Functional Analysis of the Contribution of HIF-1α Proline 402 to the Interaction with VHL
Bibliographic record
Abstract
Hypoxia-inducible factor 1 alpha (HIF-1α) is involved in transcription of hypoxia-inducible genes. In normoxia, it binds von Hippel-Lindau (VHL) resulting in ubiquitin-proteasome degradation. This requires hydroxylation at prolines 564 (P564) or 402 (P402) within the oxygen-dependent degradation (ODD) domain. P402 hydroxylation only occurs at higher oxygen concentrations. Its specific contribution to the HIF-1α-VHL interaction is unknown. It was hypothesized that loss of P402 in normoxia will dampen the HIF-1α-VHL interaction. HA-tagged ODD constructs (WT, P402A, P564G, and P402A/P564G) were generated. FLAG-VHL co-immunoprecipitation was lower for P402A compared to WT. In vitro ubiquitination decreased with P402 mutation when P564 was also mutated. Cycloheximide chase analysis showed that P402 loss had no significant effect on ODD half-life. These results indicate a secondary role for P402 in the HIF-1alpha-VHL interaction. Elucidating the details of P402’s role in the interaction of HIF-1alpha with VHL will enhance the understanding of mammalian oxygen sensing and ubiquitin-proteasome pathways.
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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".