Oxysterol‐ and cholesterol‐dependent translocation of CTP:phosphocholine Cytidylyltransferase to the nuclear envelope
Bibliographic record
Abstract
Oxysterols potently regulate cholesterol, phospholipid and sphingomyelin synthesis. Here, we investigated how 22‐, 25‐, and 26‐hydroxycholesterol (22OH, 25OH, and 26OH, respectively) stimulate the CDP‐choline pathway for phosphatidylcholine (PtdCho) synthesis using CHOK1 and CHO cells that express a sterol‐resistant mutant of sterol regulatory element binding‐protein (SREBP)‐cleavage activating protein (CHOSCAP D443N). Analysis of [3H]choline‐labelled metabolites showed that oxysterols activated CTP:phosphocholine cytidylyltransferase (CCTα) and increased PtdCho synthesis. Oxysterols also promoted complete localization of CCTα to the nuclear envelope and intranuclear tubules in both CHO‐SCAP D443N and CHOK1 cells. Cholesterol was required for this effect since depletion with cyclodextrin or lovastatin resulted in reduced translocation and activation of PtdCho synthesis. In vitro , CCTα activity was stimulated by PtdCho vesicles containing oxysterols. Synergistic activation of CCTα by vesicles with 25OH and cholesterol suggested that the membrane environment created by the combination of these two sterols has unique stimulatory properties that could be reproduced in CHO‐SCAP‐D443N cells. Thus 22, 25, and 26‐OH promotes translocation and activation of CCTα at the nuclear envelope in a cholesterol‐dependent manner. (Supported by CIHR and IWK)
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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 | 0.000 |
| 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) | 0.002 | 0.001 |
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".