Atypical ubiquitylation in yeast targets lysine-less Asi2 for proteasomal degradation [Protein Synthesis and Degradation]

December 9th, 2014 by Boban, M., Ljungdahl, P. O., Foisner, R.

Proteins are typically targeted for proteasomal degradation by the attachment of a poly-ubiquitin 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 poly-ubiquitylated 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 (ERAD) pathway. Together our data suggest that non-lysine ubiquitylation may be more prevalent than currently considered.