Investigating the Role of p53 in Cellular Stress Responses to Deregulated Anabolic Metabolism
Bibliographic record
Abstract
Pharmacology-based cancer risk reduction has emerged as a promising potential complement to existing cancer screening strategies employed in LFS and other CPSs. At a basic, physiological level, cancer prevention effects have been associated most closely with anabolic metabolism and mTORC1. Unfortunately, strategies involving direct inhibition of mTORC1 are clinically undesirable, necessitating further investigation of the molecular mechanisms underlying cancer risk reduction – the correlates of malignancy in LFS. In this work, we provide evidence for a molecular circuitry which may maintain growth homeostasis in the pre-malignant niche. Through pharmacological perturbation of growth rate and cell cycle length, we observed that wild-type p53 and p38 provoke opposite, complementary stress responses to relatively hyperactivated and diminished biosynthesis, respectively. More specifically, p53 inhibits mTORC1 and p38 to curtail further biosynthesis when it is already elevated. The p53 GOF mutant R248Q appears to break this homeostasis, which may contribute to unchecked anabolism and tumour development.
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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) | 0.002 | 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".