DELE1

DELE; KIAA0141

Full Name

DAP3 binding cell death enhancer 1

Function

DAP3-binding cell death enhancer 1:
Key activator of the integrated stress response (ISR) following mitochondrial stress (PubMed:32132706, PubMed:32132707).

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 (PubMed:32132706, PubMed:32132707).

Essential for the induction of death receptor-mediated apoptosis through the regulation of caspase activation (PubMed:20563667).

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 (PubMed:32132706, PubMed:32132707).

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 (PubMed:32132706, PubMed:32132707).

Biological Process

Extrinsic apoptotic signaling pathway via death domain receptors Source: UniProtKB
HRI-mediated signaling Source: UniProtKB
Integrated stress response signaling Source: UniProtKB
Regulation of cysteine-type endopeptidase activity involved in apoptotic process Source: UniProtKB

Cellular Location

DAP3-binding cell death enhancer 1: Mitochondrion; Mitochondrion inner membrane. Associates with the mitochondrion inner membrane in response to mitochondrial stress, leading to its proteolytic processing by OMA1, and generation of the AP3-binding cell death enhancer 1 short form (DELE1(S) or S-DELE1).
DAP3-binding cell death enhancer 1 short form: Cytosol. This short form is generated by proteolytic processing by OMA1 in response to mitochondrial stress, leading to translocation to the cytosol.

PTM

DAP3-binding cell death enhancer 1:
Cleaved by OMA1 in response to mitochondrial stress, generating the DAP3-binding cell death enhancer 1 short form (DELE1(S) or S-DELE1) that accumulates in the cytosol and activates the protein kinase activity of EIF2AK1/HRI (PubMed:32132706, PubMed:32132707). Protein cleavage by OMA1 can take place at different positions, and apparently does not require a specific sequence motif (PubMed:32132707).