CS-01 * THE PHOSPHORYLATION OF ATOH1 LEADS TO ITS DEGRADATION MEDIATED BY THE E3 UBIQUITIN LIGASE HUWE1 IN GRANULE NEURON PROGENITORS
Bibliographic record
Abstract
Medulloblastoma is the most common malignant pediatric brain tumor and is divided in four subgroups by gene profiling. The well-known subgroup harboring an activation of the Sonic Hedgehog (SHH)/Patched (PTCH) pathway shows an upregulation of the pro-neural basic helix-loop-helix transcription factor Atoh1. Atoh1 is essential for cerebellum development and more specifically for the formation of the granule neuron progenitors (GNPs), which are the cells of origin of SHH induced medulloblastoma. In tumoral context, Atoh1 acts as a pro-tumor factor in cooperation with SHH/PTCH pathway and its inhibition prevents medulloblastoma proliferation in vitro and in vivo. However, to date, mechanisms underlying Atoh1 regulation remained to be elucidated. We recently found that the mitogen SHH, by regulating Atoh1 phosphorylation, can protect Atoh1 against Huwe1-mediated degradation. We also showed that Atoh1 degradation by the E3 ubiquitin ligase Huwe1 was required for proper cerebellum development. Moreover, low expression of HUWE1 in human Sonic Hedgehog medulloblastoma subgroup was associated with a poor survival rate of patients. Together, we uncovered a signaling pathway that controls the balance between neuronal proliferation and differentiation in GNPs and that could be further targeted in order to elaborate new therapeutic strategies.
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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 | 0.001 | 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".