Fig. 6. Model for the dual role of the Akt/CDK2 pathway in cell cycle progression and cell death. In the presence of survival signal, PI3K activates Akt and the transiently activated Akt translocates to the nucleus only during late S and G2 phases and shuttles back to the cytoplasm. The transient nuclear Akt phosphorylates CDK2 in the nucleus at late S and G2 phases and leads to the temporary CDK2 relocation to the cytoplasm. When Akt is shuttled back to the cytoplasm, CDK2 rapidly translocates to the nucleus and helps in the cell cycle progression. But in the presence of selected apoptotic signals, PI3K constitutively activates Akt and leads to the constitutive nuclear Akt accumulation, where it phosphorylates CDK2. The constitutively phosphorylated CDK2 is sequestered in the cytoplasm and directed to the different cytoplasmic substrates, which ultimately leads to cell death.