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. Author manuscript; available in PMC: 2017 Aug 19.
Published in final edited form as: ACS Chem Biol. 2016 Jun 9;11(8):2195–2205. doi: 10.1021/acschembio.5b00940

Figure 1. Divergent Modulation of IRE1α RNase activity.

Figure 1

(A) Model of IRE1α activation under ER stress. IRE1α contains a stress sensing lumenal domain linked to a cytosolic kinase and RNase domain by a transmembrane linker. In the presence of unfolded proteins in the ER, IRE1α is activated to initiate an adaptive response. Prolonged ER stress leads to IRE1α oligomerization and endonucleolytic decay of ER-localized mRNAs (B) Allosteric inhibition of IRE1α’s RNase activity with an ATP-competitive inhibitor–KIRA6–under ER stress. (C) Allosteric activation of IRE1α’s RNase activity with an ATP-competitive inhibitor–APY29–in the absence of ER stress.