Fig. 4.
The IFN-α-induced HIF-1α expression is mediated through downstream PI3K/AKT/mTOR/GSK3β pathway. a Both the activation of AKTS473 and HIF-1α expression induced by IFN-α were blocked by co-treatment of PI3K (LY, 10 μM) or mTOR inhibitors (Rapa 0.1 μM). Quantitation data is shown in the right. b-e The IFN-α-induced HIF-1α expression is PI3K/AKT/mTOR-dependent. HIF-α expression is abrogated in si-AKT and si-mTOR knockdown cells (b), by exposure to AKT inhibitor iv (AKTi, c), in the AKT-DN- (d) and PTEN-expressing cells (e). f IFN-α treatment activates time-dependent GSK3βS9 phosphorylation and degradation. g Phosphorylation of GSK3βS9 is involved in the IFN-α induced HIF-1α expression. Inhibitors were pretreated 30 min before exposure to IFN-α and subsequently corresponding experiments were carried out as described in “Methods”. Transient plasmid transfections were performed as described 24-h before treatments. *, P < 0.05; N.S., non- significant