Phosphorylation of the CCAAT Displacement Protein (CDP)/Cux Transcription Factor by Cyclin A-Cdk1 Modulates Its DNA Binding Activity in G2
Bibliographic record
Abstract
Stable DNA binding by the mammalian CCAAT displacement protein (CDP)/Cux transcription factor was previously found to be up-regulated at the G(1)/S transition as the result of two events, dephosphorylation by the Cdc25A phosphatase and proteolytic processing, to generate an amino-truncated isoform of 110 kDa. In S phase, CDP/Cux was shown to interact with and repress the core promoter of the p21(WAF1) gene. Here we demonstrate that DNA binding by p110 CDP/Cux is down-modulated as cells progress into G(2). Accordingly, cyclin A-Cdk1 was found to bind to CDP/Cux and modulate its DNA binding activity in vitro and in vivo. Interaction with CDP/Cux required the presence of both cyclin A and a cyclin-dependent kinase (Cdk)-activating kinase-activated Cdk1 and involved the Cut homeodomain and a downstream Cy motif. Phosphorylation of serines 1237 and 1270 caused inhibition of DNA binding in vitro. In cotransfection studies, cyclin A-Cdk1 inhibited CDP/Cux stable DNA binding and prevented repression of the p21(WAF1) reporter. In contrast, mutant CDP/Cux proteins in which serines 1237 and 1270 were replaced with alanines were not affected by cyclin A-Cdk1. In summary, our results suggest that the phosphorylation of CDP/Cux by cyclin A-Cdk1 contributes to down-modulate CDP/Cux activity as cells progress into the G(2) phase of the cell cycle.
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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) | 0.001 | 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 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".