DPP8/9 processing of human AK2 unmasks an IAP binding motif

AK2 is n-terminally processed by methionine aminopeptidases, N-terminal acetylation and DDP8/9 to become an active protein which is then sorted in the mitochondrial intermembrane space. We used peptide pull-downs of free and acetylated N-terminal peptides of AK2 from the different processing steps to identify binding partners by MS. We identified the inhibitor of apoptosis E3 ligase proteins (IAPs; BIRC2, 3, 6 and XIAP) as new binding partners for processed AK2 and show that they are responsible for AK2 degradation in the cytosol.