Targeting the anaphase promoting complex: common pathways for viral infection and cancer therapy
Bibliographic record
Abstract
INTRODUCTION: The anaphase promoting complex/cyclosome (APC/C) is a ubiquitin ligase involved in regulation of the cell cycle through ubiquitination-dependent substrate proteolysis. Many viral proteins have been shown to interact with the APC/C, derailing cell cycle progression in order to facilitate their own replication. Induction of G(2)/M arrest by viral APC/C inhibition can lead to apoptotic cell death. Some viral proteins cause cytotoxicity specifically in tumour cells, providing evidence that targeting the APC/C could be exploited to selectively eliminate cancer cells. AREAS COVERED: In this review, we provide a summary of studies from viral APC/C interactions over the last decade, as well as recent discoveries identifying the APC/C as a promising target in the context of cancer therapy. EXPERT OPINION: Current therapeutic strategies inducing mitotic arrest rely on activation of the spindle assembly checkpoint (SAC) for their function. Many cancer cells have a weakened SAC and escape apoptosis through mitotic slippage. Recent evidence has demonstrated that targeting the APC/C, particularly the co-activator Cdc20, might be a better alternative. Tumour cells display greater dependency on APC/C function than normal cells and oncogenic transformation can lead to increased mitotic stress, rendering cancer cells more vulnerable to APC/C inhibition.
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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 | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.002 | 0.002 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.002 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.002 | 0.002 |
| Insufficient payload (model declined to judge) | 0.005 | 0.004 |
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".