Switch #:
SWTI000516
Switch type:
Binary
Switch subtype:
Pre-translational

Description:
Alternative splicing removes the BIR-binding motif of Diablo homolog, mitochondrial (DIABLO), abrogating binding to Mitochondrial import receptor subunit TOM70 (TOMM70A). 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) Mitochondrial import receptor subunit TOM70 (TOMM70A)

Interactions
Interaction #1 DIABLO - TOMM70A

Interfaces
(1) ELM:TRG_MLS motif (1MAALKSWLSRSVTSFFRYRQCLCVPVVANFKKRCFSELIRPWHKTVTIGFGVTLC55) in Diablo homolog, mitochondrial (DIABLO)
(2) Tetratricopeptide repeat (114-578) in Mitochondrial import receptor subunit TOM70 (TOMM70A)

Interaction Regulation
Alternative splicing Abrogation of the Diablo homolog, mitochondrial (DIABLO) TRG_MLS motif - Mitochondrial import receptor subunit TOM70 (TOMM70A) Tetratricopeptide repeat interaction

References

(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)




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