Figure 4.
GADD45-mediated cell cycle arrest and apoptosis. GADD45 inhibits the kinase activity of the CDK1/CyclinB1 complex and promotes G2/M arrest; interaction with p21waf/cip/mda-6 contributes to G1/S arrest. Interaction of GADD45 proteins with the N-terminal domain of MTK1 leads to relieve of its auto-inhibitory domain and activation of the kinase domain, which activates both p38 and JNK pathways and induces apoptosis. GADD45 proteins also participate in mitochondria-mediated apoptosis by interaction with EF1-α, which leads to cytoskeleton destabilization and to the release of Bim. As a consequence, Bim translocates into the mitochondria promoting release of cytochrome-c, resulting in the induction of apoptosis. GADD45 proteins inhibition is an essential step in the NF-κB-mediated cell survival.