The Circadian Transcription Factor CLOCK Modulates Oxidative Stress Resistance via the ACHL– <i>Relish</i> Axis in Drosophila
Bibliographic record
Abstract
Circadian clocks orchestrate temporal regulation of diverse physiological processes, including innate immunity and oxidative stress responses. However, the molecular mechanisms by which core clock components modulate immune tone and redox homeostasis remain elusive. Here, the circadian transcription factor CLOCK (CLK) is identified as a key regulator of oxidative stress resistance in Drosophila melanogaster. Loss of clk significantly enhances survival under oxidative stress, accompanied by constitutive activation of innate immune pathways. Mechanistically, the RNA-binding protein Achilles (ACHL) is identified as a critical downstream effector of CLK. Indeed, CLK drives rhythmic transcription of Achl, and ACHL post-transcriptionally represses the NF-κB homolog Relish by promoting its mRNA degradation, thereby limiting immune overactivation. Disruption of this regulatory cascade, through loss of either clk or Achl, leads to increased Relish abundance, excessive immune gene expression, and enhanced oxidative stress resistance. Genetic suppression of Relish reverses these phenotypes, establishing a functional CLK-ACHL-Relish axis that links circadian output to immune restraint. Importantly, this regulatory mechanism is evolutionarily conserved, as Clock-deficient mammalian cells exhibit increased resistance to oxidative injury. Together, the findings uncover a post-transcriptional immune checkpoint controlled by circadian networks, linking immune quiescence with redox adaptation.
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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 | 0.000 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.003 |
| Science and technology studies | 0.001 | 0.002 |
| Scholarly communication | 0.000 | 0.001 |
| Open science | 0.001 | 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".