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Bax-independent inhibition of apoptosis by Bcl-XL

Nature volume 379, pages 554–556 (1996)Cite this article

Abstract

THE Bcl-2-related protein, Bcl-xL, has been shown to block apoptosis induced by a variety of stimuli1–5 and to be a stronger protector against apoptosis than Bcl-2 under certain circumstances2,5. Using site-specific mutagenesis, we show here that the amino-acid residues critical for protection of cells by Bcl-xL against Sindbis virus-induced apoptosis are clustered within the Bcl-2-homology regions 1 and 2 (BH1 and BH2 regions). The residues necessary for Bcl-xL function are not identical to those required for Bcl-2 function6. Although it has been suggested that heterodimerization between Bcl-xL and Bax is essential for the anti-death activity of Bcl-xL (refs 7,8), our results suggest that the interaction with Bax is not required for Bcl-xL to exert its death-repressing activity. Specific mutations that disrupt the ability of Bcl-xL to interact with Bax or Bak still preserve 70–80% of the anti-death activity of wild-type Bcl-xL.

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Authors and Affiliations

  1. Neurovirology Laboratories, Department of Neurology, Department of Pharmacology and Molecular Sciences, Meyer 6-181, Johns Hopkins School of Medicine, 600 North Wolfe Street, Baltimore, Maryland, 21287-7681, USA

    Emily H.-Y. Cheng & J. Marie Hardwick

  2. Department of Medicine, Columbia University College of Physicians and Surgeons, New York, New York, 10032, USA

    Beth Levine

  3. Howard Hughes Medical Institute and Departments of Medicine, Molecular Genetics and Cell Biology, University of Chicago, Chicago, llinois, 60637, USA

    Lawrence H. Boise & Craig B. Thompson

Authors
  1. Emily H.-Y. Cheng
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  2. Beth Levine
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  3. Lawrence H. Boise
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  4. Craig B. Thompson
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  5. J. Marie Hardwick
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Cheng, EY., Levine, B., Boise, L. et al. Bax-independent inhibition of apoptosis by Bcl-XL. Nature 379, 554–556 (1996). https://doi.org/10.1038/379554a0

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