The CCT[alpha] membrane‐binding domain is required for nuclear export during apoptosis
Bibliographic record
Abstract
CTP:phosphocholine cytidylyltransferase (CCT)∞, the rate‐limiting nuclear enzyme in phosphatidylcholine synthesis, translocates to nuclear membranes in response to fatty acid and diacylglycerol activators. In addition, the apoptotic agent farnesol (FOH) promotes CCT∞ translocation to the nuclear envelope (NE) and nucleoplasmic reticulum (NR), and export from the nucleus. Here we investigated the contribution of the CCT∞ membrane binding (M) and phosphorylation (P) domains to FOH‐mediated nuclear export. M and P domain mutants of CCT∞ were V5‐ or GFP‐tagged, expressed in MT58 cells and localized by fluorescence microscopy. P domain mutants with 16 Ser residues changed Ala (16S→A) or Glu (16S→E) were localized to the nucleus and exported upon FOH treatment. Mutation of Pro‐directed phosphorylation sites (CCT 7SP→AP) or deletion of the P domain (CCT 314) produced similar results. CCT∞ mutated at basic residues (R245Q, K248,250,252,254,259,261,266Q) in domain M did not translocate to the NE or NR, nor was it exported in response to FOH. Mutation of 5 of these basic residues (R245Q, K248,252,259,266Q) did not affect translocation or nuclear export. Mutation of acidic residues in CCT∞ domain M (E257,268,279Q) resulted in increased association with the NE and NR under basal conditions, and export in response to FOH. CCT∞ with the P and M domain deleted (CCT 236) did not associate with membranes or export from the nucleus. These data indicate that membrane association of CCT∞ via Domain M is necessary for nuclear export during apoptosis. (Supported by CIHR and IWK)
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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 | 0.001 | 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".