Regulation of cell cycle progression by forkhead transcription factor FOXO3 through its binding partner DNA replication factor Cdt1
Bibliographic record
Abstract
To ensure genome stability, DNA must be replicated once and only once during each cell cycle. Cdt1 is tightly regulated to make sure that cells do not rereplicate their DNA. Multiple regulatory mechanisms operate to ensure degradation of Cdt1 in S phase. However, little is known about the positive regulators of Cdt1 under physiological conditions. Here we identify FOXO3 as a binding partner of Cdt1. FOXO3 forms a protein complex with Cdt1, which in turn blocks its interaction with DDB1 and PCNA. Conversely, FOXO3 depletion facilitated the proteolysis of Cdt1 in unperturbed cells. Intriguingly, FOXO3 deficiency resulted in impaired S-phase entry and reduced cell proliferation. We provide data that FOXO3 knockdown mimics Cdt1 down-regulation and affects G1/S transitions. Our results demonstrate a unique role of FOXO3 in binding to Cdt1 and maintaining its level required for cell cycle progression.
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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".