Posttranscriptional regulation of the p85α.alpha; adapter subunit of phosphatidylinositol 3-kinase in human leukemia cells

Abstract

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 (p110α, p110β, p110δ) and an adapter subunit (p85α, p55α, p50α, p85β, p55γ). The p85α adapter subunit stabilizes the catalytic p110 subunit and recruits p110 to the plasma membrane. In addition, p85α inhibits the basal activity of p110α and can negatively regulate signal transduction, as shown for insulin and GM-CSF receptor signaling. Here, we describe that the expression of p85α 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 p85α mRNA are detectable at similar ratios in the nucleus and polysomes. However, while the mutated p85α protein is expressed in CO cells, translation of the wild type p85α mRNA is completely inhibited. Ectopic expression of wild type p85α 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 p85α by posttranscriptional regulation.

Keywords:

• Phosphatidylinositol 3-kinase
• p85α
• leukemia
• posttranscriptional regulation

Acknowledgements

The excellent technical assistance of W. Wegner and A. Düsedau is gratefully acknowledged. We would like to thank R. A. Feldman for the retroviral vector MIGR I, G. Nolan for the Phoenix cell line, B. Fehse for the PG13 cell line, H. Tesch for the CO cell line, A. Guse for the Jurkat cell line, C. Stocking for the Kasumi and HT1080 cell lines, J. Duyster for the MV4-11 and EOL-1 cell lines, J. Friel for the K562 cell line, G. Schuch for the M1 cell line, and A. Grundhoff for his help with the miRNA database search.

Declaration of interest:The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.