Both AKT and ERK can phosphorylate GSK 3B on the Ser9 deposit which leads to GSK 3B inactivation. Over 58 of apoptotic cells were obtained following mix treatment while using 1 uM ATO alone induced only 13% and using 5 uM sorafenib alone induced only 7% of the cells to undergo apoptosis. Since further reduction in Mcl 1 levels did not correlate with decreases in p ERK levels, other elements may possibly also donate to reduction HCV NS3 protease inhibitor in Mcl 1 levels. Inhibition of mTOR doesn’t donate to ATO induced decrease in apoptosis and Mcl 1 ranges in NB4 cells There’s accumulating evidence that Mcl 1 is translationally up regulated by mTORC1, a downstream target of PI3K/AKT. mTOR is triggered by AKT and it stimulates protein translation by phosphorylating eIF4E binding protein in addition to p70S6K which phosphorylates S6. In addition, p70S6K can be activated by ERK. The phosphorylation internet sites of p70S6K by mTOR and ERK change. While mTOR phosphorylates p70S6K at Thr389, ERK phostorylates p70S6K at Thr421/Ser424. The general levels of Posttranslational modification (PTM) phosphorylated mTOR, p70S6K, 4EBP1, and S6 were determined, if reduction of Mcl 1 levels by ATO therapy is because of the inhibition of mTOR signaling to ascertain. Consistent with a previously report we discovered that AKT levels were lowered following ATO treatment at concentration greater than 2 uM. Correlated with decreases in AKT levels, the levels of p mTOR, pp70S6K, and p 4E BP1 were also reduced after ATO therapy. It should be noticed that p70S6K levels were also reduced by ATO treatment at concentrations above 2 uM for 24 h. But, the p S6 level was lowered by ATO treatment at a concentration of only 1 uM. A period dependent study indicated that the amount of pp70S6K was reduced at 8 h treatment without reduction in Mcl 1 levels which suggests that inhibition of mTOR does not mediate the reduction of Mcl 1 levels. To study if inhibition of mTOR affected ATO induced Mcl 1 protein reduction and apoptosis, purchase Dovitinib rapamycin, an mTOR chemical, was used. Rapamycin in a concentration of 40 nM lowered p p70S6K and p S6, but not p p70S6K and Mcl 1 levels. Rapamycin did not be synergistic with ATO in reducing Mcl 1 levels in NB4 cells, even though it effectively led to reduction in p p70S6K levels. Furthermore, rapamycin pre-treatment did not improve 1 uM ATO induced apoptosis as based on annexin V analysis and both PARP cleavage. These data suggest that translational regulation by mTOR signaling isn’t the key signaling pathway by which ATO treatment results in decreased Mcl 1 protein levels. GSK 3B activation is required for apoptosis induction and Mcl 1 degradation by ATO treatment in cells Recently it has been unearthed that Mcl 1 could be phosphorylated by GSK 3B at Ser159, leading to its rapid proteasomal degradation and Mcl 1 ubiquitination.