The Yeast Ubr1 Ubiquitin Ligase Participates in a Prominent Pathway That Targets Cytosolic Thermosensitive Mutants for Degradation
Bibliographic record
Abstract
Mutations causing protein misfolding and proteolysis are associated with many genetic diseases. The degradation of these aberrant proteins typically is mediated by protein-quality control pathways that recognize misfolded domains. Several E3 ubiquitin ligases have been shown to target cytosolic misfolded proteins to the proteasome. In this study, we characterized a panel of more than 20 cytosolic thermosensitive mutants from six essential genes in Saccharomyces cerevisiae. These wild-type proteins are stable at restrictive temperature. In contrast, we found that a large portion of the mutants is degraded at nonpermissive temperature in a proteasome-dependent manner. Approximately one-third of the assessed unstable mutants are targeted by the Ubr1 ubiquitin ligase. In two cases, efficient degradation of the thermosensitive mutants is abrogated in the absence of Ubr1 alone, whereas in a third case it is reliant on the dual deletion of Ubr1 and the nuclear E3 ligase San1. We found that the impairment of the degradation of these quality control substrates at the restrictive temperature is associated with the suppression of thermosensitive phenotype. This study confirms that Ubr1 plays an important role in the degradation of cytosolic misfolded proteins and indicates that degradation mediated by protein quality control is a major cause for the conditional lethality of mutated essential genes.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".