title: Posttranscriptional regulation of the p85α 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.
authors.affiliation: Center of Experimental Medicine, Institute of Biochemistry and Molecular Biology I, Cellular Signal Transduction, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Bianca T
authors.initials: BT
authors.lastname: Hofmann
authors.forename: Elion
authors.initials: E
authors.lastname: Hoxha
authors.forename: Evita
authors.initials: E
authors.lastname: Mohr
authors.forename: Katrin
authors.initials: K
authors.lastname: Schulz
authors.forename: Manfred
authors.initials: M
authors.lastname: Jücker
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D058543:Class Ia Phosphatidylinositol 3-Kinase / Q000235:genetics* / Q000378:metabolism*; D015973:Gene Expression Regulation, Leukemic; D006801:Humans; D019169:Jurkat Cells; D020014:K562 Cells; D007938:Leukemia / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D050505:Mutant Proteins / Q000235:genetics / Q000378:metabolism; D041681:NIH 3T3 Cells; D011132:Polyribosomes / Q000378:metabolism; D034622:RNA Interference / Q000502:physiology; D012323:RNA Processing, Post-Transcriptional / Q000502:physiology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
chemical_list: D050505:Mutant Proteins; D012333:RNA, Messenger; D058543:Class Ia Phosphatidylinositol 3-Kinase