Coping with stress: eIF2 kinases and translational control

摘要: In response to environmental stresses, a family of protein kinases phosphorylate eIF2 (eukaryotic initiation factor 2) alleviate cellular injury or alternatively induce apoptosis. Phosphorylation reduces global translation, allowing cells conserve resources and initiate reconfiguration gene expression effectively manage stress conditions. Accompanying this general synthesis control, phosphorylation induces translation specific mRNAs, such as that encoding the bZIP (basic leucine zipper) transcriptional regulator ATF4 (activating transcription 4). also enhances additional factors, ATF3 CHOP (CCAAT/enhancer-binding homologous protein)/GADD153 (growth arrest DNA-damage-inducible protein), assist in regulation genes involved metabolism, redox status Reduced by can lead activation stress-related NF-kappaB (nuclear kappaB), lowering steady-state levels short-lived regulatory proteins IkappaB (inhibitor NF-kappaB). While many induced are shared between different function conjunction with other stress-response pathways, those regulated mitogen-activated kinases, elicit programmes tailored for condition. Loss kinase pathways have important health consequences. Mice devoid GCN2 [general control non-derepressible-2 EIF2AK4 (eIF2alpha 4)] show sensitivity nutritional deficiencies aberrant eating behaviours, deletion PEK [pancreatic eIF2alpha PERK (RNA-dependent kinase-like endoplasmic reticulum kinase) EIF2AK3] leads neonatal insulin-dependent diabetes, epiphyseal dysplasia hepatic renal complications.