The ubiquitin ligase Nedd4-2 promotes localization of DNMBP/Tuba to P-bodies under hyperosmotic stress
Bibliographic record
Abstract
] and osmolarity enhances Nedd4-2 enzymatic activity. To globally identify its interactome and substrates in cells under hyperosmotic stress, we performed a BioID screen using miniTurbo with Nedd4-2 as a bait under hyperosmotic (vs. isosmotic) conditions. One of the top hits identified that preferentially binds Nedd4-2 under hyperosmolarity was Dynamin Binding Protein (DNMBP)/Tuba, a known GEF for Cdc42. We then showed that DNMBP is a substrate for Nedd4-2, and that active Nedd4-2 targets DNMBP to P-body condensates under hyperosmotic stress. Moreover, DNMBP itself promotes P-body formation under hyperosmolarity. Both Nedd4-2 and DNMBP are required for the activation of Cdc42 following hyperosmotic treatment, and accordingly, knockout of DNMBP results in suppression of Cdc42 and its downstream effector p38-MAPK. We thus propose that Nedd4-2-mediated targeting of DNMBP to P-bodies under hyperosmotic stress facilitates the activation of Cdc42 by this GEF.
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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".