NEDD8 modification of the von Hippel-Lindau protein in tumour development
Bibliographic record
Abstract
Functional inactivation of the von Hippel-Lindau (VHL) tumour suppressor gene is the cause of the familial VHL disease and most of sporadic renal clear cell carcinomas (RCC). Although most disease-causing pVHL mutations hinder the regulation of the HIF-pathway, every disease-causing pVHL mutant tested to date has failed to promote the assembly of fibronectin matrix, underscoring its potential importance in VHL disease. Here, we report that an ubiquitin-like molecule called NEDD8 covalently modifies pVHL. A non-neddylateable pVHL mutant, while retaining its ability to ubiquitylate HIF, failed to bind and promote the assembly of fibronectin matrix. Expression of the neddylation-defective pVHL in RCC cells was insufficient to suppress the formation of tumours in SCID mice. The results suggest that NEDD8 modification of pVHL plays an important role in fibronectin matrix assembly and in the absence of such regulation, an intact HIF-pathway is insufficient to prevent VHL-associated tumourigenesis.
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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 | 0.000 |
| 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".