The adenoviral protein E4orf4: a probing tool to decipher mechanical stress-induced nuclear envelope remodeling in tumor cells
Bibliographic record
Abstract
The human adenovirus (Ad) type 2/5 early region 4 (E4) ORF4 protein (E4orf4) exerts a remarkable tumor cell-selective killing activity in mammalian cells. This indicates that E4orf4 can target tumor cell-defining features and is a unique tool to probe cancer cell vulnerabilities. Recently, we found that E4orf4, through an interaction with the polarity protein PAR3, subverts nuclear envelope (NE) remodeling processes in a tumor cell-selective manner. In this Perspective, we outline mechanical signals that modify nuclear dynamics and tumor cell behavior to highlight potential mechanisms for E4orf4's tumoricidal activity. Through an analysis of E4orf4's cellular targets, we define a protein subnetwork that comprises phosphatase systems interconnected to polarity protein hubs, which could contribute to enhanced NE plasticity. We infer that elucidating E4orf4's protein network at a functional level could uncover key mechanisms of NE remodeling that define the tumor cell phenotype.
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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 | 0.000 | 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) | 0.000 | 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".