Identifying Novel Substrates of Ubiquitin-Specific Protease 7 (USP7) And Speckle-Type POZ (Pox Virus and Zinc Finger) Protein (SPOP)
Bibliographic record
Abstract
Speckle-type POZ protein (SPOP), an E3 ubiquitin ligase adaptor protein, and ubiquitin-specific protease 7 (USP7), a deubiquitinating enzyme, have previously been implicated in prostate cancer pathogenesis. The objective of this project was to identify novel substrates of SPOP and USP7 to provide insight on the molecular mechanisms contributing to prostate cancer. Employing biochemical and cellular biology techniques, we identified, murine double minute 2 (MDM2), an E3 ubiquitin ligase, as a potential substrate of SPOP. We demonstrated that SPOP interacts with MDM2 through its MATH domain in vitro and negatively regulates its stability in vivo. Moreover, we identified sirtuin 2 (SIRT2), an NAD+-dependent deacetylase, as a novel substrate of USP7. We demonstrated that USP7 interacts and regulates the stability of SIRT2 in vivo. Collectively, our results suggest that SPOP and USP7 through the regulation of MDM2 and SIRT2, may contribute to prostate cancer, however further studies are required to verify this.
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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 | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.005 | 0.002 |
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".