c-FLIP links mTORC2 to apoptosis

TL;DRAbstract

Cellular FLICE inhibitory protein (c-FLIP), a truncated form of caspase-8 that lacks caspase enzymatic activity, primarily acts as a specific inhibitor of the extrinsic death receptor-mediated apoptotic pathway [1]. Typically, a death ligand (e.g., TRAIL) binds to its corresponding death receptor (e.g., DR5) to induce oligomerization of the receptors. This will lead to recruitment of the adaptor molecule, FADD, and the initiator caspase, pro-caspase-8, to form a death inducing-signaling complex (DISC). In the DISC, pro-caspase-8 undergoes autocleavage and activation. The active caspase-8 further activates effector caspases that lead to apoptotic death. c-FLIP competes with pro-caspase-8 for binding to FADD, thereby suppressing DISC formation and caspase-8 activation. Many studies have shown that elevated c-FLIP expression protects cells from death receptor-mediated apoptosis, whereas downregulation of c-FLIP by chemicals or siRNA sensitizes cells to death receptor-induced apoptosis. Th

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