2,010 results found
    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. 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

    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. 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. Cancer Biology

    MARCH5 mediates NOXA-dependent MCL1 degradation driven by kinase inhibitors and integrated stress response activation

    Seiji Arai et al.
    MARCH5 mediates a pathway driving MCL1 degradation in response to cellular stress, which sensitizes to BH3 mimetic drugs targeting BCLXL and provides a broadly effective therapeutic strategy for solid tumors.
    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. 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. 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. 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.

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