βTrCP-dependent degradation of CDC25B phosphatase at the metaphase-anaphase transition is a pre-requisite for correct mitotic exit
Bibliographic record
Abstract
The dual-specificity phosphatase CDC25B, a key regulator of CDK/Cyclin complexes, is considered as the starter of mitosis. It is an unstable protein, degraded by the proteasome, but often overexpressed in various human cancers. Based on experiments carried out in Xenopus eggs, and on video microscopy studies in mammalian cells, it has been proposed that human CDC25B degradation is dependent of the F-box protein βTrCp, but the involvement of this latter protein was not formally demonstrated yet. Here, we show that indeed, in mammalian cells, βTrCp participates to CDC25B turnover, and is required for the complete degradation of CDC25B at the metaphase-anaphase transition. Using a stabilized mutant of CDC25B, which cannot interact anymore with βTrCp, we further show that, during late phases of mitosis, reduced degradation of CDC25B leads to an extended window of expression of the protein, which in turn induces a delay in mitosis exit and entails mitotic defects such as chromosomes missegregation. These findings show that a dysfunction in the rapid and precisely controlled degradation of CDC25B at the metaphase-anaphase transition is sufficient to cause genomic instability and suggest that, in human tissues, pathologic stabilization or untimed expression of CDC25B could contribute to tumorigenesis.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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 | 0.000 |
| 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".