PROX1 regulation of endothelial cell cycle progression
Bibliographic record
Abstract
The homeobox transcription factor PROX1 is necessary for proper lymphatic vessel development. PROX1 upregulates the expression of CYCLIN E1 in both Drosophila melanogaster and mammalian cells. Expression of CYCLIN E1 is controlled by two E2F sites located on either side of the transcriptional start site. We have shown that PROX1 activates a 1 kb Cyclin E1 promoter via a DNA‐binding independent mechanism that requires both E2F sites. We used reporter gene assays to assess PROX1 regulation of Cyclin E1 promoter versions in which the E2F sites were mutated. We infected Human Umbilical Vein Endothelial Cells (HUVEC) with adenovirus encoding PROX1, and used bromodeoxyuridine, proliferating cell nuclear antigen and phosphorylated histone H3 staining to quantify changes in cell cycle progression. We used western blotting to measure protein levels of CYCLIN E1. We observed a decrease in the ability of PROX1 to activate a 206 bp Cyclin E1 promoter when either E2F site was mutated. We noted an increase of CYCLIN E1 in PROX1 infected HUVECs as well as an increased number of cells in S phase. In contrast, there was not a corresponding increase of cells in M phase. We have established that both E2F sites are essential for PROX1 mediated activation of the Cyclin E1 promoter. Our studies have discovered a novel role for PROX1 as a transcriptional co‐activator. The National Cancer Institute of Canada and the Manitoba Health Research Council support this project.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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".