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. 2023 Apr 18;14:1178337. doi: 10.3389/fimmu.2023.1178337

Figure 2.

Figure 2

Comparison of the Death Inducing Signaling Complex (DISC) and the complex formed during differentiation of monocytes (NADIC). During induction of extrinsic apoptosis, caspase-8 interacts with a death receptor (FAS, TRAIL) and FADD to form the DISC (Death-inducing signaling complex) at the cell membrane. The FLIP protein may also be present in the DISC to inhibit caspase-8 activity. Activation of caspase-8 leads to the cleavage of caspases-3 and -7 and then to the cleavage of numerous substrate proteins, ultimately inducing apoptosis of the cell. During the differentiation of monocytes into macrophages, CSF1R triggering leads to the activation of the AKT pathway, which is involved in the formation of an intracellular multimolecular complex including caspase-8, FLIP, FADD and RIP1 called non-apoptotic differentiation-inducing complex (NADIC). Within this complex, caspase-8 is activated and then cleaves caspases-3 and -7 to allow the cleavage of substrate proteins that are required for differentiation of monocytes into macrophages.