Impaired p53 Expression, Function, and Nuclear Localization in Calreticulin-deficient Cells
Bibliographic record
Abstract
The tumor suppressor protein, p53 is a transcription factor that not only activates expression of genes containing the p53 binding site but also can repress the expression of some genes lacking this binding site. Previous studies have shown that overexpression of wild-type p53 leads to apoptosis and cell cycle arrest. DNA damage, such as that caused by UV irradiation, results in p53 stabilization and nuclear localization that subsequently induces apoptosis. Recently, the level of calreticulin (CRT) has been correlated with the rate of apoptosis. Therefore, the aim of this study was to investigate the role of CRT in the regulation of apoptosis via modulating p53 function and expression. Here we show a significant decrease in both basal and DNA damage induced p53 functions in the CRT-deficient cells (crt-/-). This study is the first to demonstrate that CRT function is required for the stability and localization of the p53 protein. By using immuonocytochemical techniques, we showed that observed changes in p53 in the crt-/- cells are due to the nuclear accumulation of Mdm2 (murine double minute gene). These results, lead us to conclude that CRT regulates p53 function by affecting its rate of degradation and nuclear localization.
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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 | 0.000 | 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".