Posttranscriptional regulation of the p85αα.alpha; adapter subunit of phosphatidylinositol 3-kinase in human leukemia cells

Constitutive activation of phosphatidylinositol 3-kinase ((PI3K))//Akt signaling has been observed in up to 70%% of acute myeloid leukemia. Class I-A PI3K consists of a catalytic subunit ((p110 alpha alpha, p110 beta beta, p110 delta delta)) and an adapter subunit ((p85 alpha alpha, p55 alpha alpha, p50 alpha alpha, p85 beta beta, p55 gamma gamma)). The p85 alpha alpha adapter subunit stabilizes the catalytic p110 subunit and recruits p110 to the plasma membrane. In addition, p85 alpha alpha inhibits the basal activity of p110 alpha alpha and can negatively regulate signal transduction, as shown for insulin and GM-CSF receptor signaling. Here, we describe that the expression of p85 alpha alpha is posttranscriptionally regulated in several human and murine leukemia cell lines and in a Hodgkin lymphoma cell line ((CO)) by translational repression. A detailed analysis of CO cells revealed that both wild type and a mutated p85 alpha alpha mRNA are detectable at similar ratios in the nucleus and polysomes. However, while the mutated p85 alpha alpha protein is expressed in CO cells, translation of the wild type p85 alpha alpha mRNA is completely inhibited. Ectopic expression of wild type p85 alpha alpha from a retroviral vector is suppressed in CO cells and in five out of six leukemia cell lines. Our data indicate that leukemia cells can regulate the expression of p85 alpha alpha by posttranscriptional regulation.</.