Description:
Alternative splicing removes the BIR-binding motif of Diablo homolog, mitochondrial (DIABLO), abrogating binding to Baculoviral IAP repeat-containing protein 4 (XIAP). Isoform SMAC3 of Diablo homolog, mitochondrial (DIABLO) is localised to mitochondria via its mitochondrial localisation signal (MLS). Upon entry in mitochondria the MLS is cleaved and Isoform SMAC3 of Diablo homolog, mitochondrial (DIABLO) is found localised with cytochrome-c. During apoptosis, Isoform SMAC3 of Diablo homolog, mitochondrial (DIABLO) binds to the second/third BIR domain of Baculoviral IAP repeat-containing protein 4 (XIAP). This interaction disrupts binding of XIAP to processed Caspase-9 (CASP9) and promotes Caspase-3 (CASP3) activation. Isoform SMAC3 of Diablo homolog, mitochondrial (DIABLO) also promotes ubiquitination of XIAP and subsequent degradation. Isoform 1 of Diablo homolog, mitochondrial (DIABLO) on the other hand did not cause degradation of XIAP.
Participants:
(1) Diablo homolog, mitochondrial (DIABLO)
(2) Baculoviral IAP repeat-containing protein 4 (XIAP)
(1) Smac3, a novel Smac/DIABLO splicing variant, attenuates the stability and apoptosis-inhibiting activity of X-linked inhibitor of apoptosis protein.
Fu et al. J. Biol. Chem. (2003)
