The Parkinson's disease gene, Parkin, ubiquitinates the endocytic accessory protein Eps15 and regulates endocytosis of the epidermal growth factor receptor /
Bibliographic record
Abstract
Mutations in the parkin gene are responsible for an early-onset autosomal-recessive form of Parkinson's disease. Parkin is an E3 ubiquitin ligase that acts in the covalent attachment of the small protein ubiquitin to substrate proteins. Although many parkin substrates have been identified, none can fully account for the relatively specific death of the dopaminergic neurons in the substantia nigra that occurs in Parkinson's disease. Using an assay that reconstitutes the ubiquitination reaction completely in vitro, I found that not all disease-associated mutations affected parkin's ligase activity. I used this assay to test a potential parkin substrate identified in our lab, the endocytic accessory protein Eps15, which specifically interacts with parkin in a regulated fashion. I found that parkin directly ubiquitinates Eps15 in vitro. Eps15 ubiquitination is known to occur during the process of ligand-induced downregulation of the epidermal growth factor receptor. I found that overexpressing parkin in COS-7 cells inhibited the first step of this process, namely, receptor internalization. These findings add to the knowledge of how pathogenic mutations affect parkin function, and identify a novel role for parkin as a regulator of ligand-induced downregulation of the epidermal growth factor 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 | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.010 | 0.004 |
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".