Fig. 8: Scheme indicating the mechanism of Cat D inhibition-induced sensitizing effect on anticancer drugs via activation of NF-κB signaling. | Cell Death & Disease

Fig. 8: Scheme indicating the mechanism of Cat D inhibition-induced sensitizing effect on anticancer drugs via activation of NF-κB signaling.

From: Itch and autophagy-mediated NF-κB activation contributes to inhibition of cathepsin D-induced sensitizing effect on anticancer drugs

Fig. 8

Two molecular mechanisms are associated with autophagy-mediated IκB degradation by Cat D inhibition. First, depletion of Cat D phosphorylates Itch at T222 through activation of JNK signaling. Second, LKB1-mediated AMPK activation by Cat D inhibition phosphorylates ULK1 at S777, while ULK1 at S757 is dephosphorylated by inhibition of mTOR signaling. Subsequently, autophagy-dependent IκB degradation is involved in Cat D inhibition-mediated sensitizing effect to anticancer drugs through RNF183-dependent Bcl-xL downregulation.

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