The hGID <sup>GID4</sup> E3 ubiquitin ligase complex targets ARHGAP11A to regulate cell migration
Bibliographic record
Abstract
Abstract The human CTLH/GID (hGID) complex emerged as an important E3 ligase regulating multiple cellular processes, including cell cycle progression and metabolic activity. However, the range of biological functions controlled by hGID remains unexplored. Here, we show that the hGID substrate receptor GID4 regulates cell growth and migration. Biochemical and cellular assays combined with proximity-dependent biotinylation (BioID2) revealed that the hGID GID4 E3-ligase targets the Rho-GAP ARHGAP11A for degradation. Depletion of GID4 or impeding the GID4 substrate binding pocket impairs motility and directed cell movement, whereas knockdown of ARHGAP11A significantly restores the cell migration defect. We found that GID4 controls cell migration by degrading ARHGAP11A thereby preventing its accumulation at the cell periphery where it inactivates RhoA activity. Together, we identified a unique function for GID4, as well as a wide range of substrate profiles beyond Pro/N-degron motifs, which pave the way for deciphering additional pathways regulated by hGID E3 ligase activity through its GID4 substrate receptor.
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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) | 0.003 | 0.001 |
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".