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.
By controlling the SUMOylation of the protein CAR-1, the aging-regulating pathways downstream of the Insulin/IGF signaling cascade and of the germ cells of the nematode Caenorhabditis elegans are integrated.
A whole-genome genetic screen links new aspects of oocyte maturation to proteostasis renewal in the immortal Caenorhabditis elegans germ-cell lineage and reveals similarities to somatic cell maintenance during aging.
Cells accumulate damaged proteins during aging and, by compromising the function of chaperones in folding newly synthesized G1 cyclins, proteostasis breakdown inhibits cell-cycle entry and drives yeast cells into senescence.
Cell division imposes a limit on proteostasis capacity by reducing chaperone accumulation, but chaperone-substrate interactions reverse these events to allow clearance of even chronically misfolded protein amyloids.