Zattas D, et al. (2013) N-terminal acetylation of the yeast Derlin Der1 is essential for Hrd1 ubiquitin-ligase activity toward luminal ER substrates. Mol Biol Cell 24(7):890-900
Abstract: Two conserved ubiquitin ligases, Hrd1 and Doa10, mediate most endoplasmic reticulum-associated protein degradation (ERAD) in yeast. Degradation signals (degrons) recognized by these ubiquitin ligases remain poorly characterized. Doa10 recognizes the Deg1 degron from the MATalpha2 transcription factor. We previously found that deletion of the gene (NAT3) encoding the catalytic subunit of the NatB N-terminal acetyltransferase weakly stabilized a Deg1-fusion protein. By contrast, a recent analysis of several MATalpha2 derivatives suggested that N-terminal acetylation of these proteins by NatB was crucial for recognition by Doa10. We now analyze endogenous MATalpha2 degradation in cells lacking NatB and observe minimal perturbation relative to wild-type cells. However, NatB mutation strongly impairs degradation of ER-luminal Hrd1 substrates. This unexpected defect derives from a failure of Der1, a Hrd1 complex subunit, to be N-terminally acetylated in NatB mutant yeast. We retargeted Der1 to another acetyltransferase to show that it is the only ERAD factor requiring N-terminal acetylation. Preventing Der1 acetylation stimulates its proteolysis via the Hrd1 pathway, at least partially accounting for the ERAD defect observed in the absence of NatB. These results reveal an important role for N-terminal acetylation in controlling Hrd1 ligase activity toward a specific class of ERAD substrates.
|Status: Published||Type: Journal Article | Research Support, N.I.H., Extramural||PubMed ID: 23363603|
Topics addressed in this paper
Number of different genes curated to this paper: 9
- To go to the Locus page for a gene, click on the gene name.