Identification and Validation of an Interaction between the E3 Ubiquitin Ligase WWP1 and the Transcriptional Co-Activator WBP2 in the Human Heart
Bibliographic record
Abstract
Abstract Impaired proteostasis is one of the cellular hallmarks of aging, and the ubiquitin-proteosome system is a fundamental driver of proteostasis. As an E3 ubiquitin ligase, WW-domain containing protein 1 (WWP1) expression and activity are tightly regulated in cells, while its deregulation has been described in cancer, in neurodegenerative diseases, and in heart failure. However, the protein-protein interaction network of WWP1 is understudied, particularly in the heart. Here, we conducted a yeast-two hybrid (Y2H) screen of a human heart library and identified 21 putative WWP1 interactors, including 12 whose expression and potential function in the heart were previously unappreciated. Chief among these was WBP2 (WW domain binding protein 2), an oncogenic transcriptional co-activator. Utilizing immunofluorescence, it was confirmed that endogenous WWP1 co-localizes with WBP2 in human heart tissue, and, using the Y2H system, we showed that this interaction is dependent upon the associations between WW domains 1 and 3 from WWP1 and PY domains 2 and 3 of WBP2. In total, these data serve as a launching pad to identify broader protein networks regulated by WWP1 and the regions of interaction which might be targetable to reduce hallmarks of cellular aging.
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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 | 0.000 |
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 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".