Transcription-Independent p53 Apoptosis Requires Caspase-8
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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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) | 0.001 | 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 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".