Figure 4.

Protein interactions of XIAP. Well-described XIAP interactions are illustrated. BIR2 and its N-terminal linker region interact with and inhibit caspase-3 and caspase-7, whereas BIR3 inhibits caspase-9.^55–58 Inhibition of caspases by XIAP can be relieved by SMAC and Omi/HtrA2, which are released by the mitochondria after proapoptotic stimuli and interact with BIR2 and BIR3.^59–61 BIR1 and BIR2 also interact with TAB1 and RIP2, respectively.^63–65 The C-terminal RING finger domain of XIAP possesses E3 ubiquitin ligase function.^69,70 XIAP-mediated ubiquitination of proteins, such as COMMD1, results in the subsequent targeting of the protein for proteasomal degradation.⁷¹ Ubiquitination of other proteins, such as apoptosis-inducing factor, may serve to alter the function of the protein.⁷²