Use of Proteome Arrays to Globally Identify Substrates for E3 Ubiquitin Ligases
Bibliographic record
Abstract
Ubiquitin-protein ligases (E3s) are responsible for target recognition and subsequent modification of selected substrates within the ubiquitin proteasomal system (UPS). Substrates of this pathway are covalently modified by the attachment of ubiquitin usually onto Lys residues. As a result, these modified proteins can be targeted for degradation, endocytosis, protein sorting, subnuclear trafficking, or other fates. Despite the advancements in understanding the underlying mechanisms of the ubiquitin system, the substrates of most E3 enzymes remain largely unknown. Here, we describe the development of a high-throughput method to identify in vitro substrates for E3 ligases on a global proteomic scale. The enzymatic activity (ubiquitylation) and binding of ubiquitin ligases to their substrates are performed using protein (proteome) microarrays as the experimental platform, and using Nedd4/Rsp5 family members as examples of HECT E3 ligases. The in vitro ubiquitylation and binding substrates identified in these screens can provide invaluable insight into the cellular pathways in which E3 ligases participate.
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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 | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 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".