C-terminal deletion of NOTCH1 intracellular domain (N1ICD) increases its stability but does not amplify and recapitulate N1ICD-dependent signalling
Bibliographic record
Abstract
Abstract Since the generation of a mouse strain conditionally expressing the active intracellular domain of Notch1 (N1 ICD ), many laboratories have exploited this model (Rosa N1-ICD ) to assess the impact of constitutive Notch1 signalling activation in normal and pathological processes. It should be underscored that Cre-recombination leads to the expression of a C-terminally truncated form of N1 ICD (N1 ICDdC ) in the Rosa N1-ICD mutant mice. Given that no studies were undertaken to delineate whether deletion of this region leaves intact N1 ICD function, stable cell lines with single targeted integration of inducible N1 ICD and N1 ICDdC were generated. We found that C-terminal deletion of N1 ICD stabilized the protein but did not promote the activity of Notch responsive promoters. Furthermore, despite higher expression levels, N1 ICDdC failed to phenocopy N1 ICD in the promotion of anchorage-independent growth. Our results thus suggest that the C-terminal region of N1 ICD plays a role in shaping the Notch response. Therefore, it should be taken into consideration that N1 ICD is truncated when interpreting phenotypes of Rosa N1-ICD mutant mice.
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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 | 0.002 | 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 | 0.001 | 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".