{
 "gene": "TP53",
 "run_date": "2026-06-10T10:51:55",
 "timeline": {
  "current_model": "TP53 encodes a tetrameric transcription factor (p53) that functions as a tumor suppressor by transactivating target genes involved in cell cycle arrest, apoptosis, DNA repair, senescence, and autophagy; its stability and activity are tightly regulated by Mdm2-mediated ubiquitination and proteasomal degradation, counteracted by deubiquitinases (USP10, USP11), post-translational modifications including phosphorylation (e.g., Ser46 by a p53DINP1-associated kinase, ATM-mediated), acetylation (at K120 by NAT10, at K382 enhanced by ING4/5 via p300), beta-hydroxybutyrylation (at K120/319/370 by CBP, attenuating activity), and sumoylation/neddylation; p53 binds DNA preferentially at nucleosome edges as a pioneer factor; it produces multiple isoforms (e.g., Delta133p53, p53beta) with distinct and sometimes opposing functions including dominant-negative inhibition and promotion of invasion via EMT; in senescence, p53 drives pericentromeric heterochromatin dismantling through downregulation of TRF2; and hotspot missense mutations in its DNA-binding domain cause loss of sequence-specific DNA binding, dominant-negative effects on wild-type p53, and neomorphic gain-of-function activities including altered iron metabolism, enhanced metastasis, and remodeling of the tumor secretome."
 },
 "narrative": {
  "mechanism_profile": {
   "molecular_activity": [
    {
     "term_id": "GO:0140110",
     "term_label": "transcription regulator activity",
     "supporting_discovery_ids": [
      16,
      2,
      12
     ]
    },
    {
     "term_id": "GO:0003677",
     "term_label": "DNA binding",
     "supporting_discovery_ids": [
      7,
      16
     ]
    }
   ],
   "localization": [
    {
     "term_id": "GO:0005634",
     "term_label": "nucleus",
     "supporting_discovery_ids": [
      0,
      1
     ]
    },
    {
     "term_id": "GO:0005829",
     "term_label": "cytosol",
     "supporting_discovery_ids": [
      0
     ]
    },
    {
     "term_id": "GO:0000228",
     "term_label": "nuclear chromosome",
     "supporting_discovery_ids": [
      7,
      11
     ]
    }
   ],
   "pathway": [
    {
     "term_id": "R-HSA-74160",
     "term_label": "Gene expression (Transcription)",
     "supporting_discovery_ids": [
      16,
      2,
      12
     ]
    },
    {
     "term_id": "R-HSA-5357801",
     "term_label": "Programmed Cell Death",
     "supporting_discovery_ids": [
      5,
      4,
      2
     ]
    },
    {
     "term_id": "R-HSA-9612973",
     "term_label": "Autophagy",
     "supporting_discovery_ids": [
      10
     ]
    },
    {
     "term_id": "R-HSA-8953897",
     "term_label": "Cellular responses to stimuli",
     "supporting_discovery_ids": [
      0,
      11
     ]
    },
    {
     "term_id": "R-HSA-4839726",
     "term_label": "Chromatin organization",
     "supporting_discovery_ids": [
      11,
      7
     ]
    },
    {
     "term_id": "R-HSA-1643685",
     "term_label": "Disease",
     "supporting_discovery_ids": [
      15,
      14,
      17
     ]
    }
   ],
   "complexes": [],
   "partners": [
    "MDM2",
    "USP10",
    "USP11",
    "NAT10",
    "EP300",
    "ING4",
    "UBE3A",
    "TRF2"
   ],
   "other_free_text": []
  }
 },
 "prefetch_data": {
  "uniprot": {
   "accession": "P04637",
   "full_name": "Cellular tumor antigen p53"
  }
 },
 "evaluation": {
  "pairwise": "win",
  "faith_supported": 7,
  "faith_total": 7,
  "faith_pct": 100.0
 },
 "cost": {
  "total_usd": 0.199177
 }
}