DAP3-binding cell death enhancer 1

Definition:

[DAP3-binding cell death enhancer 1]: Key activator of the integrated stress response (ISR) following mitochondrial stress. In response to mitochondrial stress, cleaved by the protease OMA1, generating the DAP3-binding cell death enhancer 1 short form (DELE1(S) or S-DELE1), which translocates to the cytosol and activates EIF2AK1/HRI to trigger the ISR. Essential for the induction of death receptor-mediated apoptosis through the regulation of caspase activation.; [DAP3-binding cell death enhancer 1 short form]: Protein kinase activator generated by protein cleavage in response to mitochondrial stress, which accumulates in the cytosol and specifically binds to and activates the protein kinase activity of EIF2AK1/HRI. It thereby activates the integrated stress response (ISR): EIF2AK1/HRI activation promotes eIF-2-alpha (EIF2S1) phosphorylation, leading to a decrease in global protein synthesis and the induction of selected genes, including the transcription factor ATF4, the master transcriptional regulator of the ISR.

References:

[1]. Xiaoyan Guo, et al. Mitochondrial stress is relayed to the cytosol by an OMA1-DELE1-HRI pathway. Nature. 2020 Mar;579(7799):427-432. [Content Brief]

[2]. Evelyn Fessler, et al. A pathway coordinated by DELE1 relays mitochondrial stress to the cytosol. Nature. 2020 Mar;579(7799):433-437. [Content Brief]

[3]. Tanenobu Harada, et al. Identification of DELE, a novel DAP3-binding protein which is crucial for death receptor-mediated apoptosis induction. Apoptosis. 2010 Oct;15(10):1247-55. [Content Brief]

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