MDM2
inhibit
Suppresses p53 stability and transcriptional activity through ubiquitin-mediated control.
Unified output view for the TP53 protein interaction pipeline, combining network topology, source overlap, evidence distribution, top interactors, and downstream GNN model performance.
Focused view of the highest-signal first-hop TP53 neighborhood, with interactor-interactor edges preserved for graph learning.
| Interactor | Sources | Source Count | Max Score |
|---|---|---|---|
| ATM | BioGRID,STRING | 2 | 999 |
| BCL2 | BioGRID,STRING | 2 | 999 |
| BCL2L1 | BioGRID,STRING | 2 | 999 |
| BRCA1 | BioGRID,STRING | 2 | 999 |
| CDKN1A | BioGRID,STRING | 2 | 999 |
| CDKN2A | BioGRID,STRING | 2 | 999 |
| CHEK2 | BioGRID,STRING | 2 | 999 |
| CREBBP | BioGRID,STRING | 2 | 999 |
| DAXX | BioGRID,STRING | 2 | 999 |
| EP300 | BioGRID,STRING | 2 | 999 |
| HDAC1 | BioGRID,STRING | 2 | 999 |
| HIF1A | BioGRID,STRING | 2 | 999 |
| HIPK2 | BioGRID,STRING | 2 | 999 |
| HSP90AA1 | BioGRID,STRING | 2 | 999 |
| MDM2 | BioGRID,STRING | 2 | 999 |
| Evidence Type | Count |
|---|---|
| Affinity Capture-MS | 1134 |
| STRING_combined | 766 |
| Affinity Capture-Western | 454 |
| Proximity Label-MS | 225 |
| Negative Genetic | 141 |
| Reconstituted Complex | 120 |
| Two-hybrid | 107 |
| Synthetic Growth Defect | 96 |
Readable direct-link view in the style of TP53 - 83% - ATM, using the interaction support score as confidence.
Prioritized proteins for restoring mutant p53 pathway activity, combining TP53 mutation burden, hotspot distribution, reporter-loss context, and TP53-centered network support.
Hotspot codons: 273:4867, 248:4674, 175:3423, 245:2127, 282:1737
Dominant domains: DNA binding, HCD IV - DNA binding, HCD V - DNA binding
Reporter medians: WAF1 2.7, MDM2 8.7, BAX 7.5, GADD45 3.2
Most pathogenic missense variants cluster in the DNA-binding region (98.7%), so restoring transcriptional output is the main biological objective.
The reporter-loss score is high (0.94), indicating broad collapse of canonical p53 target-gene activity.
The strongest inhibition-side targets are MDM2, MDM4, SIRT1, which points to the MDM2/MDM4 and deacetylase axis as the clearest suppression program.
The top restoration-side targets are EP300, CREBBP, HIPK2, highlighting acetylation and DNA-damage signaling as the most plausible recovery routes.
| Mechanism | Count |
|---|---|
| acetyltransferase | 3 |
| dna damage kinase | 3 |
| negative regulator | 2 |
| deacetylase | 2 |
| checkpoint kinase | 2 |
inhibit
Suppresses p53 stability and transcriptional activity through ubiquitin-mediated control.
inhibit
Blunts p53 transactivation and cooperates with MDM2 in dampening p53 function.
inhibit
Removes activating acetylation marks from p53 and weakens transcriptional recovery.
activate or support
Acetyltransferase activity can restore transcriptional competence to p53-responsive programs.
inhibit
Chromatin and p53 deacetylation can suppress mutant p53 reactivation programs.
activate or support
Supports p53-dependent transcription through acetylation and co-activation functions.
| Target | Priority | Action | Class | Sources | Rationale |
|---|---|---|---|---|---|
| MDM2 | 99.47 | inhibit | negative regulator | BioGRID,STRING | Suppresses p53 stability and transcriptional activity through ubiquitin-mediated control. |
| MDM4 | 98.47 | inhibit | negative regulator | BioGRID,STRING | Blunts p53 transactivation and cooperates with MDM2 in dampening p53 function. |
| SIRT1 | 94.75 | inhibit | deacetylase | BioGRID,STRING | Removes activating acetylation marks from p53 and weakens transcriptional recovery. |
| EP300 | 94.25 | activate or support | acetyltransferase | BioGRID,STRING | Acetyltransferase activity can restore transcriptional competence to p53-responsive programs. |
| HDAC1 | 93.75 | inhibit | deacetylase | BioGRID,STRING | Chromatin and p53 deacetylation can suppress mutant p53 reactivation programs. |
| CREBBP | 93.25 | activate or support | acetyltransferase | BioGRID,STRING | Supports p53-dependent transcription through acetylation and co-activation functions. |
| HIPK2 | 92.61 | activate or support | activating kinase | BioGRID,STRING | HIPK2 promotes activating p53 phosphorylation and apoptotic gene expression. |
| KAT5 | 92.21 | activate or support | acetyltransferase | BioGRID,STRING | TIP60/KAT5-mediated acetylation is linked to p53 activation and apoptotic recovery. |
| USP7 | 91.74 | inhibit | deubiquitinase axis | BioGRID,STRING | Can stabilize the MDM2 axis and indirectly restrain p53 reactivation. |
| ATM | 91.03 | activate or support | dna damage kinase | BioGRID,STRING | DNA-damage signaling can reactivate p53 pathway output through phosphorylation and checkpoint control. |
Train accuracy 0.8446, test loss 0.3758. Detailed dashboard: n/a
Train accuracy 0.8512, test loss 0.3881. Detailed dashboard: tp53_random_forest_metrics.html
Train accuracy 0.9080, test loss 0.3503. Detailed dashboard: tp53_xgboost_metrics.html
Train accuracy 0.8996, test loss 0.3640. Detailed dashboard: tp53_ensemble_metrics.html
| Model | Test Acc | Bal Acc | Precision | Recall | Specificity | F1 | TP/TN/FP/FN |
|---|---|---|---|---|---|---|---|
| GCN | 0.8714 | 0.8365 | 0.7651 | 0.7600 | 0.9129 | 0.7625 | 114/367/35/36 |
| RANDOM_FOREST | 0.8228 | 0.7974 | 0.6628 | 0.7403 | 0.8546 | 0.6994 | 114/341/58/40 |
| XGBOOST | 0.8427 | 0.8172 | 0.7006 | 0.7597 | 0.8747 | 0.7290 | 117/349/50/37 |
| ENSEMBLE | 0.8644 | 0.8023 | 0.8160 | 0.6623 | 0.9424 | 0.7312 | 102/376/23/52 |
These are unseen test-split examples from ENSEMBLE. Use them as a reviewer-friendly case study to explain why the model is making sensible calls protein by protein.
Downloadable CSV: tp53_ensemble_demo_predictions.csv
| Protein | True Label | Predicted | Probability | Outcome | Direct BioGRID | BioGRID Degree | Distance to TP53 | Experiment Diversity |
|---|---|---|---|---|---|---|---|---|
| RPA1 | STRING-supported | STRING-supported | 0.8344 | Correct | 1 | 1145 | 1 | 13 |
| ESR1 | STRING-supported | STRING-supported | 0.8348 | Correct | 1 | 878 | 1 | 13 |
| ESR2 | STRING-supported | STRING-supported | 0.9812 | Correct | 0 | 706 | 2 | 8 |
| HDAC1 | STRING-supported | STRING-supported | 0.8818 | Correct | 1 | 508 | 1 | 14 |
| USP7 | STRING-supported | STRING-supported | 0.9115 | Correct | 1 | 401 | 1 | 14 |
| LARP7 | BioGRID-only | BioGRID-only | 0.6027 | Correct | 1 | 485 | 1 | 9 |
| UFL1 | BioGRID-only | BioGRID-only | 0.4446 | Correct | 1 | 479 | 1 | 9 |
| CUL3 | BioGRID-only | STRING-supported | 0.8015 | Mismatch | 1 | 998 | 1 | 13 |
| EFTUD2 | BioGRID-only | STRING-supported | 0.6453 | Mismatch | 1 | 668 | 1 | 12 |
| RBM39 | BioGRID-only | STRING-supported | 0.7846 | Mismatch | 1 | 513 | 1 | 14 |
Upload one of the prepared one-row CSV files from your local computer. The page will validate it against the saved ENSEMBLE held-out examples and show the prediction immediately. In this dataset, negative samples mean BioGRID-only (not STRING-supported).
Use one of the files below. This static browser demo validates prepared held-out samples one at a time.
Recommended files to demonstrate correct negative predictions: S06_ufl1.csv and S07_mepce.csv.