Study on the Putative Contribution of Caspases and the Proteasome to the Degradation of Aph-1a and Pen-2
Bibliographic record
Abstract
The presenilin-dependent gamma-secretase complex is mainly composed of four distinct proteins, namely presenilin 1 or presenilin 2, nicastrin, anterior pharynx defective-1 (Aph-1) and presenilin enhancer (Pen-2). The mechanisms by which the complex is assembled, how its stoichiometry is controlled and how its catalytic activity is regulated are poorly understood. Recent studies indicated that Aph-1 and Pen-2 undergo proteolysis by the proteasome. We have examined the susceptibility of endogenous and overexpressed Aph-1a and Pen-2 to proteolysis by endogenous and purified proteasome as well as by recombinant caspases. We show that endogenous Aph-1a and Pen-2 resist proteolysis by caspases and by the proteasome. Furthermore, we show that unexpected interference of proteasome inhibitors with the cmv promoter region driving expression of Aph-1a and Pen-2 led to artifactual enhancement of overexpressed Aph-1a and Pen-2-like immunoreactivities but that these proteins also resist to in vitro degradation by endogenous and purified proteasome.
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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".