Abstract 3995: C-terminal fragment of prostate apoptosis response-4 (Par-4) generated by caspase-3 cleavage induces apoptosis in cancer cells
Bibliographic record
Abstract
Abstract Prostate apoptosis response-4 (Par-4) is a ubiquitously expressed pro-apoptotic tumor suppressor protein. Previously, we have shown that Par-4 undergoes caspase-3 mediated cleavage in normal and cancer cells. In the present study, we demonstrated that caspase-3 generated cleaved fragment of Par-4 displays apoptotic activity. Hela cells were transiently transfected with empty or Myc tagged C-terminal fragment of Par-4. The results from immunofluorescence studies revealed that the cleaved fragment of Par-4 is predominantly localized in the nuclear compartment of the cells. Further, cells expressing C-terminal Par-4 fragment underwent significant apoptosis as compared to empty vector transfected cells as measured by flow cytometry using annexin V/PI staining. Next, we tested whether C-terminal fragment of Par-4 follows similar mechanism of apoptosis induction as the full length Par-4 by the inhibition of protein kinase C (PKC)/NF-κB pathway. Western blot analysis revealed that the overexpression of C-terminal Par-4 fragment reduced the protein levels of Bcl-2 and FLIP as compared to empty vector transfected cells. Overexpression of the C-terminal Par-4 fragment also reduced the levels of phosphorylated IαBβ, however, there was no change in the levels of total IαBβ. Interestingly, C-terminal fragment of Par-4 prevented the nuclear mobilization of NF-κB (p65) compared to empty vector transfected cells. On the other hand, NF-κB (p50) protein levels were found to be decreased in cells expressing the C-terminal Par-4 fragment suggesting that C-terminal fragment of Par-4 possesses pro-apoptotic activity and regulates apoptotic induction by inhibiting the nuclear localization and activity of NF-κB in a manner similar to wild type full length Par-4. To conclude, our data suggest that caspase-3 mediated cleavage of Par-4 results in nuclear localization of C-terminal Par-4 fragment which possesses pro-apoptotic activity. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3995. doi:1538-7445.AM2012-3995
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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 | 0.000 | 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".