Abstract 4093: Prostate apoptosis response-4 (Par-4): A novel substrate of caspase-3 during apoptosis
Bibliographic record
Abstract
Abstract Prostate apoptosis response-4 (Par-4) is a ubiquitously expressed pro-apoptotic tumor suppressor protein. Par-4 is known to selectively induce apoptosis in cancer cells either by activating apoptosis or by inhibiting cell survival. Here, we show, for the first time, that Par-4 is a novel substrate of caspase-3 during apoptosis. We found that Par-4 is cleaved during cisplatin-induced apoptosis in human normal and cancer cell lines. Caspase-3-deficient MCF-7 cells did not show Par-4 cleavage in response to cisplatin treatment. This Par-4 cleavage was concomitant with Parp cleavage and generated a C-terminal fragment of approx. 25kDa. The cleavage of Par-4 was completely inhibited by Z-VAD-fmk (an inhibitor of caspase like protease) suggesting that caspase-3 like activity is involved in the cleavage of Par-4. Consistently, recombinant caspase-3 efficiently cleaved Par-4 in vitro for all cell lines tested, suggesting the involvement of this protease in Par-4 processing in vivo. Overexpression of caspase-3 in PC-3 cells increased caspase-3 activity, which further resulted in the cleavage of Par-4 in these cells. However, overexpression of a catalytic mutant caspase-3 (C163A) failed to induce Par-4 cleavage. Further, restoration of caspase-3 in MCF-7 cells showed a decrease in Par-4 levels with the appearance of the cleaved fragment. The cleavage of Par-4 in caspase-3 expressing MCF-7 cells was efficiently blocked by a caspase-3 inhibitor. These results establish for the first time that Par-4 is a novel substrate of caspase-3 both in vitro and in vivo. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4093. doi:10.1158/1538-7445.AM2011-4093
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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 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 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".