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Browse TP53

Summary
SymbolTP53
Nametumor protein p53
Aliases p53; LFS1; Li-Fraumeni syndrome; BCC7; TRP53; antigen NY-CO-13; mutant tumor protein 53; p53 tumor suppresso ......
Chromosomal Location17p13.1
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Basic function annotation.
> Subcellular Location, Domain and Function
> Gene Ontology
> KEGG and Reactome Pathway
> Subcellular Location, Domain and Function
 
Subcellular Location Cytoplasm. Nucleus. Nucleus, PML body. Endoplasmic reticulum. Mitochondrion matrix. Note=Interaction with BANP promotes nuclear localization. Recruited into PML bodies together with CHEK2. Translocates to mitochondria upon oxidative stress. Translocates to mitochondria in response to mitomycin C treatment (PubMed:27323408). ; SUBCELLULAR LOCATION: Isoform 1: Nucleus. Cytoplasm. Note=Predominantly nuclear but localizes to the cytoplasm when expressed with isoform 4.; SUBCELLULAR LOCATION: Isoform 2: Nucleus. Cytoplasm. Note=Localized mainly in the nucleus with minor staining in the cytoplasm.; SUBCELLULAR LOCATION: Isoform 3: Nucleus. Cytoplasm. Note=Localized in the nucleus in most cells but found in the cytoplasm in some cells.; SUBCELLULAR LOCATION: Isoform 4: Nucleus. Cytoplasm. Note=Predominantly nuclear but translocates to the cytoplasm following cell stress.; SUBCELLULAR LOCATION: Isoform 7: Nucleus. Cytoplasm. Note=Localized mainly in the nucleus with minor staining in the cytoplasm.; SUBCELLULAR LOCATION: Isoform 8: Nucleus. Cytoplasm. Note=Localized in both nucleus and cytoplasm in most cells. In some cells, forms foci in the nucleus that are different from nucleoli.; SUBCELLULAR LOCATION: Isoform 9: Cytoplasm.
Domain PF00870 P53 DNA-binding domain
PF08563 P53 transactivation motif
PF07710 P53 tetramerisation motif
Function

Acts as a tumor suppressor in many tumor types; induces growth arrest or apoptosis depending on the physiological circumstances and cell type. Involved in cell cycle regulation as a trans-activator that acts to negatively regulate cell division by controlling a set of genes required for this process. One of the activated genes is an inhibitor of cyclin-dependent kinases. Apoptosis induction seems to be mediated either by stimulation of BAX and FAS antigen expression, or by repression of Bcl-2 expression. In cooperation with mitochondrial PPIF is involved in activating oxidative stress-induced necrosis; the function is largely independent of transcription. Induces the transcription of long intergenic non-coding RNA p21 (lincRNA-p21) and lincRNA-Mkln1. LincRNA-p21 participates in TP53-dependent transcriptional repression leading to apoptosis and seem to have to effect on cell-cycle regulation. Implicated in Notch signaling cross-over. Prevents CDK7 kinase activity when associated to CAK complex in response to DNA damage, thus stopping cell cycle progression. Isoform 2 enhances the transactivation activity of isoform 1 from some but not all TP53-inducible promoters. Isoform 4 suppresses transactivation activity and impairs growth suppression mediated by isoform 1. Isoform 7 inhibits isoform 1-mediated apoptosis. Regulates the circadian clock by repressing CLOCK-ARNTL/BMAL1-mediated transcriptional activation of PER2 (PubMed:24051492).

> Gene Ontology
 
Biological Process GO:0000075 cell cycle checkpoint
GO:0000077 DNA damage checkpoint
GO:0000082 G1/S transition of mitotic cell cycle
GO:0000733 DNA strand renaturation
GO:0001558 regulation of cell growth
GO:0001666 response to hypoxia
GO:0001836 release of cytochrome c from mitochondria
GO:0001844 protein insertion into mitochondrial membrane involved in apoptotic signaling pathway
GO:0006284 base-excision repair
GO:0006289 nucleotide-excision repair
GO:0006323 DNA packaging
GO:0006333 chromatin assembly or disassembly
GO:0006476 protein deacetylation
GO:0006611 protein export from nucleus
GO:0006839 mitochondrial transport
GO:0006913 nucleocytoplasmic transport
GO:0006977 DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest
GO:0006978 DNA damage response, signal transduction by p53 class mediator resulting in transcription of p21 class mediator
GO:0006979 response to oxidative stress
GO:0006983 ER overload response
GO:0006984 ER-nucleus signaling pathway
GO:0007006 mitochondrial membrane organization
GO:0007050 cell cycle arrest
GO:0007093 mitotic cell cycle checkpoint
GO:0007265 Ras protein signal transduction
GO:0007346 regulation of mitotic cell cycle
GO:0007568 aging
GO:0007569 cell aging
GO:0007622 rhythmic behavior
GO:0007623 circadian rhythm
GO:0008340 determination of adult lifespan
GO:0008630 intrinsic apoptotic signaling pathway in response to DNA damage
GO:0008637 apoptotic mitochondrial changes
GO:0009267 cellular response to starvation
GO:0009314 response to radiation
GO:0009411 response to UV
GO:0009416 response to light stimulus
GO:0009648 photoperiodism
GO:0009649 entrainment of circadian clock
GO:0009991 response to extracellular stimulus
GO:0010165 response to X-ray
GO:0010212 response to ionizing radiation
GO:0010259 multicellular organism aging
GO:0010332 response to gamma radiation
GO:0010498 proteasomal protein catabolic process
GO:0010821 regulation of mitochondrion organization
GO:0010822 positive regulation of mitochondrion organization
GO:0010948 negative regulation of cell cycle process
GO:0016049 cell growth
GO:0016570 histone modification
GO:0016575 histone deacetylation
GO:0016925 protein sumoylation
GO:0018108 peptidyl-tyrosine phosphorylation
GO:0018205 peptidyl-lysine modification
GO:0018212 peptidyl-tyrosine modification
GO:0030308 negative regulation of cell growth
GO:0030330 DNA damage response, signal transduction by p53 class mediator
GO:0031056 regulation of histone modification
GO:0031058 positive regulation of histone modification
GO:0031063 regulation of histone deacetylation
GO:0031065 positive regulation of histone deacetylation
GO:0031334 positive regulation of protein complex assembly
GO:0031497 chromatin assembly
GO:0031570 DNA integrity checkpoint
GO:0031571 mitotic G1 DNA damage checkpoint
GO:0031667 response to nutrient levels
GO:0031668 cellular response to extracellular stimulus
GO:0031669 cellular response to nutrient levels
GO:0032386 regulation of intracellular transport
GO:0032388 positive regulation of intracellular transport
GO:0032459 regulation of protein oligomerization
GO:0032461 positive regulation of protein oligomerization
GO:0033157 regulation of intracellular protein transport
GO:0034349 glial cell apoptotic process
GO:0034599 cellular response to oxidative stress
GO:0034644 cellular response to UV
GO:0034976 response to endoplasmic reticulum stress
GO:0035601 protein deacylation
GO:0035690 cellular response to drug
GO:0035794 positive regulation of mitochondrial membrane permeability
GO:0036003 positive regulation of transcription from RNA polymerase II promoter in response to stress
GO:0036293 response to decreased oxygen levels
GO:0036294 cellular response to decreased oxygen levels
GO:0042149 cellular response to glucose starvation
GO:0042493 response to drug
GO:0042594 response to starvation
GO:0042752 regulation of circadian rhythm
GO:0042770 signal transduction in response to DNA damage
GO:0042771 intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator
GO:0042772 DNA damage response, signal transduction resulting in transcription
GO:0043153 entrainment of circadian clock by photoperiod
GO:0043161 proteasome-mediated ubiquitin-dependent protein catabolic process
GO:0043254 regulation of protein complex assembly
GO:0043523 regulation of neuron apoptotic process
GO:0043525 positive regulation of neuron apoptotic process
GO:0043618 regulation of transcription from RNA polymerase II promoter in response to stress
GO:0043620 regulation of DNA-templated transcription in response to stress
GO:0044089 positive regulation of cellular component biogenesis
GO:0044770 cell cycle phase transition
GO:0044772 mitotic cell cycle phase transition
GO:0044773 mitotic DNA damage checkpoint
GO:0044774 mitotic DNA integrity checkpoint
GO:0044783 G1 DNA damage checkpoint
GO:0044819 mitotic G1/S transition checkpoint
GO:0044839 cell cycle G2/M phase transition
GO:0044843 cell cycle G1/S phase transition
GO:0045786 negative regulation of cell cycle
GO:0045787 positive regulation of cell cycle
GO:0045926 negative regulation of growth
GO:0045930 negative regulation of mitotic cell cycle
GO:0046677 response to antibiotic
GO:0046822 regulation of nucleocytoplasmic transport
GO:0046824 positive regulation of nucleocytoplasmic transport
GO:0046825 regulation of protein export from nucleus
GO:0046827 positive regulation of protein export from nucleus
GO:0046902 regulation of mitochondrial membrane permeability
GO:0048144 fibroblast proliferation
GO:0048145 regulation of fibroblast proliferation
GO:0048147 negative regulation of fibroblast proliferation
GO:0048511 rhythmic process
GO:0048512 circadian behavior
GO:0050730 regulation of peptidyl-tyrosine phosphorylation
GO:0050731 positive regulation of peptidyl-tyrosine phosphorylation
GO:0051052 regulation of DNA metabolic process
GO:0051053 negative regulation of DNA metabolic process
GO:0051095 regulation of helicase activity
GO:0051097 negative regulation of helicase activity
GO:0051168 nuclear export
GO:0051169 nuclear transport
GO:0051204 protein insertion into mitochondrial membrane
GO:0051205 protein insertion into membrane
GO:0051222 positive regulation of protein transport
GO:0051259 protein oligomerization
GO:0051262 protein tetramerization
GO:0051346 negative regulation of hydrolase activity
GO:0051348 negative regulation of transferase activity
GO:0051402 neuron apoptotic process
GO:0051972 regulation of telomerase activity
GO:0051974 negative regulation of telomerase activity
GO:0070227 lymphocyte apoptotic process
GO:0070228 regulation of lymphocyte apoptotic process
GO:0070230 positive regulation of lymphocyte apoptotic process
GO:0070231 T cell apoptotic process
GO:0070232 regulation of T cell apoptotic process
GO:0070234 positive regulation of T cell apoptotic process
GO:0070242 thymocyte apoptotic process
GO:0070243 regulation of thymocyte apoptotic process
GO:0070245 positive regulation of thymocyte apoptotic process
GO:0070482 response to oxygen levels
GO:0070585 protein localization to mitochondrion
GO:0070997 neuron death
GO:0071103 DNA conformation change
GO:0071156 regulation of cell cycle arrest
GO:0071158 positive regulation of cell cycle arrest
GO:0071214 cellular response to abiotic stimulus
GO:0071216 cellular response to biotic stimulus
GO:0071453 cellular response to oxygen levels
GO:0071456 cellular response to hypoxia
GO:0071478 cellular response to radiation
GO:0071479 cellular response to ionizing radiation
GO:0071482 cellular response to light stimulus
GO:0071496 cellular response to external stimulus
GO:0071887 leukocyte apoptotic process
GO:0071897 DNA biosynthetic process
GO:0072331 signal transduction by p53 class mediator
GO:0072332 intrinsic apoptotic signaling pathway by p53 class mediator
GO:0072395 signal transduction involved in cell cycle checkpoint
GO:0072401 signal transduction involved in DNA integrity checkpoint
GO:0072413 signal transduction involved in mitotic cell cycle checkpoint
GO:0072422 signal transduction involved in DNA damage checkpoint
GO:0072431 signal transduction involved in mitotic G1 DNA damage checkpoint
GO:0072593 reactive oxygen species metabolic process
GO:0072655 establishment of protein localization to mitochondrion
GO:0072657 protein localization to membrane
GO:0090068 positive regulation of cell cycle process
GO:0090150 establishment of protein localization to membrane
GO:0090199 regulation of release of cytochrome c from mitochondria
GO:0090200 positive regulation of release of cytochrome c from mitochondria
GO:0090311 regulation of protein deacetylation
GO:0090312 positive regulation of protein deacetylation
GO:0090316 positive regulation of intracellular protein transport
GO:0090398 cellular senescence
GO:0090399 replicative senescence
GO:0090400 stress-induced premature senescence
GO:0090403 oxidative stress-induced premature senescence
GO:0090559 regulation of membrane permeability
GO:0097193 intrinsic apoptotic signaling pathway
GO:0097194 execution phase of apoptosis
GO:0097252 oligodendrocyte apoptotic process
GO:0097345 mitochondrial outer membrane permeabilization
GO:0098732 macromolecule deacylation
GO:1900117 regulation of execution phase of apoptosis
GO:1900119 positive regulation of execution phase of apoptosis
GO:1900739 regulation of protein insertion into mitochondrial membrane involved in apoptotic signaling pathway
GO:1900740 positive regulation of protein insertion into mitochondrial membrane involved in apoptotic signaling pathway
GO:1901028 regulation of mitochondrial outer membrane permeabilization involved in apoptotic signaling pathway
GO:1901030 positive regulation of mitochondrial outer membrane permeabilization involved in apoptotic signaling pathway
GO:1901214 regulation of neuron death
GO:1901216 positive regulation of neuron death
GO:1901796 regulation of signal transduction by p53 class mediator
GO:1901987 regulation of cell cycle phase transition
GO:1901988 negative regulation of cell cycle phase transition
GO:1901990 regulation of mitotic cell cycle phase transition
GO:1901991 negative regulation of mitotic cell cycle phase transition
GO:1902108 regulation of mitochondrial membrane permeability involved in apoptotic process
GO:1902110 positive regulation of mitochondrial membrane permeability involved in apoptotic process
GO:1902275 regulation of chromatin organization
GO:1902400 intracellular signal transduction involved in G1 DNA damage checkpoint
GO:1902402 signal transduction involved in mitotic DNA damage checkpoint
GO:1902403 signal transduction involved in mitotic DNA integrity checkpoint
GO:1902686 mitochondrial outer membrane permeabilization involved in programmed cell death
GO:1902749 regulation of cell cycle G2/M phase transition
GO:1902806 regulation of cell cycle G1/S phase transition
GO:1902807 negative regulation of cell cycle G1/S phase transition
GO:1903747 regulation of establishment of protein localization to mitochondrion
GO:1903749 positive regulation of establishment of protein localization to mitochondrion
GO:1903829 positive regulation of cellular protein localization
GO:1904951 positive regulation of establishment of protein localization
GO:1905269 positive regulation of chromatin organization
GO:1990440 positive regulation of transcription from RNA polymerase II promoter in response to endoplasmic reticulum stress
GO:2000045 regulation of G1/S transition of mitotic cell cycle
GO:2000106 regulation of leukocyte apoptotic process
GO:2000108 positive regulation of leukocyte apoptotic process
GO:2000134 negative regulation of G1/S transition of mitotic cell cycle
GO:2000278 regulation of DNA biosynthetic process
GO:2000279 negative regulation of DNA biosynthetic process
GO:2000377 regulation of reactive oxygen species metabolic process
GO:2000379 positive regulation of reactive oxygen species metabolic process
GO:2001233 regulation of apoptotic signaling pathway
GO:2001235 positive regulation of apoptotic signaling pathway
GO:2001242 regulation of intrinsic apoptotic signaling pathway
GO:2001244 positive regulation of intrinsic apoptotic signaling pathway
Molecular Function GO:0001046 core promoter sequence-specific DNA binding
GO:0001047 core promoter binding
GO:0001085 RNA polymerase II transcription factor binding
GO:0001228 transcriptional activator activity, RNA polymerase II transcription regulatory region sequence-specific binding
GO:0002020 protease binding
GO:0002039 p53 binding
GO:0003682 chromatin binding
GO:0003684 damaged DNA binding
GO:0005507 copper ion binding
GO:0008134 transcription factor binding
GO:0019902 phosphatase binding
GO:0019903 protein phosphatase binding
GO:0030971 receptor tyrosine kinase binding
GO:0031625 ubiquitin protein ligase binding
GO:0035035 histone acetyltransferase binding
GO:0043621 protein self-association
GO:0044389 ubiquitin-like protein ligase binding
GO:0046982 protein heterodimerization activity
GO:0047485 protein N-terminus binding
GO:0051087 chaperone binding
GO:0051721 protein phosphatase 2A binding
GO:1990782 protein tyrosine kinase binding
Cellular Component GO:0000428 DNA-directed RNA polymerase complex
GO:0000785 chromatin
GO:0000790 nuclear chromatin
GO:0005657 replication fork
GO:0005667 transcription factor complex
GO:0005669 transcription factor TFIID complex
GO:0005759 mitochondrial matrix
GO:0016363 nuclear matrix
GO:0016591 DNA-directed RNA polymerase II, holoenzyme
GO:0016604 nuclear body
GO:0016605 PML body
GO:0030880 RNA polymerase complex
GO:0034399 nuclear periphery
GO:0044454 nuclear chromosome part
GO:0044798 nuclear transcription factor complex
GO:0055029 nuclear DNA-directed RNA polymerase complex
GO:0061695 transferase complex, transferring phosphorus-containing groups
GO:0090575 RNA polymerase II transcription factor complex
> KEGG and Reactome Pathway
 
KEGG hsa04010 MAPK signaling pathway
hsa04071 Sphingolipid signaling pathway
hsa04110 Cell cycle
hsa04115 p53 signaling pathway
hsa04151 PI3K-Akt signaling pathway
hsa04210 Apoptosis
hsa04310 Wnt signaling pathway
hsa04722 Neurotrophin signaling pathway
hsa04919 Thyroid hormone signaling pathway
Reactome R-HSA-114452: Activation of BH3-only proteins
R-HSA-111448: Activation of NOXA and translocation to mitochondria
R-HSA-139915: Activation of PUMA and translocation to mitochondria
R-HSA-1280218: Adaptive Immune System
R-HSA-109581: Apoptosis
R-HSA-390471: Association of TriC/CCT with target proteins during biosynthesis
R-HSA-349425: Autodegradation of the E3 ubiquitin ligase COP1
R-HSA-1640170: Cell Cycle
R-HSA-69620: Cell Cycle Checkpoints
R-HSA-69278: Cell Cycle, Mitotic
R-HSA-2559583: Cellular Senescence
R-HSA-2262752: Cellular responses to stress
R-HSA-390466: Chaperonin-mediated protein folding
R-HSA-1280215: Cytokine Signaling in Immune system
R-HSA-2172127: DAP12 interactions
R-HSA-2424491: DAP12 signaling
R-HSA-2559586: DNA Damage/Telomere Stress Induced Senescence
R-HSA-5693606: DNA Double Strand Break Response
R-HSA-5693532: DNA Double-Strand Break Repair
R-HSA-73894: DNA Repair
R-HSA-5688426: Deubiquitination
R-HSA-186763: Downstream signal transduction
R-HSA-1168372: Downstream signaling events of B Cell Receptor (BCR)
R-HSA-983231: Factors involved in megakaryocyte development and platelet production
R-HSA-2454202: Fc epsilon receptor (FCERI) signaling
R-HSA-2559584: Formation of Senescence-Associated Heterochromatin Foci (SAHF)
R-HSA-69615: G1/S DNA Damage Checkpoints
R-HSA-69481: G2/M Checkpoints
R-HSA-69473: G2/M DNA damage checkpoint
R-HSA-69275: G2/M Transition
R-HSA-180292: GAB1 signalosome
R-HSA-74160: Gene Expression
R-HSA-212436: Generic Transcription Pathway
R-HSA-109582: Hemostasis
R-HSA-168256: Immune System
R-HSA-168249: Innate Immune System
R-HSA-6785807: Interleukin-4 and 13 signaling
R-HSA-109606: Intrinsic Pathway for Apoptosis
R-HSA-392499: Metabolism of proteins
R-HSA-453274: Mitotic G2-G2/M phases
R-HSA-187037: NGF signalling via TRKA from the plasma membrane
R-HSA-2559585: Oncogene Induced Senescence
R-HSA-5689896: Ovarian tumor domain proteases
R-HSA-2559580: Oxidative Stress Induced Senescence
R-HSA-198203: PI3K/AKT activation
R-HSA-6811555: PI5P Regulates TP53 Acetylation
R-HSA-1257604: PIP3 activates AKT signaling
R-HSA-597592: Post-translational protein modification
R-HSA-1912422: Pre-NOTCH Expression and Processing
R-HSA-1912408: Pre-NOTCH Transcription and Translation
R-HSA-5357801: Programmed Cell Death
R-HSA-391251: Protein folding
R-HSA-5693565: Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks
R-HSA-5633007: Regulation of TP53 Activity
R-HSA-6804758: Regulation of TP53 Activity through Acetylation
R-HSA-6804759: Regulation of TP53 Activity through Association with Co-factors
R-HSA-6804760: Regulation of TP53 Activity through Methylation
R-HSA-6804756: Regulation of TP53 Activity through Phosphorylation
R-HSA-6804757: Regulation of TP53 Degradation
R-HSA-6804754: Regulation of TP53 Expression
R-HSA-6806003: Regulation of TP53 Expression and Degradation
R-HSA-2730905: Role of LAT2/NTAL/LAB on calcium mobilization
R-HSA-3108232: SUMO E3 ligases SUMOylate target proteins
R-HSA-2990846: SUMOylation
R-HSA-3232118: SUMOylation of transcription factors
R-HSA-162582: Signal Transduction
R-HSA-177929: Signaling by EGFR
R-HSA-449147: Signaling by Interleukins
R-HSA-157118: Signaling by NOTCH
R-HSA-186797: Signaling by PDGF
R-HSA-1433557: Signaling by SCF-KIT
R-HSA-983705: Signaling by the B Cell Receptor (BCR)
R-HSA-166520: Signalling by NGF
R-HSA-69541: Stabilization of p53
R-HSA-5628897: TP53 Regulates Metabolic Genes
R-HSA-6803207: TP53 Regulates Transcription of Caspase Activators and Caspases
R-HSA-6791312: TP53 Regulates Transcription of Cell Cycle Genes
R-HSA-5633008: TP53 Regulates Transcription of Cell Death Genes
R-HSA-6796648: TP53 Regulates Transcription of DNA Repair Genes
R-HSA-6803211: TP53 Regulates Transcription of Death Receptors and Ligands
R-HSA-6803204: TP53 Regulates Transcription of Genes Involved in Cytochrome C Release
R-HSA-6804116: TP53 Regulates Transcription of Genes Involved in G1 Cell Cycle Arrest
R-HSA-6804114: TP53 Regulates Transcription of Genes Involved in G2 Cell Cycle Arrest
R-HSA-6804115: TP53 regulates transcription of additional cell cycle genes whose exact role in the p53 pathway remain uncertain
R-HSA-6803205: TP53 regulates transcription of several additional cell death genes whose specific roles in p53-dependent apoptosis remain uncertain
R-HSA-8852276: The role of GTSE1 in G2/M progression after G2 checkpoint
R-HSA-69895: Transcriptional activation of cell cycle inhibitor p21
R-HSA-3700989: Transcriptional Regulation by TP53
R-HSA-69560: Transcriptional activation of p53 responsive genes
R-HSA-5689880: Ub-specific processing proteases
R-HSA-69563: p53-Dependent G1 DNA Damage Response
R-HSA-69580: p53-Dependent G1/S DNA damage checkpoint
Summary
SymbolTP53
Nametumor protein p53
Aliases p53; LFS1; Li-Fraumeni syndrome; BCC7; TRP53; antigen NY-CO-13; mutant tumor protein 53; p53 tumor suppresso ......
Chromosomal Location17p13.1
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Literatures that report relations between TP53 and anti-tumor immunity. The specific mechanism were also collected if the literature reports that a gene specifically promotes or inhibits the infiltration or function of T/NK cells.
> Text Mining
 
  Literatures describing the relation between TP53 and anti-tumor immunity in human cancer.
PMID Cancer type Relation to immunity Evidence sentences
28280037MelanomaPromote immunityHence, targeting the p53 pathway in TME can be exploited to reverse immunosuppression and augment therapeutic benefits beyond tumoricidal effects to harness tumor-specific, durable, and systemic antitumor immunity with minimal toxicity.
26577528Non-Small Cell Lung CarcinomaPromote immunity (T cell function)We identified a novel mechanism by which tumor immune evasion is regulated by p53/miR-34/PDL1 axis.
26872698lung adenocarcinomaPromote immunityHere, using lung adenocarcinoma mouse models, including genetic models, we show that autochthonous tumors that lacked T cell infiltration and resisted current treatment options could be successfully sensitized to host antitumor T cell immunity when appropriately selected immunogenic drugs (e.g., oxaliplatin combined with cyclophosphamide for treatment against tumors expressing oncogenic Kras and lacking Trp53) were used.
26355571AIDS-Related Diffuse Large B-cell LymphomaInhibit immunity (T cell function)When we examined the relationship between stromal immune cells and tumor molecular characteristics, stromal FOXP3+ Treg cells were found to be positively associated with tumor expression of p53 and cMYC, and inversely associated with BCL6.
25398437MelanomaPromote immunityHere we show how combining a senescence-inducing inhibitor of the mitotic kinase Aurora A (AURKA) with an MDM2 antagonist activates p53 in senescent tumors harboring wildtype 53. In the model studied, this effect is accompanied proliferation arrest, mitochondrial depolarization, apoptosis and immune clearance of cancer cells by antitumor leukocytes in a manner reliant upon CCL5, CCL1 and CXCL9.
25351767Breast CarcinomaPromote immunityThe association of lymphocytic invasion of ER-negative breast tumors with the retention of wild-type TP53 implies a novel protective connection between TP53 function and tumor immunosurveillance.
27687306Lung adenocarcinomaPromote immunityTumoral PD-L1 was significantly elevated in TP53 mutant LUADs whereas PIK3CA mutant LUADs exhibited markedly down-regulated PD-L1 expression.
27687306Lung adenocarcinomaPromote immunityLUADs with TP53 or KEAP1 mutations displayed relatively increased CD57 and Granzyme B levels indicative of augmented natural killer (NK) cell infiltration.
24583792Malignant Head and Neck NeoplasmPromote immunity (T cell function); essential for immunotherapyPhase I dendritic cell p53 peptide vaccine for head and neck cancer. p53-specific T-cell frequencies were increased postvaccination in 11 of 16 patients (69%), with IFN-γ secretion detected in four of 16 patients.
16467102Small Cell Lung CarcinomaPromote immunity (T cell function); essential for immunotherapyCombination of p53 cancer vaccine with chemotherapy in patients with extensive stage small cell lung cancer. p53-specific T cell responses to vaccination were observed in 57.1% of patients.
19376606Malignant Splenic Neoplasm; Liver Neuroendocrine TumorPromote immunity (T cell function)Administration of alpha-GalCer resulted in generation of p53 peptide-specific cytotoxic T lymphocytes (CTLs) in mice bearing liver CMS4 tumor, aberrantly expressing p53, but not in mice bearing spleen CMS4 tumor.
27466285MelanomaInhibit immunity (T cell function); essential for immunotherapyLack of p53 Augments Antitumor Functions in Cytolytic T Cells. This increased effector function correlated to the improved control of subcutaneously established murine melanoma after adoptive transfer of p53-KO T cells. Pharmacological inhibition of human TCR-transduced T cells using a combination of p53 inhibitors also potentiated the T-cell effector function and improved persistence.
23787049Hepatocellular CarcinomaPromote immunityA new study reveals that p53 also acts through a novel non-cell-autonomous mechanism, by stimulating the innate immune system to maintain tissue homeostasis and suppress tumorigenesis.
17251933Liver CarcinomaPromote immunity (T cell function)We show that even brief reactivation of endogenous p53 in p53-deficient tumours can produce complete tumour regressions. The primary response to p53 was not apoptosis, but instead involved the induction of a cellular senescence program that was associated with differentiation and the upregulation of inflammatory cytokines. This program, although producing only cell cycle arrest in vitro, also triggered an innate immune response that targeted the tumour cells in vivo, thereby contributing to tumour clearance.
24987057Metastatic Gastrointestinal CarcinomaPromote immunity (T cell function); increase the efficacy of immunotherapyFurthermore, the frequency of PD1+ CD8+ T cells showed an inverse correlation with the peak CD8+ p53 response (P=0.02) and antibody blockade of PD1 in vitro increased the p53 immune responses detected after the second or third immunizations.
29672836Colorectal Carcinoma; urothelial carcinoma; urachal adenocarcinomasPromote immunitySequence variations were observed in TP53 (66%), KRAS (21%), BRAF (4%), PIK3CA (4%), FGFR1 (1%), MET (1%), NRAS (1%), and PDGFRA (1%).
29604063colorectal carcinoma； endometrial cancerPromote immunityGenomic instability, which is a hallmark of cancer, is generally thought to occur in the middle to late stages of tumourigenesis, following the acquisition of permissive molecular aberrations such as TP53 mutation or whole genome doubling.
24037725Follicular LymphomaPromote immunityAbnormalities associated with transformation of the disease likely impair immune surveillance, activate the nuclear factor-κB pathway, and deregulate p53 and B-cell transcription factors.
23975435B16 Malignant MelanomaPromote immunityInterestingly, this tumor-promoting effect by p53-deficient MSCs was not observed in non-obese diabetic/severe combined immunodeficiency mice, indicating the immune response has a critical role. Indeed, in the presence of inflammatory cytokines, p53-deficient MSCs expressed more inducible nitric oxide synthase (iNOS) and exhibited greater immunosuppressive capacity. Importantly, tumor promotion by p53-deficient MSCs was abolished by administration of S-methylisothiourea, an iNOS inhibitor.
23935194MelanomaInhibit immunity (T cell function)We also show that the AICD in TCReng CD4 T cells is a death receptor-independent process and that JNK and p53 play critical roles in this process as pharmacological inhibitors targeting JNK activation and p-53-mediated transcription-independent mitochondria-centric death cascade rescued a significant fraction of TCReng CD4 T cells from undergoing AICD without affecting their effector function.
21480325Hepatocellular CarcinomaInhibit immunity (T/NK cell function); immunotherapy targetThe TAAs consisting of cyclophilin B, squamous cell carcinoma antigen recognized by T cells (SART) 2, SART3, p53, multidrug resistance-associated protein (MRP) 3, alpha-fetoprotein (AFP) and human telomerase reverse transcriptase (hTERT) were frequently recognized by T cells and these TAA-derived peptides were capable of generating peptide-specific CTLs in HCC patients, which suggested that these TAAs are immunogenic. Cyclophilin B, SART2, SART3, p53, MRP3, AFP, and hTERT were immunogenic targets for HCC immunotherapy.
19961944T-cell Non-Hodgkin LymphomaPromote immunity (T cell function)In this report we show that, in response to TCR stimulation, T cells from na?ve p53-deficient mice exhibited higher proliferation and drastically reduced apoptosis than WT T cells. CD28 costimulation enhanced the proliferation of TCR-stimulated WT and p53(-/-) T cells, suggesting that p53 uncouples CD28-mediated antiapoptotic and proliferative signals. Unlike WT mice, p53(-/-) mice exhibited a robust tumor-resistant phenotype and developed cytotoxic T-cell responses against OVA. Collectively, these data support the hypothesis that p53 is an essential factor in negative regulation of T-cell responses and have implication for immunomodulation during treatment of cancers and other inflammatory conditions.
24469034Squamous Cell CarcinomaPromote immunityLoss of epithelial p53 and αv integrin cooperate through Akt to induce squamous cell carcinoma yet prevent remodeling of the tumor microenvironment. Here we show that codeletion of the p53 and αv integrin genes in mouse stratified epithelia induced SCCs in 100% of the mice, more frequently and with much shorter latency than deletion of either gene alone.
29793878Metastatic MelanomaPromote immunityTP53 Mutation as Potential Negative Predictor for Response of Anti-CTLA-4 Therapy in Metastatic Melanoma. TP53 mutation was associated with significant poorer progression-free survival (HR, 2.25; 95% CI, 1.15-4.37; P = 0.014), poorer overall survival (HR, 2.05; 95% CI, 1.02-4.13; P = 0.040) and trend of poorer response (OR, 0.20; 95% CI, 0.02-1.62; P = 0.131).
17538933Hepatocellular CarcinomaPromote immunityWe show that even brief reactivation of endogenous p53 in p53-deficient tumours can produce complete tumour regressions. The primary response to p53 was not apoptosis, but instead involved the induction of a cellular senescence program that was associated with differentiation and the upregulation of inflammatory cytokines. This program, although producing only cell cycle arrest in vitro, also triggered an innate immune response that targeted the tumour cells in vivo, thereby contributing to tumour clearance.
23319800MelanomaPromote immunityTrp53 inactivation in the tumor microenvironment promotes tumor progression by expanding the immunosuppressive lymphoid-like stromal network.
16998881Hepatocellular CarcinomaPromote immunityOur results indicate the existence of natural immunosurveillance and tumor immune evasion, involving a T cell response against WT p53 tumor antigen in patients with HCC.
Summary
SymbolTP53
Nametumor protein p53
Aliases p53; LFS1; Li-Fraumeni syndrome; BCC7; TRP53; antigen NY-CO-13; mutant tumor protein 53; p53 tumor suppresso ......
Chromosomal Location17p13.1
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content High-throughput screening data (e.g. CRISPR-Cas9, shRNA and RNAi) for T cell-mediated killing. Genetic screen techniques can identify mechanisms of tumor cell resistance (e.g., PTPN2) and sensitivity (e.g., APLNR) to killing by cytotoxic T cells, the central effectors of anti-tumor immunity. After comprehensively searching, eight groups of screening data sets were collected in the current database. In this tab, users can check whether their selected genes cause resistance or increase sensitivity to T cell-mediated killing in various data sets.
> High-throughput Screening
  Statistical results of TP53 in screening data sets for detecting immune reponses.
PMID Screening System Cancer Type Cell Line Data Set Statistical Results Relation to immunity
29301958CRISPR-Cas9 melanomaB16F10Pmel-1 T cell NA/NSNA/NS
29301958CRISPR-Cas9 melanomaB16F10OT-1 T cell NA/NSNA/NS
28783722CRISPR-Cas9 melanomaMel6242CT-CRISPR NA/NSNA/NS
28723893CRISPR-Cas9 melanomaB16GVAX+Anti-PD1 NA/NSNA/NS
28723893CRISPR-Cas9 melanomaB16GVAX NA/NSNA/NS
25691366RNAiBreast cancerMCF7Luc-CTL assay NA/NSNA/NS
24476824shRNAmelanomaB16Primary screen NA/NSNA/NS
24476824shRNAmelanomaB16Secondary screen NA/NSNA/NS
Summary
SymbolTP53
Nametumor protein p53
Aliases p53; LFS1; Li-Fraumeni syndrome; BCC7; TRP53; antigen NY-CO-13; mutant tumor protein 53; p53 tumor suppresso ......
Chromosomal Location17p13.1
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Transcriptomic and genomic profiling of pre-treated tumor biopsies from responders and non-responders to immunotherapy. These data were used to identify signatures and mechanisms of response to checkpoint blockade (e.g., anti-PDL1 and anti-PD1). One example is that mutations in the gene PBRM1 benefit clinical survival of patients with clear cell renal cell carcinoma. After comprehensively searching, we collected 5 and 6 of transcriptomic and genomic data sets, respectively. In this tab, users can check whether their selected genes have significant difference of expression or mutation between responders and non-responders in various data sets.
> Expression difference between responders and non-responders
> Mutation difference between responders and non-responders
> Expression difference between responders and non-responders
 
Points in the above scatter plot represent the expression difference of TP53 in various data sets.
No PMID Cancer type Group Drug # Res # NRes Log2 (Fold Change) P value Anno
126997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)14120.1860.438
226997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)65-0.2540.902
326997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)870.5020.754
428552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 9160.4770.096
528552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 590.650.727
628552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 470.2610.915
729033130MelanomaallAnti-PD-1 (nivolumab) 2623-0.0380.916
829033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 1511-0.1040.946
929033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 11120.030.986
1029301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 480.130.933
1129301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 2001
1229301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 280.060.979
1329443960Urothelial cancerallAnti-PD-L1 (atezolizumab) 682300.0350.752
> Mutation difference between responders and non-responders
 
Points in the above scatter plot represent the mutation difference of TP53 in various data sets.
No PMID Cancer type Group Drug # Res # NRes % Mut/Res % Mut/NRes % Diff (R vs NR) Pval Anno
125765070Non-small cell lung cancer (NSCLC)allAnti-PD-1 (pembrolizumab) 141757.135.321.80.289
225765070Non-small cell lung cancer (NSCLC)smokingAnti-PD-1 (pembrolizumab) 1037033.336.70.51
325765070Non-small cell lung cancer (NSCLC)non-smokingAnti-PD-1 (pembrolizumab) 4142535.7-10.71
426359337MelanomaallAnti-CTLA-4 (ipilimumab) 2773012.3-12.30.108
526359337MelanomaBRAFiAnti-CTLA-4 (ipilimumab) 0140001
626359337Melanomanon-BRAFiAnti-CTLA-4 (ipilimumab) 2759015.3-15.30.0519
726997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)211714.323.5-9.20.678
826997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)8612.516.7-4.21
926997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)131115.427.3-11.90.63
1028552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 91666.737.529.20.226
1128552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 596044.415.61
1228552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 477528.646.40.242
1329033130MelanomaallAnti-PD-1 (nivolumab) 38275.311.1-5.80.642
1429033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 22134.57.7-3.21
1529033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 16146.214.3-8.10.586
1629301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 111307.7-7.71
1729301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 610001
1829301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 51208.3-8.31
Summary
SymbolTP53
Nametumor protein p53
Aliases p53; LFS1; Li-Fraumeni syndrome; BCC7; TRP53; antigen NY-CO-13; mutant tumor protein 53; p53 tumor suppresso ......
Chromosomal Location17p13.1
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of TP53. The immune-related signatures of 28 TIL types from Charoentong's study, which can be viewed in the download page. For each cancer type, the relative abundance of TILs were inferred by using gene set variation analysis (GSVA) based on gene expression profile. In this tab, users can examine which kinds of TILs might be regulated by the current gene.
> Lymphocyte
 
Summary
SymbolTP53
Nametumor protein p53
Aliases p53; LFS1; Li-Fraumeni syndrome; BCC7; TRP53; antigen NY-CO-13; mutant tumor protein 53; p53 tumor suppresso ......
Chromosomal Location17p13.1
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of TP53. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by TP53.
> Immunoinhibitor
> Immunostimulator
> MHC molecule
> Immunoinhibitor
 
> Immunostimulator
 
> MHC molecule
 
Summary
SymbolTP53
Nametumor protein p53
Aliases p53; LFS1; Li-Fraumeni syndrome; BCC7; TRP53; antigen NY-CO-13; mutant tumor protein 53; p53 tumor suppresso ......
Chromosomal Location17p13.1
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of TP53. In this tab, users can examine which chemokines (or receptors) might be regulated by the current gene.
> Chemokine
> Receptor
> Chemokine
 
> Receptor
 
Summary
SymbolTP53
Nametumor protein p53
Aliases p53; LFS1; Li-Fraumeni syndrome; BCC7; TRP53; antigen NY-CO-13; mutant tumor protein 53; p53 tumor suppresso ......
Chromosomal Location17p13.1
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Distribution of TP53 expression across immune and molecular subtypes.
> Immune subtype
> Molecular subtype
> Immune subtype
 
> Molecular subtype
 
Summary
SymbolTP53
Nametumor protein p53
Aliases p53; LFS1; Li-Fraumeni syndrome; BCC7; TRP53; antigen NY-CO-13; mutant tumor protein 53; p53 tumor suppresso ......
Chromosomal Location17p13.1
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Associations between TP53 and clinical features.
> Overall survival analysis
> Cancer stage
> Tumor grade
> Overall survival
 
> Stage
 
> Grade
 
Summary
SymbolTP53
Nametumor protein p53
Aliases p53; LFS1; Li-Fraumeni syndrome; BCC7; TRP53; antigen NY-CO-13; mutant tumor protein 53; p53 tumor suppresso ......
Chromosomal Location17p13.1
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Drugs targeting TP53 collected from DrugBank database.
> Drugs from DrugBank database
 

  Details on drugs targeting TP53.
ID Name Drug Type Targets #Targets
DB00945Acetylsalicylic acidSmall MoleculeAKR1C1, EDNRA, HSPA5, IKBKB, NFKB1, NFKB2, NFKBIA, PRKAA1, PRKAA2, ......18
DB01593ZincSmall MoleculeA1BG, A2M, AGT, AHSG, ALDOA, APCS, APLP1, APLP2, APOA1, APOA2, APO ......119
DB03347Triethyl PhosphateSmall MoleculeTP531
DB05404AZD 3355Small MoleculeTP531
DB083631-(9-ethyl-9H-carbazol-3-yl)-N-methylmethanamineSmall MoleculeTP531