HIF‐1‐dependent transcriptional activity is required for oxygen‐mediated HIF‐1α degradation
Bibliographic record
Abstract
Hypoxia-inducible factor-1alpha (HIF-1alpha) plays a central role in oxygen homeostasis. In normoxia, HIF-1alpha is a short lived protein, whereas hypoxia rapidly increases HIF-1alpha protein levels by relaxing its ubiquitin-proteasome-dependent degradation. In this study, we show that the p42/p44 MAP kinase cascade, known to phosphorylate HIF-1alpha, does not modulate the degradation/stabilization profile of HIF-1alpha. However, we present evidence that the rate of HIF-1alpha degradation depends on the duration of hypoxic stress. We demonstrate that degradation of HIF-1alpha is suppressed by: (i) inhibiting general transcription with actinomycin D or (ii) specifically blocking HIF-1-dependent transcriptional activity. In keeping with these findings, we postulate that HIF-1alpha is targetted to the proteasome via a HIF-1alpha proteasome targetting factor (HPTF) which expression is directly under the control of HIF-1-mediated transcriptional activity. Although HPTF is not yet molecularly identified, it is clearly distinct from the von Hippel-Lindau protein (pVHL).
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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 | 0.001 |
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".