Subcellular Dynamics of The VHL Tumor Suppressor: On The Move for HIF Degradation
Bibliographic record
Abstract
The von Hippel-Lindau (VHL) tumor suppressor protein, the recognition component of an E3 ubiquitin ligase complex, recruits the alpha-subunit of the hypoxia-inducible factor (HIFalpha) for oxygen-dependent degradation. The ability of VHL to mediate efficient degradation of HIFalpha is also dependent on its oxygen/pH-regulated subcellular trafficking. Under aerobic conditions, VHL engages in nuclear-cytoplasmic trafficking that requires ongoing transcription and is mediated by a novel nuclear export motif, the transcription-dependent nuclear export motif (TD-NEM). Disease-causing mutations targeting TD-NEM restrain VHL from mediating efficient oxygen-dependent degradation of HIFalpha by altering its subcellular dynamics. In addition, decreasing the extracellular pH, during anaerobic metabolism, stabilizes HIFalpha by triggering the relocalization and static detention of VHL to nucleoli. Together, these recent findings support the critical role of subcellular trafficking and dynamic properties for the function of VHL in promoting HIF regulation and tumor suppression.
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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) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.002 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 0.004 |
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".