The Targeting of the Proteasomal Regulatory Subunit S2 by Adenovirus E1A Causes Inhibition of Proteasomal Activity and Increased p53 Expression
Bibliographic record
Abstract
Although adenovirus early region 1A (AdE1A) can modulate protein expression through its interaction with transcriptional regulators it can also influence the ability of the cell to degrade proteins by binding to components of the 26 S proteasome. We demonstrate here that AdE1A interacts with the S2 subunit of the 19 S regulatory complex in addition to the ATPase subunits S4 and S8 previously identified. S2 forms complexes with both the 13 and 12 S AdE1A proteins both in vivo and in vitro. Mutational analysis has shown direct binding through a short sequence toward the N terminus of conserved region 2 of AdE1A, which encompasses the LXCXE motif, involved in interaction with the pRb family of proteins. In vivo, additional contacts are made between AdE1A and proteasomal components, as well as within the proteasome, such that deletion of the N-terminal region of E1A as well as part of conserved region 2 is required to completely disrupt S2 binding. Mutation of AdE1A, which disrupts complex formation with S2, results in the loss of its ability to stabilize the p53 protein. Similarly down-regulation of S2 expression using small interfering RNAs leads to the inhibition of p53 degradation. These effects were observed in normally growing cells and those subjected to UV irradiation. Furthermore, AdE1A had no effect on the Mdm2-mediated ubiquitination of p53. We suggest therefore that interaction of AdE1A with S2, as well as with the ATPases S4 and S8, directly causes inhibition of proteasomal activity and consequent increase in the protein levels of p53.
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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 | 0.001 | 0.001 |
| 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 | 0.001 |
| 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".