Prevention of p53 Degradation in Human MCF‐7 Cells by Proteasome Inhibitors Does Not Mimic the Action of Roscovitine
Bibliographic record
Abstract
We have recently observed activation of wild-type (wt) p53 protein in human MCF-7 breast cancer cells upon treatment with roscovitine (ROSC), a potent cyclin-dependent kinase inhibitor. It has been previously suggested that ROSC repressed transcription of Mdm-2, a negative p53 regulator, and that the lack of Mdm-2 contributes to the ROSC-induced upregulation of p53 protein. Therefore, we decided to see whether the prevention of p53 degradation by proteasome inhibitors will mimic the effects generated by ROSC. Exposure of human MCF-7 cells to different proteasome inhibitors resulted in a time-dependent increase of p53. However, unlike ROSC, they failed to modify p53 protein at Ser46 and to induce p53AIP1 protein. Moreover, whereas ROSC arrested MCF-7 cells in the G2-phase of the cell cycle, proteasome inhibitors blocked cells primarily in the S-phase, presumably because of the prevention of cyclin degradation. Our results indicate that prevention of p53 degradation by proteasome inhibitors does not mimic the action of ROSC.
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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 | 0.001 |
| Science and technology studies | 0.000 | 0.001 |
| 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".