Fig. 3
From: Unfolded protein response (UPR) integrated signaling networks determine cell fate during hypoxia
Hypoxia signaling and the related changes in cellular functions activate the UPR and UPRmt. During hypoxia, accumulation of misfolded/unfolded proteins in ER and mitochondria activate PERK signaling, and this contributes to both pro-survival (global translational arrest and induction of pro-angiogenic genes IL8 and VEGF) and apoptotic responses (induction of CHOP and inhibition of pro-angiogenic eNOS expression). Furthermore, in some models, hypoxia-related activation of ATF6 and IRE1α contributes to pro-survival and pro-angiogenic signaling. There also appears to be cooperation between XBP1s and HIF1 in pro-survival signaling