Molecular Cloning and Characterization of the von Hippel-Lindau-Like Protein
Bibliographic record
Abstract
von Hippel-Lindau (VHL) tumor suppressor protein-inactivated in VHL disease and sporadic kidney cancer-is a component of an E3 ubiquitin ligase complex that selectively ubiquitinates the alpha subunit of the hypoxia-inducible factor (HIF) transcription factor for subsequent destruction by the 26S proteasome. Here, we report the identification and characterization of the first VHL homologue, VHL-like protein (VLP), located on chromosome 1q21.2. A 676-bp partial cDNA encoding a 139-amino acid protein that is 78% similar to VHL was isolated by reverse transcription-PCR from human brain cerebellum and several cancer cell lines. The expression of VLP transcript is most abundant in the placenta. Like VHL, VLP contains a beta domain capable of binding HIFalpha. However, unlike VHL, it does not contain a recognizable alpha domain, which is required for nucleating the multiprotein E3 ubiquitin ligase complex. The increased expression of VLP in the presence of VHL attenuated the ubiquitination of HIFalpha and led to the accumulation of downstream HIF target genes. These results taken together indicate that VLP functions as a dominant-negative VHL to serve as a protector of HIFalpha.
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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".