Heat‐induced degrons and the co‐chaperone Ydj1‐adaptor mediate the ubiquitination of misfolded proteins by the Rsp5 ubiquitin ligase upon stress (558.1)
Bibliographic record
Abstract
The ubiquitin proteasome system is critical for the prompt elimination of misfolded proteins, which pose a deleterious risk to the cell. Indeed numerous diseases are associated with protein misfolding and aggregation. The heat‐shock response mediates several cellular events to prevent accumulation of misfolded proteins including upregulation of heat‐shock proteins and increased proteolysis. We found that upon heat‐stress Rsp5 is the main E3 ligase that ubiquitinates cytosolic misfolded proteins to target them for proteasome degradation. Notably, degradation of misfolded proteins is dependent on both Ubp2 and Ubp3 deubiquitinases. The absence of either deubiquitinase leads to reduced cell fitness upon misfolding stresses. We also found that the association of Rsp5 with the Hsp40 co‐chaperone Ydj1 increases upon stress and that association is required for the ubiquitination of heat‐induced Rsp5 substrates. In addition, PY Rsp5‐binding motifs are also enriched among heat‐induced Rsp5 substrates and found primarily in structured regions, often less accessible. Our results support a bipartite recognition mechanism combining chaperone‐dependent and heat‐induced degrons that mediate ubiquitination of cytosolic misfolded proteins by Rsp5.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 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 | 0.001 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.002 | 0.001 |
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 source (direct Gemma or distilled Codex), 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".