Induction of apoptosis by lipophilic activators of CTP:phosphocholine cytidylyltransferase α (CCTα)
Bibliographic record
Abstract
Farnesol (FOH) inhibits the CDP-choline pathway for PtdCho (phosphatidylcholine) synthesis, an activity that is involved in subsequent induction of apoptosis. Interestingly, the rate-limiting enzyme in this pathway, CCTalpha (CTP:phosphocholine cytidylyltransferase alpha), is rapidly activated, cleaved by caspases and exported from the nucleus during FOH-induced apoptosis. The purpose of the present study was to determine how CCTalpha activity and PtdCho synthesis contributed to induction of apoptosis by FOH and oleyl alcohol. Contrary to previous reports, we show that the initial effect of FOH and oleyl alcohol was a rapid (10-30 min) and transient activation of PtdCho synthesis. During this period, the mass of DAG (diacylglycerol) decreased by 40%, indicating that subsequent CDP-choline accumulation and inhibition of PtdCho synthesis could be due to substrate depletion. At later time points (>1 h), FOH and oleyl alcohol promoted caspase cleavage and nuclear export of CCTalpha, which was prevented by treatment with oleate or DiC8 (dioctanoylglycerol). Protection from FOH-induced apoptosis required CCTalpha activity and PtdCho synthesis since (i) DiC8 and oleate restored PtdCho synthesis, but not endogenous DAG levels, and (ii) partial resistance was conferred by stable overexpression of CCTalpha and increased PtdCho synthesis in CCTalpha-deficient MT58 cells. These results show that DAG depletion by FOH or oleyl alcohol could be involved in inhibition of PtdCho synthesis. However, decreased DAG was not sufficient to induce apoptosis provided nuclear CCTalpha and PtdCho syntheses were sustained.
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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 | 0.000 | 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 | 0.000 |
| 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".