Epithelial tumors secrete the ER-resident AGR2 in the extracellular matrix to function as a novel essential microenvironmental regulator of epithelial tissue architecture, which leads to tumorigenicity.
The small molecule, 147, is a pro-drug that preferentially activates ATF6 signaling through a mechanism involving localized metabolic activation and selective covalent modification of ER resident proteins involved in regulating ATF6 activity.
Synthetic single domain antibody libraries and a binder selection cascade encompassing ribosome and phage display enable the selection of conformation-specific binders against previously intractable membrane proteins within three weeks.
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.
Endoplasmic reticulum proteostasis factors enhance the mutational tolerance of influenza hemagglutinin, a model secretory pathway protein and therapeutic target, particularly improving the fitness of temperature-sensitive variants.