O-mannosylation of misfolded ER proteins promotes ERAD.

ABSTRACT: Protein quality control (PQC) in the secretory pathway, a process critically linked to numerous human diseases, begins in the endoplasmic reticulum (ER) and involves ER-associated degradation (ERAD) of terminally misfolded proteins. In this study, we conducted genome-wide screens in baker's yeast (Saccharomyces cerevisiae) to investigate the degradation of Gas1*, a misfolded version of an O-mannosylated, glycosylphosphatidylinositol (GPI)-anchored protein. In combination with detailed biochemical and genetic analyses, these screens revealed an unexpected bifunctionality of the evolutionarily conserved heteromeric enzyme complex Pbn1-Gpi14: while it has been previously recognized as a GPI-mannosyltransferase, we here find that it catalyzes the O-mannosylation of misfolded proteins, thereby

SUBMITTER: Lemus L 

PROVIDER: S-EPMC12811338 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature