Ubiquitin E3 ligase β‐TrCP negatively regulates surface protein of hepatitis B virus
Bibliographic record
Abstract
Abstract Chronic hepatitis B (CHB) still cannot be cured currently, while the pursuit of a functional cure seems to be an accessible goal, in which the condition mainly depends on the serum hepatitis B surface antigen (HBsAg) levels. HBsAg may be downregulated by protein ubiquitination, which may facilitate finding a new potential intervention target for functional cure of CHB. We confirmed that β‐transducin repeat‐containing protein (β‐TrCP) was the E3 ubiquitin ligase of HBsAg. β‐TrCP specifically downregulated the expression of Myc‐HBsAg. The degradation of Myc‐HBsAg occurred via the proteasome pathway. Knockdown of β‐TrCP increased Myc‐HBsAg levels in HepG2 cells. The study further indicated that β‐TrCP could affect the K48‐linked polyubiquitin chain by acting on Myc‐HBsAg. The GS 137 G motif of HBsAg protein is required for β‐TrCP‐mediated degradation. Furthermore, we found that β‐TrCP could significantly inhibit both intracellular and extracellular HBsAg levels produced by pHBV‐1.3. Our study demonstrated that the E3 ubiquitin ligase β‐TrCP induces K48‐linked polyubiquitination of HBsAg, promotes the ubiquitination degradation of HBsAg, and downregulates intra‐ and extracellular HBsAg levels. Therefore, using the ubiquitination degradation pathway of HBsAg, it is possible to reduce HBsAg levels in CHB patients, which may be helpful in obtaining the goal of functional cure in the treatment of CHB patients.
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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 | 0.002 | 0.006 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 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 | 0.001 |
| 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 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".