Fig. 3.

GSK3 regulates cell death, renewal, and differentiation. Active GSK3b increases mitochondrial permeability by phosphorylating proteins on the mitochondrial outer membrane. Subsequent release of cytochrome c triggers the intrinsic pathway leading to apoptosis. GSK3b also interacts with p53 and promotes cell cycle arrest and apoptosis. Inhibitory phosphorylation of GSK3b in response to insulin signaling promotes cell survival by blocking these pathways. Stem cell function is regulated in part through the activity of the WNT signaling pathway. GSK3b phosphorylates and targets beta-catenin for degradation in the absence of WNT signaling, blocking stem cell renewal