Bcl-XL mutations suppress cellular sensitivity to antimycin A.
Article Details
- CitationCopy to clipboard
Manion MK, O'Neill JW, Giedt CD, Kim KM, Zhang KY, Hockenbery DM
Bcl-XL mutations suppress cellular sensitivity to antimycin A.
J Biol Chem. 2004 Jan 16;279(3):2159-65. Epub 2003 Oct 8.
- PubMed ID
- 14534311 [ View in PubMed]
- Abstract
Cells expressing high levels of the BCL-X(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(L), previously identified as an interface for dimerization to BAX and related proapoptotic proteins. Here, we identify BCL-X(L) hydrophobic groove mutants with normal cellular anti-apoptotic function but suppressed sensitivity to AA. The LD(50) of AA for cells expressing BCL-X(L) mutants directly correlates with the measured in vitro dissociation constants for AA binding. These results indicate that BCL-X(L) is a principal target mediating AA cytotoxicity.