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Fig. 9 | Cell Communication and Signaling

Fig. 9

From: Cell death induced by the ER stressor thapsigargin involves death receptor 5, a non-autophagic function of MAP1LC3B, and distinct contributions from unfolded protein response components

Fig. 9

Schematic depiction of main conclusions. Thapsigargin (Tg) binds to and blocks SERCA (the ER Ca2+ pump), thus causing ER Ca2+ depletion and ER stress. ER stress upregulates LC3B and DR5 protein levels in a manner that requires individual contributions from ATF4 and CHOP. Tg-induced activation of caspase-8 (casp8), caspase-3 (casp3), and apoptosis is strongly dependent on DR5, and partially dependent on LC3B. PERK is required for Tg-induced caspase activation and apoptosis, but not for upregulation of LC3B- and DR5 protein levels. Thus, PERK delivers an essential pro-death signal via a different pathway. The IRE1-XBP1 axis is partially required for Tg-induced upregulation of DR5, but not LC3B. Moreover, IRE1-XBP1 is required for the second-phase activation of JNK by Tg, which contributes to caspase activation and apoptosis in a cell type-dependent manner with JNK being required for Tg-induced cell death in LNCaP but not HCT116 cells

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Cell Communication and Signaling

ISSN: 1478-811X