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eIF 2α kinases PERK and GCN 2 act on FOXO to potentiate FOXO activity
Author(s) -
You Shiqiu,
Li Huifang,
Hu Zhubing,
Zhang Wei
Publication year - 2018
Publication title -
genes to cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.912
H-Index - 115
eISSN - 1365-2443
pISSN - 1356-9597
DOI - 10.1111/gtc.12625
Subject(s) - biology , kinase , phosphorylation , function (biology) , microbiology and biotechnology , phenotype , gene , genetics
Abstract PERK and GCN 2 are eIF 2α kinases known to mediate the effects of ER stress and respond to an array of diverse stress stimuli. Previously, we reported that ER stress potentiates insulin resistance through PERK ‐mediated FOXO phosphorylation. Inhibition of PERK improves cellular insulin responsiveness at the level of FOXO activity. Here we provide further evidence that FOXO is required for the functional output of PERK by showing that lowering FOXO activity ameliorates a PERK gain‐of‐function phenotype in Drosophila . More importantly, we present results demonstrating that GCN 2 acts similarly to PERK to promote FOXO activity. Regulation of FOXO by GCN 2 is evolutionarily conserved and can be compensated for by PERK . The combination of these mechanisms may contribute to the complex regulatory network between PERK , GCN 2, and FOXO , which has been implicated in the development and progression of a variety of diseases.