Gene interactions and pathways from curated databases and text-mining
Cell Death Differ 2012, PMID: 21779001

mTORC1 serves ER stress-triggered apoptosis via selective activation of the IRE1-JNK pathway.

Kato, H; Nakajima, S; Saito, Y; Takahashi, S; Katoh, R; Kitamura, M

Mammalian target of rapamycin (mTOR) has a key role in the regulation of an array of cellular function. We found that rapamycin, an inhibitor of mTOR complex 1 (mTORC1), attenuated endoplasmic reticulum (ER) stress-induced apoptosis. Among three major branches of the unfolded protein response, rapamycin selectively suppressed the IRE1-JNK signaling without affecting PERK and ATF6 pathways. ER stress rapidly induced activation of mTORC1, which was responsible for induction of the IRE1-JNK pathway and apoptosis. Activation of mTORC1 reduced Akt phosphorylation, which was an event upstream of IRE-JNK signaling and consequent apoptosis. In vivo, administration with rapamycin significantly suppressed renal tubular injury and apoptosis in tunicamycin-treated mice. It was associated with enhanced phosphorylation of Akt and suppression of JNK activity in the kidney. These results disclosed that, under ER stress conditions, mTORC1 causes apoptosis through suppression of Akt and consequent induction of the IRE1-JNK pathway.

Diseases/Pathways annotated by Medline MESH: MAP Kinase Signaling System
Document information provided by NCBI PubMed

Text Mining Data

Akt ⊣ mTORC1: " Activation of mTORC1 reduced Akt phosphorylation, which was an event upstream of IRE-JNK signaling and consequent apoptosis "

Akt ⊣ mTORC1: " These results disclosed that, under ER stress conditions, mTORC1 causes apoptosis through suppression of Akt and consequent induction of the IRE1-JNK pathway "

Manually curated Databases

No curated data.