Loss of transcriptional regulator of phospholipid biosynthesis alters post-translational modification of Sec61 translocon beta subunit Sbh1 in .

We recently discovered that disrupting phospholipid biosynthesis by eliminating the Ino2/4 transcriptional regulator impairs endoplasmic reticulum (ER)-associated degradation (ERAD) in , but the mechanism is unclear. Phosphatidylcholine deficiency has been reported to accelerate degradation of Sec61 translocon beta subunit Sbh1 and ERAD cofactor Cue1. Here, we found that, unlike targeted phosphatidylcholine depletion, deletion does not destabilize Sbh1 or Cue1.

Lipid biosynthesis perturbation impairs endoplasmic reticulum-associated degradation.

The relationship between lipid homeostasis and protein homeostasis (proteostasis) is complex and remains incompletely understood. We conducted a screen for genes required for efficient degradation of Deg1-Sec62, a model aberrant translocon-associated substrate of the endoplasmic reticulum (ER) ubiquitin ligase Hrd1, in Saccharomyces cerevisiae. This screen revealed that INO4 is required for efficient Deg1-Sec62 degradation.

APC/C and Slx5p/Slx8p ubiquitin ligases confer resistance to aminoglycoside hygromycin B in .

Multiple ubiquitin ligases with nuclear substrates promote regulated protein degradation and turnover of protein quality control (PQC) substrates. We hypothesized that two ubiquitin ligases with nuclear substrates – the anaphase-promoting complex/cyclosome with the Cdh1p substrate recognition factor (APC/C ) and the Slx5p/Slx8p SUMO-targeted ubiquitin ligase – contribute to PQC. We predicted yeast lacking subunits of these enzymes would exhibit compromised growth in the presence of hygromycin B, which reduces translational fidelity.