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Survivin which is belonged to Inhibitor of Apoptosis Proteins (IAPs) family, is well reported to protect cell from apoptotis by inhibiting caspases pathway. But until present time, to our knowledge, it is not reported yet whether survivin could protect cell from apoptosis by inducing survival signal. In our study, we found that survivin could bind and induce PKA activity. PKA is an important second messenger in cell signaling, which can induce various pathways, including PI3K. In our study, it is shown that survivin could induce PI3K activity and convert PI(4,5)P2 to PI(3,4,5)P3 through PKA. Then PI(3,4,5)P3 will attract many proteins to cell membrane like PDK and Akt. Akt, when it is activated, it will phosphorylate its downstream signals such as Bad, Forkhead family and IKKs to promote cell survival. In our study, it is shown also that survivin stimulated-PI3K could induce Akt phosphorylation and activity. The signal was later continued to Bad and IKKb, which were phosphorylated and activated, so that TRAIL-stimulated and IL-3-deprived apoptosis could be inhibited. |
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