Targeting Cancer Cells via N-degron-based PROTACs
Bibliographic record
Abstract
In mammals, protein degradation is mediated selectively by the ubiquitin proteasome system (UPS) and the autophagic-lysosomal system. Over the past decades, N-degron pathways have been shown to be responsible for the selective degradation of proteins that harbor destabilizing N-terminal motifs. Recent studies have employed these pathways in the development of proteolysis targeting chimeras (PROTACs) composed of a degradation module linked to a substrate recognition domain to target proteins encoded by cancer-related genes for proteasomal destruction. Herein we provide an overview of PROTACs in the context of the N-degron concept and address the application of this technique to curb the migration and invasion of cancer cells, with a focus on the far-reaching potential of exploiting N-degron pathways for therapeutic purposes.
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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 | 0.000 |
| 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".