Palmitoyl-transferase 3 promotes mitochondrial antiviral signaling protein degradation by modulating its ubiquitination
Bibliographic record
Abstract
The innate antiviral immunity of humans serves as their first line of defence against viral and microbial illnesses. The retinoic acid-inducible gene I (RIG-I)-like receptor (RLR) signaling pathway requires the mitochondrial antiviral signaling protein (MAVS) to function properly. ZDHHCs, a family of acyltransferases, regulate diverse biological processes via interactions with numerous mammalian proteins and viral proteins. However, the role of ZDHHCs in antiviral innate immunity against RNA viruses remains largely elusive. Here, we show that ZDHHC3 downregulates the RLR signaling pathway. Ectopic ZDHHC3 expression reduces RIG-IN- and SeV-mediated IFN-β promoter activity, IRF3 nuclear transduction, and transcription of the IFN-β and ISG genes. Furthermore, ectopic expression of ZDHHC3 decreases MAVS stability by promoting proteasomal degradation, which can be reversed by MG132 but not CQ. ZDHHC3 interacts with MAVS and promotes its breakdown by increasing K48-linked ubiquitination rather than K63-linked ubiquitination. ZDHHC3 deletion resulted in increased IFN-β promoter activity and transcription of the IFN-β and ISG genes. ZDHHC3 knockdown promotes subsequent antiviral signaling and reduces viral replication, indicating the role of ZDHHC3 in antiviral innate immunity. In addition, the catalytically inactive mutant ZDHHC3 C157S efficiently reversed the IFN-β promoter activity produced by RIG-IN, which was consistent with the results of 2-BP treatment. Collectively, these data show that ZDHHC3 inhibits the RNA virus-triggered signaling cascade by targeting MAVS and provides new insights into the role of ZDHHC3 in antiviral innate immunity.
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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 | 0.001 |
| 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".