title: 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.
authors.affiliation: From the Max F. Perutz Laboratories, Department of Medical Biochemistry, Medical University Vienna, A-1030 Vienna, Austria and.
authors.forename: Mirta
authors.initials: M
authors.lastname: Boban
authors.affiliation: the Department of Molecular Biosciences, Wenner-Gren Institute, Stockholm University SE-S-10691 Stockholm, Sweden.
authors.forename: Per O
authors.initials: PO
authors.lastname: Ljungdahl
authors.affiliation: From the Max F. Perutz Laboratories, Department of Medical Biochemistry, Medical University Vienna, A-1030 Vienna, Austria and roland.foisner@meduniwien.ac.at.
authors.forename: Roland
authors.initials: R
authors.lastname: Foisner
mesh_terms: D002467:Cell Nucleus / Q000378:metabolism; D003513:Cycloheximide / Q000737:chemistry; D004721:Endoplasmic Reticulum / Q000378:metabolism; D060746:Endoplasmic Reticulum-Associated Degradation; D000939:Epitopes / Q000737:chemistry; D015966:Gene Expression Regulation, Fungal; D008239:Lysine / Q000737:chemistry / Q000235:genetics*; D008565:Membrane Proteins / Q000378:metabolism*; D009154:Mutation; D010957:Plasmids / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D011485:Protein Binding; D012441:Saccharomyces cerevisiae / Q000201:enzymology*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*; D025801:Ubiquitin / Q000378:metabolism; D044763:Ubiquitin-Conjugating Enzymes / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism
chemical_list: C516922:Asi2 protein, S cerevisiae; D000939:Epitopes; D008565:Membrane Proteins; D029701:Saccharomyces cerevisiae Proteins; D025801:Ubiquitin; D003513:Cycloheximide; C082461:UBC6 protein, S cerevisiae; C077072:UBC7 protein, S cerevisiae; D044763:Ubiquitin-Conjugating Enzymes; C091362:SSM4 protein, S cerevisiae; D044767:Ubiquitin-Protein Ligases; D046988:Proteasome Endopeptidase Complex; D008239:Lysine
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