O-GlcNAcylation of SKN-1 modulates the lifespan and oxidative stress resistance in Caenorhabditis elegans
Bibliographic record
Abstract
In C. elegans, the transcription factor skinhead-1 (SKN-1), the ortholog of human NF-E2-related factor 2 (Nrf-2), plays important roles in oxidative stress defense and aging processes. It has been documented that the activity of SKN-1 is regulated by its phosphorylation modification. However, whether other posttranslational modifications of SKN-1 affect its function remains unclear to date. Here we report, for the first time, that SKN-1 is O-GlcNAcylated at Ser470 and Thr493 by O-GlcNActransferase OGT-1. By generating the double mutations of Ser470/Thr493 in the wild type and skn-1(zu67) worms, respectively, we found that disruption of O-GlcNAc modification on SKN-1 repressed the accumulation of SKN-1 in the intestinal nuclei, and decreased the activities of SKN-1 in modulating lifespan and oxidative stress resistance. Moreover, under oxidative stress, SKN-1 was highly O-GlcNAcylated, resulting in the decrease of GSK-3-mediated phosphorylation at Ser483 adjacent to the O-GlcNAcylated residues (Ser470 and Thr493). These data suggest that O-GlcNAcylation of SKN-1 is crucial for regulating lifespan and oxidative stress resistance via the crosstalk with its phosphorylation in C. elegans. These findings have important implications for studying the functions of O-GlcNAcylation on Nrf-2 in human aging-related diseases.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 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 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 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 teacher head, 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".