2,509 results found
    1. Genetics and Genomics

    Distinct mitochondrial defects trigger the integrated stress response depending on the metabolic state of the cell

    Eran Mick et al.
    Mitochondrial electron transport chain dysfunction triggers the integrated stress response due to an asparagine deficiency downstream of impaired NADH oxidation in proliferating myoblasts, but not in differentiated myotubes.
    1. Biochemistry and Chemical Biology
    2. Cell Biology

    Pharmacological dimerization and activation of the exchange factor eIF2B antagonizes the integrated stress response

    Carmela Sidrauski et al.
    A drug-like molecule called ISRIB, which activates the translation initiation factor eIF2B, antagonizes stress responses as diverse as protein misfolding and nutrient deprivation, and restores protein synthesis, enhancing memory.
    1. Biochemistry and Chemical Biology
    2. Cell Biology

    Actin dynamics tune the integrated stress response by regulating eukaryotic initiation factor 2α dephosphorylation

    Joseph E Chambers et al.
    Monomeric actin forms a crucial component of the eIF2α holophosphatase linking the integrated stress response to actin polymeric status.
    1. Biochemistry and Chemical Biology
    2. Cell Biology

    eIF2B conformation and assembly state regulate the integrated stress response

    Michael Schoof et al.
    eIF2-P activates the integrated stress response by inducing a conformational change in eIF2B that decreases substrate (eIF2) binding and reduces eIF2B's catalytic activity.
    1. Biochemistry and Chemical Biology
    2. Cell Biology

    Quantitative H2S-mediated protein sulfhydration reveals metabolic reprogramming during the integrated stress response

    Xing-Huang Gao et al.
    ATF4, the master regulator of transcription during the Integrated Stress Response (ISR), causes global changes in cysteine sulfhydration of proteins and this event causes cellular metabolic reprogramming.
    1. Chromosomes and Gene Expression
    2. Computational and Systems Biology

    TASEP modelling provides a parsimonious explanation for the ability of a single uORF to derepress translation during the integrated stress response

    Dmitry E Andreev et al.
    A model reveals how translation of an mRNA leader could provide resistance to global downregulation of translation.
    1. Developmental Biology

    Inhibiting the integrated stress response pathway prevents aberrant chondrocyte differentiation thereby alleviating chondrodysplasia

    Cheng Wang et al.
    Integrated stress response-induced expression of ATF4 and its transactivation of SOX9 causes aberrant chondrocyte differentiation and skeletal defects which can be alleviated by modulating initiation-factor eIF2α phosphorylation translation control.
    1. Neuroscience

    Prolonging the integrated stress response enhances CNS remyelination in an inflammatory environment

    Yanan Chen et al.
    Oligodendrocytes with an enhanced ability to withstand cytotoxic stress display an increased capacity to remyelinate demyelination lesions of the CNS in the presence of an inflammatory environment.
    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. 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.

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