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    1. Cell Biology
    2. Neuroscience

    The small molecule ISRIB reverses the effects of eIF2α phosphorylation on translation and stress granule assembly

    Carmela Sidrauski et al.
    Building on previous work which showed that the small molecule ISRIB potently blocks the integrated stress response (Sidrauski et al., 2013), we report on ISRIB's remarkable specificity and fast action in vivo, underscoring its proposed direct effect on translation.
    1. Biochemistry and Chemical Biology
    2. Neuroscience

    eIF2B activator prevents neurological defects caused by a chronic integrated stress response

    Yao Liang Wong et al.
    Boosting the function of translation factor eIF2B by chronic small molecule administration prevents pathology in a neurodegenerative model of Vanishing White Matter disease characterized by a maladaptive stress response.
    1. Cell Biology
    2. Genetics and Genomics

    The ribosomal P-stalk couples amino acid starvation to GCN2 activation in mammalian cells

    Heather P Harding et al.
    Genetic lesions that compromise the ribosome P-stalk implicate direct signalling from the ribosome to the translation initiation factor eIF2 kinase GCN2 in the cellular response to amino acid starvation.
    1. Cell Biology
    2. Chromosomes and Gene Expression

    HRI coordinates translation necessary for protein homeostasis and mitochondrial function in erythropoiesis

    Shuping Zhang et al.
    The heme and HRI-mediated eIF2aP–ATF4 integrated stress response in erythropoiesis has a major global impact, especially under the stress condition of iron deficiency.
    1. Cancer Biology

    eIF4E S209 phosphorylation licenses myc- and stress-driven oncogenesis

    Hang Ruan et al.
    Genetic and transcriptomic analyses revealed that eIF4E S209 phosphorylation enables Myc and mutant KRAS cooperation in colon cancer through stress- and glutamine-dependent growth and addiction.
    1. Cancer Biology
    2. Cell Biology

    The mTORC1-mediated activation of ATF4 promotes protein and glutathione synthesis downstream of growth signals

    Margaret E Torrence et al.
    ATF4 is a metabolic effector of mTORC1 signaling, co-opted to induce gene targets involved in amino acid synthesis, uptake, and tRNA charging, contributing to mTORC1-driven protein and glutathione synthesis.
    1. Cell Biology
    2. Neuroscience

    Pharmacological brake-release of mRNA translation enhances cognitive memory

    Carmela Sidrauski et al.
    A compound that prevents stressors such as UV light and viral infection from downregulating protein synthesis inside cells improves memory performance in mice.
    1. Biochemistry and Chemical Biology
    2. Chromosomes and Gene Expression

    Fail-safe control of translation initiation by dissociation of eIF2α phosphorylated ternary complexes

    Martin D Jennings et al.
    Phosphorylated translation initiation factor eIF2, a potent inhibitor of protein synthesis in eukaryotic cells, is also inhibitory to protein synthesis when bound to GTP and initiator tRNA broadening the reach and immediacy of eIF2-mediated control.
    1. Microbiology and Infectious Disease

    Defining the function of OmpA in the Rcs stress response

    Kilian Dekoninck et al.
    In vivo and in vitro approaches uncover a new function for the β-barrel OmpA and reveal how it interacts with the stress sensor lipoprotein RcsF.
    1. Chromosomes and Gene Expression
    2. Neuroscience

    GTPBP1 resolves paused ribosomes to maintain neuronal homeostasis

    Markus Terrey et al.
    The translational GTPase GTPBP1 prevents ribosome stalling during tRNA deficiency and is necessary for neuronal survival.