Proprotein convertase subtilisin/kexin type 9 inhibits interferon β expression through interacting with <scp>ATF</scp>‐2
Bibliographic record
Abstract
Proprotein convertase subtilisin/kexin type 9 (PCSK9) regulates lipid metabolism. A mutual interplay of lipid homeostasis and innate immune system has been increasingly recognized. We, therefore, studied the effect of PCSK9 on interferon (IFN) β expression. We show that PCSK9 decreases IFNβ promoter/enhancer activity, mRNA and protein levels, and its downstream 2',5'-oligoadenylate synthetase-1 mRNA level. ProPCSK9, but not the cleaved PCSK9, down-regulates IFNβ promoter/enhancer activity. Moreover, PCSK9 decreases IFNβ promoter/enhancer activity through the positive regulatory domain IV region where the activating transcription factor-2 (ATF-2)/c-Jun heterodimer binds. Mechanistically, we demonstrate an interaction between PCSK9 and ATF-2, which reduces ATF-2/c-Jun dimerization and ATF-2/c-Jun binding to the IFNβ enhancer. This novel function of PCSK9 should have important implications in optimizing the clinical use of PCSK9 inhibitors.
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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) | 0.002 | 0.001 |
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".