Phosphorylation of Sp1 by Cyclin-dependent Kinase 2 Modulates the Role of Sp1 in CTP:Phosphocholine Cytidylyltransferase α Regulation during the S Phase of the Cell Cycle
Bibliographic record
Abstract
Phosphatidylcholine is the major lipid component in mammalian membranes. Phosphatidylcholine synthesis increases in C3H10T1/2 fibroblasts during the G(1) and S phases of the cell cycle. Previous studies demonstrated that the mRNA encoding CTP:phosphocholine cytidylyltransferase alpha (CTalpha) increases during S phase (Golfman, L. S., Bakovic, M., and Vance, D. E. (2001) J. Biol. Chem. 276, 43688-43692) and that this activation is driven by increased binding of Sp1 to the CTalpha promoter (Banchio, C., Schang, L. M., and Vance, D. E. (2003) J. Biol. Chem. 278, 32457-32464). We now demonstrate that cyclin-dependent kinase 2 (CDK2) phosphorylation of Sp1 activates CTalpha transcription during S phase. Sp1 binds in a phosphorylated state to the CTalpha promoter. Sp1 binding is enhanced by association with cyclin A/E and CDK2, both in vivo and in vitro. In cells that overexpress Sp1, co-expression of cyclin A and CDK2 induces a high and constant level of CTalpha expression, whereas reduction in the expression of cyclin A, cyclin E, and CDK2 eliminates the induction of CTalpha expression in S phase. Furthermore, CTalpha expression is decreased in cells overexpressing a dominant-negative form of CDK2 and in cells treated with the CDK2 kinase inhibitors roscovitine and olomoucine. These results enhance our understanding of the regulatory mechanisms involved in the expression of CTalpha in preparation for cell division.
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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 | 0.001 |
| 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".