Abstract 3504: Arginylated BiP/oxidized DJ-1 complex mediates crosstalk between the endoplasmic reticulum and mitochondria

Abstract

Abstract In cell death induced by tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), although much is known about signal pathways involving external signals through cell surface receptors or internal signals through mitochondrial dysfunction, little is known about signal pathways activated by endoplasmic reticulum (ER) stress during TRAIL treatment. Here, we report that TRAIL-induced caspase activation is a prerequisite for TRAIL-induced ER stress response. During TRAIL treatment, ER chaperon BiP dissociates from ER stress sensors such as PERK and IRE1α and the activation of the PERK-eIF2α-ATF4-CHOP apoptotic signal transduction pathway occurs. Meanwhile ER-stress induces BiP release to the cytosol and ATE1-encoded Arg-tRNA transferase arginylates BiP. TRAIL also induces loss of ΔΨm and redox sensor DJ-1 detects mitochondria-derived ROS. Oxidized DJ-1 binds to arginylated BiP (R-BiP) in the cytosol. DJ-1 binding activity was abrogated in C106A and C53A but not C46A mutant. R-BiP/oxidized DJ-1 complex may mediate crosstalk between the ER and mitochondria. Key words: TRAIL; endoplasmic reticulum; apoptosis; colorectal cancer Citation Format: Dae-Hee Lee. Arginylated BiP/oxidized DJ-1 complex mediates crosstalk between the endoplasmic reticulum and mitochondria. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3504.