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 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 | 0.001 |
| 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) | 0.006 | 0.002 |
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".