Figure 6 | Scientific Reports

Figure 6

From: CD157 signaling promotes survival of acute myeloid leukemia cells and modulates sensitivity to cytarabine through regulation of anti-apoptotic Mcl-1

Figure 6

Schematic representation of CD157-mediated survival in AML cells. CD157 binding to fibronectin in AML cells promotes structural and functional interaction of CD157 with specific integrins. This activates intracellular signals leading to phosphorylation of AKT, mTOR and its downstream substrates p70S6K, pS6 ribosomal protein, 4E-BP1, and ERK. In turn, phosphorylated AKT inactivates its major target GSK-3β, which loses its pro-apoptotic function and favors the stabilization of Mcl-1. The increased expression of Mcl-1 strengthens its ability to sequester Bim and Bak, thus precluding the Bak/Bax oligomerization at the mitochondrial outer membrane, which is required for cytochrome c release and is considered a key step in apoptosis. S63845 binds to the BH3-binding groove of Mcl-1 releasing Bim and Bak and enabling the activation of the Bax/Bak-dependent apoptotic pathway. This results in outer mitochondrial membrane permeabilization and release of cytochrome c into the cytosol leading to activation of the caspase cascade.

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