Over‐expression of <scp>ATR</scp> causes autophagic cell death
Bibliographic record
Abstract
ATR is highly conserved in all eukaryotes and functions as a cell‐cycle checkpoint kinase to stabilize the nuclear genome. In addition, knockout mouse models indicate that ATR is essential for viability. Here, it is shown that moderate overproduction of ATR , but not of the other phosphatidylinositol 3′ kinase‐related kinases, ataxia‐telangiectasia‐mutated, m TOR and SMG ‐1, and a downstream target p53, resulted in cell death. ATR over‐expression induced cellular vacuolization from 12 to 48 h after transfection, before cell death progression. A series of deletion analyses showed that overproduction of the N ‐terminal HEAT repeat segments of ATR was sufficient for the induction of the vacuolization. Moreover, post‐transcriptional modification of LC 3, a marker of autophagy, and autophagosomes with double membranes were evident in ATR ‐overproducing cells. The vacuolization was also suppressed in autophagy‐deficient MCF 7 cells. In addition, both cellular vacuolization and cell death were reduced by inhibition of R as activity using farnesyl thiosalicylic acid. Conversely, neither inhibition of m TOR nor activation of the checkpoint system could be observed in the vacuolated cells. These results suggest that the R as signaling pathway is involved in the autophagic response caused by ATR overproduction, and tight regulation of ATR protein expression is crucial for cell viability.
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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".