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. Author manuscript; available in PMC: 2011 Aug 9.
Published in final edited form as: Mol Cell. 2006 Feb 17;21(4):521–531. doi: 10.1016/j.molcel.2006.01.010

Figure 7. Schematic diagram for the signaling pathways modulated by low O2 that lead to translational inhibition.

Figure 7

Hypoxia suppresses signaling for translation initiation, elongation, and ribosome biogenesis via concomitant inhibition of eIF2α eEF2, and mTOR downstream targets 4EBP1, p70S6K, and rpS6. The mTOR regulation involves the AMPK/TSC2/Rheb pathway and is activated by hypoxia-induced decreases in cellular bioenergetics. The eIF2α phosphorylation may be trigged by ER-stress activated PERK and the eEF2 inhibition involves AMPK. HIF-inducible REDD1 has been implicated in the regulation of mTOR upstream of TSC2. Mutations of TSC2 in tumor cells greatly impede hypoxia-induced mTOR inhibition and G1 arrest. Thus, hypoxic translational control may ultimately affect cell growth and proliferation under low O2.