Parathyroid hormone related protein (PTHrP) inhibits TNFα‐induced apoptosis by blocking the extrinsic and intrinsic pathways
Bibliographic record
Abstract
Parathyroid hormone related protein (PTHrP) is expressed at low levels in many fetal and adult tissues where it plays a central role in regulating cell proliferation, cell death, and tissue homeostasis. In vivo and in vitro, PTHrP has been shown to promote the survival of a variety of cells by regulating expression of the anti-apoptotic protein Bcl2. Additional work has shown that intra-nuclear accumulation of PTHrP in CFK2 (PTH1R positive) and 27m21 (PTH1R negative) condrogenic cells promotes their survival by closing down ribosome biogenesis and promoting quiescence. The current studies were undertaken to examine the role of wild-type PTHrP and a mutant form that cannot translocate to the nucleus in protecting cells from TNFalpha-induced apoptosis. Both forms of the protein were equally effective in blocking the extrinsic pathway by inhibiting expression of the TNF receptor death domain, activating Bid, and promoting cleavage of caspase 8. These observations suggest a direct mechanism of PTHrP action on components of the extrinsic pathway, involving a region of the protein outside of the NTS. PTHrP and M1PTHrP also inhibited the intrinsic pathway by preventing the exchange of anti-apoptotic for pro-apoptotic proteins at the mitochondrial membrane, thus maintaining its integrity and preventing the release of caspase-activating factors into the cytosol. In general, this mitochondrial-related activity was somewhat delayed and was mediated more effectively by PTHrP than by M1PTHrP, suggesting an indirect mechanism of action that might require the presence of an intact NTS.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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 | 0.000 | 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 | 0.000 |
| 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".