BOLE FOR BCL-X(L) AS AN INHIBITOR OF CYTOSOLIC CYTOCHROME-C ACCUMULATION IN DNA DAMAGE-INDUCED APOPTOSIS

Cytochrome C is a mitochondrial protein that induces apoptosis when re leased into the cytosol or when added to cell-free extracts, Here we s how that cells that overpress the Bcl-2-related protein Bcl-x(L) fail to accumulate cytosolic cytochrome C or undergo apoptosis in response to genotoxic stress, Coimmunoprecipitation studies demonstrate that Bc l-x(L) associates with cytochrome C. Cytochrome C binds directly and s pecifically to Bcl-x(L) and not to the proapoptotic Bcl-x(s) protein, The results also demonstrate that Bcl-x(s) blocks binding of cytochrom e C to Bcl-x(L). Our findings support a role for Bcl-x(L) in protectin g cells from apoptosis by inhibiting the availability of cytochrome C in the cytosol.