In response to proteotoxic stress, squamous cell carcinoma cells hijack the integrated stress response to promote recovery by bolstering protection of microtubule dynamics.
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.
Ernie Yulyaningsih, Jung H Suh ... Pascal E Sanchez
DNL343, a brain-penetrant integrated stress response inhibitor, reduces neurodegeneration in mouse models and identifies biomarker candidates for assessing treatment responses in clinical settings.
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.
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.
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.
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.