DAP3 binding cell death enhancer 1 (DELE1)

DAP3 binding cell death enhancer 1 (DELE1) is a mitochondrial protein that acts as a critical mediator of the integrated stress response (ISR) following mitochondrial dysfunction or iron deficiency[2][3]. It was originally identified as a DAP3-interacting protein involved in death receptor-mediated apoptosis, capable of activating caspases 3, 8, and 9 to induce cell death[1][3]. DELE1 serves as a signaling molecule that, upon mitochondrial stress, is cleaved and accumulates in the cytosol where it activates the eIF2α kinase EIF2AK1/HRI, resulting in phosphorylation of eIF2α, reduced global protein synthesis, and upregulation of ATF4[2]. In cancer, especially colorectal cancer, high levels of DELE1 correlate with poor prognosis and chemoresistance, and its knockdown enhances sensitivity to several chemotherapeutic agents[1]. Besides cancer, DELE1 has roles in mitophagy and protects against mitochondrial cardiomyopathy by mediating adaptive stress responses[3]. There are currently no drugs that specifically target DELE1 directly, but its modulation can alter the efficacy of standard chemotherapies through its effects on apoptotic and stress response pathways[1][2][3].

Other names

DELEKIAA0141DAP3-binding cell death enhancer 1Death ligand signal enhancerDELE1(L)DELE1(S)S-DELE1cDELE1

Modulation of drug sensitivity via regulation of apoptosis pathways; Mediates cell death response to mitochondrial dysfunction through caspase activation; Activates EIF2AK1/HRI leading to phosphorylation of eIF2α and ATF4 induction, triggering integrated stress response.