Ricin A chain utilises the endoplasmic reticulum-associated protein degradation pathway to enter the cytosol of yeast

Cytotoxic proteins such as ricin A chain (RTA) have target substrates in th e cytosol and therefore hale to reach this cellular compartment in order to act. RTA is thought to translocate into the cytosol from the lumen of the endoplasmic reticulum (ER), although how it traverses the ER membrane has n ot been established, Using yeast mutants defective in various aspects of th e ER-associated protein degradation (ER,ID) pathway, we shots that RTA intr oduced into the yeast ER subverts this pathway to enter the cytosol via the Sec61p translocon. A significant proportion of the exported RTA avoided pr oteasomal degradation. These data are consistent with the contention that t he RTa component from ricin endocytosed by mammalian cells may likewise exp loit ERAD to translocate into the cytosol. (C) 1999 Federation of European Biochemical Societies.