Bcl-X sub(L) Mutations Suppress Cellular Sensitivity to Antimycin A

Cells expressing high levels of the BCL-X sub(L) anti-apoptotic protein are preferentially killed by the mitochondrial inhibitor antimycin A (AA). Computational modeling predicts a binding site for AA in the extended hydrophobic groove on BCL-X sub(L), previously identified as an interface for dimer...

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Published inThe Journal of biological chemistry Vol. 279; no. 3; pp. 2159 - 2165
Main Authors Manion, M K, O'Neill, J W, Giedt, C D, Kim, K M, Zhang, KYZ, Hockenbery, D M
Format Journal Article
LanguageEnglish
Published 16.01.2004
Subjects
binding sites
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Summary:Cells expressing high levels of the BCL-X sub(L) anti-apoptotic protein are preferentially killed by the mitochondrial inhibitor antimycin A (AA). Computational modeling predicts a binding site for AA in the extended hydrophobic groove on BCL-X sub(L), previously identified as an interface for dimerization to BAX and related proapoptotic proteins. Here, we identify BCL- X sub(L) hydrophobic groove mutants with normal cellular anti-apoptotic function but suppressed sensitivity to AA. The LD sub(50) of AA for cells expressing BCL- X sub(L) mutants directly correlates with the measured in vitro dissociation constants for AA binding. These results indicate that BCL-X sub(L) is a principal target mediating AA cytotoxicity.
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ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.M306021200