Degradation of regulator of calcineurin 1 (RCAN1) is mediated by both chaperone‐mediated autophagy and ubiquitin proteasome pathways
Bibliographic record
Abstract
Regulator of calcineurin 1 (RCAN1), a gene identified from the critical region of Down syndrome, has been implied in pathogenesis of Alzheimer's disease (AD). RCAN1 expression was shown to be increased in AD brains; however, the mechanism of RCAN1 gene regulation is not well defined. The present study was designed to investigate the molecular mechanism of RCAN1 protein degradation. In addition to being degraded through the ubiquitin proteasome pathway, we found that lysosomal inhibition markedly increased RCAN1 protein expression in a time- and dosage-dependent manner. Inhibition of macroautophagy reduced RCAN1 expression, indicating that RCAN1 degradation is not through a macroautophagy pathway. However, disruption of chaperone-mediated autophagy (CMA) increased RCAN1 expression. Two CMA recognition motifs were identified in RCAN1 protein to mediate its degradation through a CMA-lysosome pathway. A promoter assay further demonstrated that inhibition of RCAN1 degradation in cells reduced calcineurin-NFAT activity. Dysfunctions of ubiquitin-proteasome and autophagy-lysosome pathways have been implicated in neurodegenerative diseases. Therefore, elucidation of RCAN1 degradation by a ubiquitin proteasome pathway and CMA-lysosome pathway in the present study may greatly advance our understanding of AD pathogenesis.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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".