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.
Mutations causing proinsulin misfolding trigger unfolded protein response and lead to impaired proliferation and reduced mTORC1 signalling of developing beta-cells in a patient-derived induced pluripotent stem cell disease model.
ER-stress sensing mechanism of the unfolded protein response sensor/transducer IRE1 is conserved from yeast to mammals, where in mammals, unfolded protein binding to IRE1's ER lumenal domain is coupled to its oligomerization and activation through an allosteric conformational change.
Death receptor 5 can directly sense misfolded proteins downstream of the endoplasmic reticulum to provide a quality control mechanism that executes apoptosis and prevents further production of misfolded proteins.
The mechanism identified here that mediates olanzapine-induced b-cell dysfunction should be considered, along with weight gain, in mitigating adverse side effects when patients with schizophrenia are prescribed olanzapine.