ERp57 Modulates STAT3 Signaling from the Lumen of the Endoplasmic Reticulum
Bibliographic record
Abstract
ERp57 is an endoplasmic reticulum (ER) resident thiol disulfide oxidoreductase. Using the gene trap technique, we created a ERp57-deficient mouse model. Targeted deletion of the Pdia3 gene, which encodes ERp57, in mice is embryonic lethal at embryonic day (E) 13.5. Beta-galactosidase reporter gene analysis revealed that ERp57 is expressed early on during blastocyst formation with the highest expression in the inner cell mass. In early stages of mouse embryonic development (E11.5) there is a relatively low level of expression of ERp57. As the embryos developed, ERp57 became highly expressed in both the brain and the lungs (E15.5 and E18.5). The absence of ERp57 has no impact on ER morphology; expression of ER-associated chaperones and folding enzymes, ER stress, or apoptosis. ERp57 has been reported to interact with STAT3 (signal transducer and activator of transcription)-DNA complexes. We show here that STAT3-dependent signaling is increased in the absence of ERp57 and this can be rescued by expression of ER-targeted ERp57 but not by cytoplasmic-targeted protein, indicating that ERp57 affects STAT3 signaling from the lumen of the ER. ERp57 effects on STAT3 signaling are enhanced by ER luminal complex formation between ERp57 and calreticulin. In conclusion, we show that ERp57 deficiency in mouse is embryonic lethal at E13.5 and ERp57-dependent modulation of STAT3 signaling may contribute to this phenotype.
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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) | 0.000 | 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 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 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 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".