Abstract 4970: Convergence of protein kinase and caspase signaling: A mechanism for pathological rewiring of survival pathways by protein kinase CK2
Bibliographic record
Abstract
Abstract Crosstalk between protein kinases and caspases has become evident in light of the observation that phosphorylation within the caspase cleavage motif impairs proteolysis. Given that phosphorylation networks and sensitivity to apoptotic cues are altered in cancer signaling, we sought to investigate if the negative regulation of caspase-mediated degradation by protein phosphorylation is a global mechanism that manifests in changes to cancer cell survival. To systematically investigate the extent to which phosphorylation regulates the caspase degradome, we employed a combination of peptide cleavage assays, database mining, and N-terminomics. These studies revealed that phosphorylation could potentially regulate the cleavage of a significant proportion of caspase substrates. One notable example of phosphorylation-regulated caspase cleavage was the observation that pro-caspase-3 itself is phosphorylated in a manner that prevents subsequent cleavage and activation by upstream initiator caspases. To further examine the role of phosphorylation in regulating the activation of caspase-3, we investigated the phosphorylation of pro-caspase-3-FLAG in HeLa cells transfected with each of the catalytic isoforms of protein kinase CK2 in the presence or absence of the regulatory CK2β subunit. These studies suggest that the activation of caspase-3 could be regulated by CK2 in cells. Coupled with the observations that CK2 is constitutively activity and expressed at elevated levels in a number of different cancers, our observations suggest that increased levels of CK2 could lead to a pathological phosphorylation of pro-caspase-3 to prevent its activation and promote cancer cell survival. 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 4970. doi:1538-7445.AM2012-4970
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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) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.015 | 0.005 |
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".