PI3K signaling regulates rapamycin-insensitive translation initiation complex formation in vaccinia virus-infected cells.
How vaccinia virus (VV) regulates assembly of the host translation initiation complex eIF4F remains unclear. Here, we show that VV activated host PI3K to stimulate downstream mammalian target of rapamycin (mTOR), a kinase that inactivates the translational repressor 4E-BP1. However, although the mTOR inhibitor rapamycin suppressed VV-induced inactivation of 4E-BP1, it failed to inhibit eIF4F assembly. In contrast, PI3K inhibition in VV-infected cells increased the abundance of hypophosphorylated 4E-BP1 and disrupted eIF4F complex formation. PI3K signaling, therefore, plays a critical role in regulating protein production during VV infection, at least in part by controlling the abundance and activity of 4E-BP1.
Zaborowska
Izabela
I
National Institute for Cellular Biotechnology, Dublin City University, Dublin 9, Ireland.
Walsh
Derek
D
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D018797:Cell Cycle Proteins; D002478:Cells, Cultured; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D039562:Eukaryotic Initiation Factor-4F / Q000378:metabolism; D005347:Fibroblasts / Q000821:virology; D006801:Humans; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D010750:Phosphoproteins / Q000378:metabolism; D014176:Protein Biosynthesis / Q000187:drug effects*; D020123:Sirolimus / Q000494:pharmacology*; D014616:Vaccinia virus / Q000502:physiology*
D048868:Adaptor Proteins, Signal Transducing; D018797:Cell Cycle Proteins; D004791:Enzyme Inhibitors; D039562:Eukaryotic Initiation Factor-4F; D019869:Phosphatidylinositol 3-Kinases; D010750:Phosphoproteins; D020123:Sirolimus; C087000:EIF4EBP1 protein, human