CASZ1 inhibits cell cycle progression in neuroblastoma by restoring pRb activity
Bibliographic record
Abstract
Dysregulation of cell cycle genes such as Cyclin D1 and Chk1 contributes to the undifferentiated phenotype of neuroblastoma (NB). CASZ1 functions as a tumor suppressor in NB; here we sought to determine how loss of CASZ1 contributes to cell cycle dysregulation in NB. CASZ1 restoration in NB cells delays NB cell cycle progression. The earliest changes occur within 8 h of CASZ1 restoration in SY5Y cells with a 2.8-fold increase in the level of p21, an inhibitor of Cdk2/4. By 16 h, there is a 40% decrease in the steady-state levels of Cdk6. Restoration of CASZ1 decreases Cdk2-dependent cyclins A and E protein levels and Cdk4/6-dependent Cyclin D1 protein levels. The restoration of CASZ1 resulted in a decrease in pRb phosphorylation and a significant reduction of E2F transcriptional activity. Subsequent to the changes in the G 1/S transition, induction of CASZ1 results in a decrease in Cyclin B levels and Cdc25c phosphatase levels, an upstream activator of the G 2/M regulator CyclinB:Cdk1. In addition, induction of CASZ1 results in a decrease in the levels of phospho-Chk1, a key M-phase regulatory kinase. Similar results were found in a NB cell line with MYCN amplification. Taken together, this study indicates that restoration of CASZ1 activates pRb in G 1 and inhibits the G 2/M regulators Cyclin B1 and Chk1, leading to a lengthening of NB cell cycle progression and a subsequent decrease in cell proliferation.
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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 | 0.001 |
| 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".