MUDENG is cleaved by caspase-3 during TRAIL-induced cell death

• MUDENG is cleaved by caspase-3.
• The cleavage of MUDENG is an early event of TRAIL-induced cell death.
• MUDENG cleavage results in reduction of cell death induced by MUDENG.

MUDENG, also known as AP5M1, was originally identified as an adaptin domain-containing gene that induced cell death in lymphoma cell lines. However, little is known of the mechanism responsible for MUDENG-mediated cell death. In this study, we investigated MUDENG changes during TRAIL-induced cell death. We found that MUDENG is rapidly processed in response to TRAIL in Jurkat and BJAB cells with time line similar to that of caspase activation. Caspase-3-mediated MUDENG cleavage was confirmed by an in vitro cleavage assay using recombinant active caspase proteins. Caspase cleavage sites (D276 and D290) were located in the adaptin domain of MUDENG, and cleaved MUDENG showed the reduced killing activity. These results suggest that the adaptin domain plays a key role in MUDENG-mediated cell death.