Fig. 8: Schematic representation of the signaling network sustaining NOTCH1-ICD levels and cell survival in CLL, as a potential therapeutic target. | Cell Death & Disease

Fig. 8: Schematic representation of the signaling network sustaining NOTCH1-ICD levels and cell survival in CLL, as a potential therapeutic target.

From: GSK3β is a critical, druggable component of the network regulating the active NOTCH1 protein and cell viability in CLL

Fig. 8

Constitutive NOTCH1-ICD levels and CLL cell survival are sustained by GSK3β inactivation, due to an impaired PP2A activity and a high AKT activation, which both induce S9-GSK3β phosphorylation (pS9-GSK3β). The increase in PP2A activity induced by the highly specific activator DT-061 or the inhibition of AKT with the AKTiX inhibitor enhance GSK3β activity, leading to a decrease in NOTCH1-ICD levels with a concomitant reduction in CLL cell survival.

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