Bcl-XL cooperatively associates with the Bap31 complex in the endoplasmic reticulum, dependent on procaspase-8 and Ced-4 adaptor

Bap31 is a polytopic integral membrane protein of the endoplasmic reticulum and forms a complex with Bcl-2/Bcl-X-L, and procaspase-8 (Ng, F., W., H.,, Nguyen, M.,, Kwan, T.,, Branton, P., E.,, Nicholson, W., D.,, Cromlish, J., A., and Shore, G., C., (1997) J., Cell Biol. 139, 327-338), In co-transfected human cells, procaspase-8 is capable of interacting with Ced-4, an important adaptor molecule in Caenorhabditis elegans that binds to and activates the C. elegans procaspase, proCed-3., Here, we show that the predicted death effector homology domain within the cytosolic region of Bap31 interacts with Ced-4 and contributes to recruitment of procaspase-8. Bcl-X-L,, which binds directly but weakly to the polytopic transmembrane region of Bap31, indirectly and cooperatively associates with the Bap31 cytosolic domain, dependent on the presence of procaspase-8 and Ced-4. Ced-4 Delta c does not interact with Bcl-X-L but rather displaces it from Bap31, suggesting that an endogenous Ced-4-like adaptor is a normal constituent of the Bap31 complex and is required for stable association of Bcl-X-L, with Bap31 in vivo., These findings indicate that Bap31 is capable of recruiting essential components of a core death regulatory machinery.