AKT activation inhibits radiation-induced apoptosis via acinus gene regulation

The serine/threonine kinase AKT (protein kinase B, PKB) promotes cell survival by phosphorylating and inhibiting components of the intrinsic cell death machinery. AKT has been shown to be potently activated in response to a wide variety of growth factors and ionizing radiation (Soderlund et al., 2005). AKT predominantly localizes to the cytoplasm and translocates to the nucleus upon cellular stimulation (Lu et al.,, 1998). AKT regulation of apoptosis is correlated with the control of key downstream substrates within the nucleus. Acinus predominantly locates within the nucleus and is known to be a member of the apotosiss and slicing-associated protein (ASAP) complex (Schwerk et al., 2003). It was reported that AKT phosphorylated acinus and inhibits acinus proteolytic cleavage by caspases (Hu et al., 2005). Therefore, we investigated the role of AKT activation on cell survival and acinus regulation in response to ionizing radiation. Here, we show that AKT activation inhibits cell death during radiation-induced apoptosis through the regulation of acinus gene expression in normal human cells. In the present study, we examined the novel regulatory mechanism responsible for the radiation induced cell death in normal human cells and found that AKT activation is closely associated with the inhibition of ionizing radiation-induced cell death. In addition, we showed that AKT activation regulates acinus gene expression via NF-κB pathway. In conclusion, our data demonstrate that the AKT activation increases the expression of acinus via NF-κB pathway and then blocks ionizing radiation-induced cell death.