The Hace1 E3 ligase: linking misfolded protein load and oncogenesis
Bibliographic record
Abstract
Hace1 is a new member of the HECT family of E3 protein‐ubiquitin ligases. We previously showed that the Hace1 gene is a tumor suppressor that is inactivated in human Wilms' tumor, and that Hace1‐/‐ mice develop spontaneous tumors. Moreover, various stresses dramatically increases tumor incidence in these mice. The goal of this study is to characterize the role Hace1 is playing in cellular stress and more specifically in misfolded protein handling by the cell. We now show that Hace1 decreases the half‐life of GFP‐Huntingtin‐128Q and eliminates its aggregates in a proteasome independent manner. This indicates that Hace1 may mediate mutant Huntingtin degradation via other pathways such as autophagy. Indeed, Hace1‐/‐ cells show decreased autophagy induction. Fluorescence microscopy suggests that Hace1 is localized to a recently described cellular structure known as IPOD‐ Insoluble Protein Deposit. Using fluorescence recovery after photo‐bleaching we determined that GFP‐Hace1 interacts with IPOD in a highly dynamic manner suggesting that Hace1 plays a role in the function of IPOD rather than being transported to them as aggregates. Taken together, these data indicate that the tumor suppressor Hace1 reduces accumulation of misfolded proteins by promoting autophagy, suggesting that the deregulation of non‐proteasomal processes that manage misfolded protein load may promote oncogenesis in the cell.
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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) | 0.001 | 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 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".