Transcription-Independent p53 Apoptosis Requires Caspase-8
Why this work is in the frame
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Bibliographic record
Abstract
The tumor suppressor p53 is involved in cell-cycle arrest and apoptosis in response to several intrinsic signals (DNA damage) and extrinsic signals (growth factor deprivation and hypoxia). Apoptosis triggered by p53 can occur through two mechanisms: one that requires the transcriptional activation of genes by p53 and one that is transcription-independent. Ding et al. explored the mechanisms by which p53 causes transcription-independent apoptosis (TI-apoptosis) using cell-free apoptosis assays and cell-based assays that relied on transfection experiments to trigger apoptosis by a mutant of p53 that lacked transcriptional regulatory activity. TI-apoptosis relied on the activation of caspase-8, which was found in a large (600-kD complex that did not contain the pro-apoptotic, death domain-containing protein FADD). In cells, TI-apoptosis required caspase-8 and caspase-9; however, in cell-free extracts, caspase-8 alone was sufficient to trigger cleavage of caspase-3. Finally, TI-apoptosis was blocked by cotransfection of the anti-apoptotic protein Bcl-2, and irradiation caused the cleavage of the pro-apoptotic protein BID. Thus, the authors propose that the p53-triggered TI-apoptosis involves the activation of caspase-8 during the formation of the novel 600-kD complex, which then leads to cleavage of BID and activation of the mitochondrial caspase-9 apoptotic pathway. Ding, H.-F., Lin, Y.-L., McGill, G., Juo, P., Zhu, H., Blenis, J., Yuan, J., and Fisher, D.E. (2000) Essential role for caspase-8 in transcription-independent apoptosis triggered by p53. J. Biol. Chem. 275 : 38905-38911. [Abstract] [Full Text]
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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 | 0.001 |
| 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) | 0.003 | 0.001 |
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 it