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Bax-independent inhibition of apoptosis by Bcl-XL

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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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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