Translational Repression Mediates Activation of Nuclear Factor Kappa B by Phosphorylated Translation Initiation Factor 2

• DOI: 10.1128/mcb.24.23.10161-10168.2004
• Publication Date: 2004-11-12T23:37:59Z
• Authors: Jing Deng; Phoebe D. Lu; Yuhong Zhang; Donalyn Scheuner; Randal J. Kaufman; Nahum Sonenberg; Heather P. Harding; David Ron
• Keywords: eIF2; Phosphorylation cascade; EIF4EBP1; Eukaryotic initiation factor; Translational regulation

Numerous stressful conditions activate kinases that phosphorylate the alpha subunit of translation initiation factor 2 (eIF2α), thus attenuating mRNA and activating a gene expression program known as integrated stress response. It has been noted associated with eIF2α phosphorylation, notably accumulation unfolded proteins in endoplasmic reticulum (ER), or ER stress, are also activation nuclear kappa B (NF-κB) phosphorylation is required for NF-κB by stress. We have used pharmacologically activable version pancreatic kinase (PERK, an stress-responsive kinase) to uncouple from found both necessary sufficient DNA binding reporter gene. phosphorylation-dependent correlated decreased levels inhibitor IκBα protein. Unlike canonical signaling pathways promote degradation, did not increase phosphorylated affect stability Pulse-chase labeling experiments indicate instead repression plays important role cells experiencing high phosphorylation. These studies suggest direct translational control during