediate apoptosis is unknown, but they appear to act through the caspase activator apoptosis protease–activating factor 1 (Apaf-1). According to the apoptosome model, the Bcl-2–like proteins preclude Apaf-1 activity by sequestering the protein. To explore Apaf-1 function and to test this model, we generated monoclonal antibodies to Apaf-1 and used them to determine its localization within diverse cells by subcellular fractionation and confocal laser scanning microscopy. Whereas Bcl-2 and Bcl-xL were prominent on organelle membranes, endogenous Apaf-1 was cytosolic and did not colocalize with them, even when these pro-survival proteins were overexpressed or after apoptosis was induced. Immunogold electron microscopy confirmed that Apaf-1 was dispersed in the cytoplasm and not on mitochondria or other organelles. After the death stimuli, Bcl-2 and Bcl-xL precluded the release of the Apaf-1 cofactor cytochrome c from mitochondria and the formation of larger Apaf-1 complexes, which are steps that presage apoptosis. However, neither Bcl-2 nor Bcl-xL could prevent the in vitro activation of Apaf-1 induced by the addition of exogenous cytochrome c. Hence, rather than sequestering Apaf-1 as proposed by the apoptosome model, Bcl-2–like proteins probably regulate Apaf-1 indirectly by controlling upstream events critical for its activation.

Bibliography

Hausmann, G., OâReilly, L. A., van Driel, R., Beaumont, J. G., Strasser, A., Adams, J. M., & Huang, D. C. S. (2000). Pro-Apoptotic Apoptosis ProteaseâActivating Factor 1 (Apaf-1) Has a Cytoplasmic Localization Distinct from Bcl-2 or Bcl-XL. The Journal of Cell Biology, 149(3), 623â634.

Authors 7

George Hausmann (first)
Lorraine A. O'Reilly (additional)
Rosemary van Driel (additional)
Jennifer G. Beaumont (additional)
Andreas Strasser (additional)
Jerry M. Adams (additional)
David C.S. Huang (additional)

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Dates

Type	When
Created	23 years, 1 month ago (July 26, 2002, 12:45 p.m.)
Deposited	2 years, 1 month ago (July 28, 2023, 10:23 p.m.)
Indexed	3 months, 2 weeks ago (May 18, 2025, 12:22 p.m.)
Issued	25 years, 4 months ago (May 1, 2000)
Published	25 years, 4 months ago (May 1, 2000)
Published Online	25 years, 4 months ago (May 1, 2000)
Published Print	25 years, 4 months ago (May 1, 2000)

Funders 0

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BibTeX

@article{Hausmann_2000, title={Pro-Apoptotic Apoptosis Protease–Activating Factor 1 (Apaf-1) Has a Cytoplasmic Localization Distinct from Bcl-2 or Bcl-XL}, volume={149}, ISSN={1540-8140}, url={http://dx.doi.org/10.1083/jcb.149.3.623}, DOI={10.1083/jcb.149.3.623}, number={3}, journal={The Journal of Cell Biology}, publisher={Rockefeller University Press}, author={Hausmann, George and O’Reilly, Lorraine A. and van Driel, Rosemary and Beaumont, Jennifer G. and Strasser, Andreas and Adams, Jerry M. and Huang, David C.S.}, year={2000}, month=may, pages={623–634} }

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