Reactome | DELE1(143-515) binds EIF2AK1 (HRI)

DELE1(143-515) binds EIF2AK1 (HRI)

Stable Identifier

R-HSA-9840429

Type

Reaction [binding]

Species

Homo sapiens

Compartment

cytosol

ReviewStatus

5/5

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The C-terminal fragment of cleaved DELE1 interacts with EIF2AK1 (HRI) in the cytosol (Fessler et al. 2020, Guo et al. 2020, Cheng et al. 2022). The interaction activates the kinase activity of EIF2AK1 (Fessler et al. 2020, Guo et al. 2020, Cheng et al. 2022) through a mechanism that may involve oligomerization of DELE1 that serves os a scaffold for EIF2AK1 binding and autophosphorylation (Yang et al. 2023). Activated EIF2AK1 then phosphorylates EIF2S1, a subunit of the EIF2alpha complex that participates in translation initiation (Fessler et al. 2020, Guo et al. 2020, Cheng et al. 2022). Phosphorylation of EIF2S1 causes a decrease in general translation and an increase in translation of specific mRNAs, such as DDIT3 (CHOP) and ATF4, that contain upstream open reading frames (Fessler et al. 2020, Guo et al. 2020, Cheng et al. 2022).

Literature References

PubMed ID	Title	Journal	Year
32132707	Mitochondrial stress is relayed to the cytosol by an OMA1-DELE1-HRI pathway Unger, BA, Tian, R, Liu, Y, Xu, K, Lin, YT, Guo, X, Kampmann, M, Correia, MA, Wiita, AP, Aviles, G	Nature	2020
32132706	A pathway coordinated by DELE1 relays mitochondrial stress to the cytosol Schmitt, S, Mancilla, IA, Fessler, E, Meyer-Bender, MF, Jae, LT, Eckl, EM, Philippou-Massier, J, Zischka, H, Krebs, S, Hanf, M	Nature	2020
35163244	The Mitochondrial PHB2/OMA1/DELE1 Pathway Cooperates with Endoplasmic Reticulum Stress to Facilitate the Response to Chemotherapeutics in Ovarian Cancer Wang, B, Kong, Q, Sun, L, Dong, D, Yu, H, Cheng, M, Shen, L	Int J Mol Sci	2022
37550454	DELE1 oligomerization promotes integrated stress response activation Chen, W, Guo, X, Yang, J, Kampmann, M, Lander, GC, Luke Wiseman, R, Baron, KR, Aviles, G, Song, AS, Schneemann, A, Pride, DE	Nat Struct Mol Biol	2023