Atypical ubiquitylation in yeast targets lysine-less Asi2 for proteasomal degradation

Abstract

Proteins are typically targeted for proteasomal degradation by the attachment of a polyubiquitin chain to ϵ-amino groups of lysine residues. Non-lysine ubiquitylation of proteasomal substrates has been considered an atypical and rare event limited to complex eukaryotes. Here we report that a fully functional lysine-less mutant of an inner nuclear membrane protein in yeast, Asi2, is polyubiquitylated and targeted for proteasomal degradation. Efficient degradation of lysine-free Asi2 requires E3-ligase Doa10 and E2 enzymes Ubc6 and Ubc7, components of the endoplasmic reticulum-associated degradation pathway. Together, our data suggest that non-lysine ubiquitylation may be more prevalent than currently considered.

Keywords: E2 Ubiquitin-conjugating Enzymes (Ubc6, Ubc7); E3 Ubiquitin Ligase (Doa10); Endoplasmic Reticulum-associated Protein Degradation (ERAD); Inner Nuclear Membrane; Nuclear Envelope; Polytopic Membrane Proteins; Proteasome; Protein Degradation; Saccharomyces cerevisiae; Ubiquitin.