Bax-independent inhibition of apoptosis by Bcl-XL

Emily H Y Cheng; Beth Levine; Lawrence H. Boise; Craig B. Thompson; J. Marie Hardwick

doi:10.1038/379554a0

Bax-independent inhibition of apoptosis by Bcl-X_L

Emily H Y Cheng, Beth Levine, Lawrence H. Boise, Craig B. Thompson, J. Marie Hardwick

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Abstract

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

Original language	English (US)
Pages (from-to)	554-556
Number of pages	3
Journal	Nature
Volume	379
Issue number	6565
DOIs	https://doi.org/10.1038/379554a0
State	Published - Feb 8 1996

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title = "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 Bax still preserve 70-80% of the anti-death activity of wild-type Bcl-xL.",

author = "Cheng, {Emily H Y} and Beth Levine and Boise, {Lawrence H.} and Thompson, {Craig B.} and Hardwick, {J. Marie}",

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T1 - Bax-independent inhibition of apoptosis by Bcl-XL

AU - Cheng, Emily H Y

AU - Levine, Beth

AU - Boise, Lawrence H.

AU - Thompson, Craig B.

AU - Hardwick, J. Marie

PY - 1996/2/8

Y1 - 1996/2/8

N2 - 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 Bax still preserve 70-80% of the anti-death activity of wild-type Bcl-xL.

AB - 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 Bax still preserve 70-80% of the anti-death activity of wild-type Bcl-xL.

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Bax-independent inhibition of apoptosis by Bcl-X_L

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