TGFβ mediates activation of transglutaminase 2 in response to oxidative stress that leads to protein aggregation
Bibliographic record
Abstract
ABSTRACT Transglutaminase 2 (TGase2) is a ubiquitously expressed enzyme that catalyzes irreversible post‐translational modification of protein, forming cross‐linked protein aggregates. We previously reported that intracellular TGase2 is activated by oxidative stress. To elucidate the functional role of TGase2 activation in cells under the oxidatively stressed condition, we identified the mediator that activates TGase2. In this study, we showed that low levels of oxidative stress trigger the release of TGF β , which subsequently activates TGase2 through the nuclear translocation of Smad3. Analysis of substrate proteins reveals that TGase2‐mediated protein modification results in a decrease of protein solubility and a collapse of intermediate filament network, which leads to aggregation of proteins. We confirm these results using lens tissues from TGase2‐deficient mice. Among several antioxidants tried, only N ‐acetylcysteine effectively inhibits TGF β ‐mediated activation of TGase2. These results indicate that TGF β mediates oxidative stress‐induced protein aggregation through activation of TGase2 and suggest that the formation of protein aggregation may not be a passive process of self‐assembly of oxidatively damaged proteins but may be an active cellular response to oxidative stress. Therefore, TGFP‐TGase2 pathway may have implications for both the pathogenesis of age‐related degenerative diseases and the development of pharmaceutics.—Shin, D.‐M., Jeon, J.‐H., Kim, C.‐W., Cho, S.‐Y., Lee, H.‐J., Jang, G.‐Y., Jeong, E. M., Lee, D.‐S., Kang, J.‐H., Melino, G., Park, S.‐C., Kim, I.‐G. TGFβ mediates activation of transglutaminase 2 in response to oxidative stress that leads to protein aggregation. FASEB J. 22, 2498–2507 (2008)
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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".