knockdown of S6K2 had little impact on boosting TNF induced cell death when Bid was depleted by siRNA silencing. TNF is HCV Protease Inhibitors demonstrated to stimulate mTOR signaling and we have found that TNF preferentially activates S6K1, presumably since the abundance of S6K1 is significantly larger in comparison with S6K2 in MCF 7 cells. We made a novel observation that in contrast to S6K1, S6K2 positively handles Akt. Knock-down of S6K2 caused a decrease in both basal and TNF induced Akt phosphorylation, which can be indicative of its activation status, suggesting that S6K2 promotes cell survival via activation of Akt. The truth is, over-expression of CA Akt blocked escalation in cell death brought on by S6K2 exhaustion, indicating that S6K2 acts upstream of Akt although we cannot exclude the possibility that Akt andS6K2 act in parallel pathways where Akt includes a dominant role over S6K2. There are numerous potential mechanisms through which S6K2 influences phosphorylation/activity of Akt. Since mTORC2 activates Akt by phosphorylating in the hydrophobic site, it is likely that knockdown of S6K2 reduces Akt phosphorylation by inhibiting mTORC2. The others and we have also shown that Ser473 phosphorylation of Akt is also controlled Cellular differentiation by DNA dependent protein kinase. Another possibility is that S6K2 knock-down increases PTEN level leading to inhibition of Akt, because PTEN prevents PI3K/Akt. It’s been reported a significant kinase downstream of mTORC2 is SGK1. Thus, it’s also important to decide if S6K2 regulates cell survival via SGK1. Furthermore, since activation of Akt would result in the activation of mTORC1, there could be a positive feedback loop between Akt and S6K2. Thus, mTORC1 and its downstream targets might mediate some of the consequences of the potential functional connection between S6K2 and Akt. Future studies should discern the mechanisms by which S6K2 regulate Akt and the functional relationship BAY 11-7821 between Akt and S6K2. Our declare that the mechanism where S6K2 promotes cell survival via Akt requires the proapoptotic Bcl 2 family protein Bid. We have previously found that activation of Akt may cause a decrease in p53 levels in MCF 7 cells by phosphorylating and stabilizing Hdm2, which degrades p53 via the ubiquitin proteasome mediated process. We’ve also found that Bid is a transcriptional target of p53 and Akt may reduce Bid expression by inducing down-regulation of p53. The of our present study show that knockdown of S6K2 improved p53 and silencing of p53 was connected with a decrease in Bid. But, exhaustion of S6K2 wasn’t related to upregulation of Bid. We’ve previously shown that overexpression of Bid is enough to cause cell death. Since Bid is a proapoptotic protein, a growth in Bid may also result in its cleavage. For that reason, it could be difficult to show an increase in Bid stage. Moreover, knock-down of S6K2 failed to enhance cell death in MDA MB 231 cells, which express mutant p53.