Retinoblastoma and the Related Pocket Protein p107 Act as Coactivators of NeuroD1 to Enhance Gene Transcription
Bibliographic record
Abstract
Gene inactivation studies have suggested that the product of the retinoblastoma gene, Rb, is particularly limiting in pituitary pro-opiomelanocortin (POMC)-expressing cell lineages. Indeed, in Rb knock-out mice, these cells develop tumors with high frequency. To understand the implication of limiting Rb expression in these cells, we investigated the action of Rb and its related pocket proteins, p107 and p130, on POMC gene transcription. This led to the identification of the neurogenic basic helix-loop-helix transcription factor, NeuroD1, as a target of Rb action. Rb and to a lesser extent p107, but not p130, enhance NeuroD1-dependent transcription, and this activity appears to depend on direct protein interactions between the Rb pocket and the helix-loop-helix domain of NeuroD1. In vivo, NeuroD is found in a complex that includes Rb and also the orphan nuclear receptor NGFI-B, which mediates corticotropin-releasing hormone activation of POMC transcription. The formation of a similar complex in vitro requires the presence of Rb as a bridge between NeuroD and NGFI-B. In POMC-expressing AtT-20 cells, Rb and p107 are present on the POMC promoter and inhibition of their expression through small interfering RNA decreases POMC mRNA levels. The action of Rb and its related proteins on POMC transcription may contribute to the establishment and/or maintenance of the differentiation phenotype.
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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 | 0.001 |
| 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".