Cbl‐b‐dependent degradation of FLIPL is involved in ATO‐induced autophagy in leukemic K562 and gastric cancer cells

Abstract Various molecular mechanisms are involved in the efficacy of arsenic trioxide (ATO) against malignant hematologic and some solid tumors. FLICE-like inhibitory protein (FLIP) is an inhibitor of apoptosis mediated by death receptors. In this study, we identified a new link between the down-regulation of cellular FLIP L and ATO-induced autophagy. ATO induced the degradation of FLIP L in K562 and MGC803 cells, which was mediated by the ubiquitin–proteasome pathway. Moreover, the casitas B-lineage lymphoma-b (Cbl-b) was involved in this process, which interacted with FLIP L and promoted proteasomal degradation of FLIP L . Our findings lead to a better understanding of the mechanism of action of ATO, and suggest that a novel signaling pathway is required for ATO-induced autophagy in K562 and MGC803 cells. Structured summary of protein interactions FLIP-L physically interacts with CBL-B by anti bait coimmunoprecipitation ( View interaction )