The MDMX acidic domain competes with the p53 transactivation domain for MDM2 N-terminal domain binding
Bibliographic record
Abstract
The tumor suppressor protein p53 governs many cellular pathways to control genome integrity, metabolic homeostasis, and cell viability. The critical roles of p53 highlight the importance of proper control over p53 in maintaining normal cellular function, with the negative regulators MDM2 and MDMX playing central roles in regulating p53 activity. The interaction between p53 and either MDM2 or MDMX involves the p53 transactivation domain (p53TD) and the N-terminal domains (NTD) of MDM2 or MDMX. Recently, the acidic domain (AD) of MDMX was found to bind to its own NTD, inhibiting the p53-MDMX interaction. Given the established structural and functional similarity between the MDM2 and MDMX NTDs, we hypothesized that the MDMX AD would also directly bind to MDM2 NTD to inhibit p53-MDM2 interaction. Through solution-state nuclear magnetic resonance (NMR) spectroscopy and isothermal titration calorimetry (ITC), we show that the MDMX AD can indeed directly interact with the MDM2 NTD and, as a result, can compete for p53 binding. The MDMX AD is thus able to serve as a regulatory domain to inhibit the MDM2-p53 interaction and may also play a direct role in p53 activation.
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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 | 0.000 |
| Insufficient payload (model declined to judge) | 0.002 | 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".