A novel hypoxia-inducible factor-independent hypoxic response regulating mammalian target of rapamycin and its targets.

摘要: Hypoxia triggers a reversible inhibition of protein synthesis thought to be important for energy conservation in O2-deficient environments. The mammalian target rapamycin (mTOR) pathway integrates multiple environmental cues regulate translation response nutrient availability and stress, suggesting it as candidate O2 regulation. We show here that hypoxia rapidly reversibly hypophosphorylation mTOR its effectors 4E-BP1, p70S6K, rpS6, eukaryotic initiation factor 4G. Hypoxic regulation these translational control proteins is dominant activation via distinct signaling pathways such insulin, amino acids, phorbol esters, serum independent Akt/protein kinase B AMP-activated phosphorylation, ATP levels, ATP:ADP ratios, hypoxia-inducible factor-1 (HIF-1). Finally, appears repress phosphorylation manner analogous phosphatase 2A (PP2A) activity. These data demonstrate new mode the position this powerful point by cellular metabolism energetics.