The role of USP19 deubiquitinating enzyme in regulating cell proliferation
Bibliographic record
Abstract
We previously identified the USP19 deubiquitinating enzyme. To further characterize the functions of USP19, we used siRNA to deplete this enzyme in cultured cells. Depletion of USP19 in FR3T3 fibroblasts resulted in an impairment of cell growth, delay in entry into S phase and accumulation of p27Kip1, an inhibitor of G1 to S phase progression. This increased p27Kip1 upon USP19 depletion was due to a decrease in the rate of degradation of p27Kip1 in G0 and G1 phases, but not at the G1/S transition. The increased p27Kip1 in USP19 depleted FR3T3 cells was associated with reduced levels of KPC1, the catalytic subunit of a ubiquitin protein ligase for p27Kip1, but no changes in levels of Pirh2 or Skp2, other ligases for p27Kip1. KPC1 was ubiquitinated in vivo and stabilized by proteasome inhibitors and by overexpression of USP19, and it also coimmunoprecipitated with USP19. Cell growth impairment upon USP19 depletion was partially reversed in cell lines stably expressing KPC1 or in p27Kip1â/â MEF cells. These findings indicated that in normal fibroblasts, USP19 exerts its effects on cell proliferation through KPC1/ p27Kip1 dependent mechanisms, by deubiquitinating and stabilizing KPC1 which in turn leads to increased ubiquitination of p27Kip1, and also by a KPC1/ p27Kip1 independent pathway(s).
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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 | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.001 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| 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".