Unfolded Protein Response (UPR): Cellular control for our errors in life
Bibliographic record
Abstract
The unfolding protein response (UPR) is critical for the maintenance of cellular function under endoplasmic reticulum (ER) stress. Under stress conditions, proteins in the ER may misfold and accumulate into aggregates. To prevent aggregate accumulation, BiP is released from ATF6, IRE1 or PERK to bind to the misfolded proteins and assist in ATP mediated chaperone refolding. With the loss of BiP, ATF6 travels to the Golgi and is cleaved to a nucleus targeting form that promotes expression of UPR-responsive genes. IRE1 homodimerizes upon release of BiP to form an active RNase domain that removes an intron sequence from the XBP1 mRNA transcript. XBP1 is another promoter protein that is also responsible for UPR gene transcription. PERK homodimerizes upon BiP release and forms an active kinase domain that attenuates general translation and increases translation of specific UPR transcripts. Under prolonged UPR stimulation, IRE1 signals for proteins responsible for ER associated degradation. These proteins remove the misfolded proteins from the ER and bring them to the proteasome for degradation. If the misfolded proteins are not refolded or cleared from the ER, then the cell may be targeted for apoptosis. False UPR signals or accumulation of mutant or misfolded proteins in the ER lead to many diseases. Understanding the UPR pathway and signals that are involved may offer a template for designing novel therapeutics to help alleviate the symptoms of misfolding diseases or assist in refolding these proteins.
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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) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.002 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.004 | 0.003 |
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".