GenAge entry for TP53 (Homo sapiens)

Entry selected based on evidence directly linking the gene product to ageing in a mammalian model organism

Gene name (HAGRID: 6)

HGNC symbol: TP53
Aliases: p53; LFS1
Common name: tumor protein p53

Potential relevance to the human ageing process

Main reason for selection

Entry selected based on evidence directly linking the gene product to ageing in a mammalian model organism

Description

TP53 is a tumour suppressor involved in cell cycle regulation, apoptosis, and DNA repair [88]. Several lines of evidence from model organisms link TP53 to ageing, in agreement with its DNA damage protection role.

In flies, expression of a dominant-negative version of TP53 extends lifespan [1567]. Mice with a permanently activated form of TP53 display signs of premature ageing starting at about 18 months of age [11], as do mice heterozygous for TP53 that lack BRCA1 [37]. Overexpression of p44 (one of the short isoforms of p53) also causes a progeroid phenotype [1146], including phosphorylation of tau, synaptic deficits, and cognitive decline [3587]. Additionally, levels of p44 increase with age in the mouse brain [3587]. However, increased but regulated TP53 and CDKN2A activity has been found to ameliorate age-associated central nervous system functional decline in mice, acting to maintain the stem cell pool. This regulated TP53 activity provides a mechanism for extended lifespan and also health span in mice [4333].

Human mutations in TP53 have been associated with cancer [92]. People with a polymorphism that decreases the apoptotic potential of TP53 have increased survival despite a higher proportional mortality from cancer [1290]. The myriad of functions and interactions of TP53, as well as the findings from model organisms, make it a possible player in human ageing.

Cytogenetic information

Cytogenetic band: 17p13.1
Location: 7,668,401 bp to 7,687,550 bp
Orientation: Minus strand

Display region using the UCSC Genome Browser (GRCh38/hg38)

Protein information

Gene Ontology

Process:

GO:0000122; negative regulation of transcription from RNA polymerase II promoter
GO:0000733; DNA strand renaturation
GO:0006284; base-excision repair
GO:0006289; nucleotide-excision repair
GO:0006355; regulation of transcription, DNA-templated
GO:0006366; transcription from RNA polymerase II promoter
GO:0006461; protein complex assembly
GO:0006974; cellular response to DNA damage stimulus
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:0006983; ER overload response
GO:0007050; cell cycle arrest
GO:0007265; Ras protein signal transduction
GO:0007275; multicellular organism development
GO:0007569; cell aging
GO:0008104; protein localization
GO:0008283; cell proliferation
GO:0008285; negative regulation of cell proliferation
GO:0008340; determination of adult lifespan
GO:0010165; response to X-ray
GO:0010332; response to gamma radiation
GO:0010628; positive regulation of gene expression
GO:0016032; viral process
GO:0016925; protein sumoylation
GO:0030154; cell differentiation
GO:0030308; negative regulation of cell growth
GO:0030330; DNA damage response, signal transduction by p53 class mediator
GO:0031065; positive regulation of histone deacetylation
GO:0031497; chromatin assembly
GO:0031571; mitotic G1 DNA damage checkpoint
GO:0032461; positive regulation of protein oligomerization
GO:0034644; cellular response to UV
GO:0035690; cellular response to drug
GO:0042149; cellular response to glucose starvation
GO:0042771; intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator
GO:0042981; regulation of apoptotic process
GO:0043065; positive regulation of apoptotic process
GO:0043066; negative regulation of apoptotic process
GO:0043153; entrainment of circadian clock by photoperiod
GO:0043161; proteasome-mediated ubiquitin-dependent protein catabolic process
GO:0043525; positive regulation of neuron apoptotic process
GO:0045892; negative regulation of transcription, DNA-templated
GO:0045893; positive regulation of transcription, DNA-templated
GO:0045944; positive regulation of transcription from RNA polymerase II promoter
GO:0046677; response to antibiotic
GO:0046827; positive regulation of protein export from nucleus
GO:0046902; regulation of mitochondrial membrane permeability
GO:0048147; negative regulation of fibroblast proliferation
GO:0048512; circadian behavior
GO:0050731; positive regulation of peptidyl-tyrosine phosphorylation
GO:0051097; negative regulation of helicase activity
GO:0051262; protein tetramerization
GO:0051974; negative regulation of telomerase activity
GO:0070245; positive regulation of thymocyte apoptotic process
GO:0071158; positive regulation of cell cycle arrest
GO:0071456; cellular response to hypoxia
GO:0071479; cellular response to ionizing radiation
GO:0072332; intrinsic apoptotic signaling pathway by p53 class mediator
GO:0090200; positive regulation of release of cytochrome c from mitochondria
GO:0090399; replicative senescence
GO:0090403; oxidative stress-induced premature senescence
GO:0097193; intrinsic apoptotic signaling pathway
GO:0097252; oligodendrocyte apoptotic process
GO:1900119; positive regulation of execution phase of apoptosis
GO:1900740; positive regulation of protein insertion into mitochondrial membrane involved in apoptotic signaling pathway
GO:1901796; regulation of signal transduction by p53 class mediator
GO:1902749; regulation of cell cycle G2/M phase transition
GO:1990440; positive regulation of transcription from RNA polymerase II promoter in response to endoplasmic reticulum stress
GO:2000379; positive regulation of reactive oxygen species metabolic process
GO:2001244; positive regulation of intrinsic apoptotic signaling pathway

Cellular component:

GO:0000790; nuclear chromatin
GO:0005634; nucleus
GO:0005654; nucleoplasm
GO:0005657; replication fork
GO:0005669; transcription factor TFIID complex
GO:0005730; nucleolus
GO:0005737; cytoplasm
GO:0005739; mitochondrion
GO:0005759; mitochondrial matrix
GO:0005783; endoplasmic reticulum
GO:0005829; cytosol
GO:0016363; nuclear matrix
GO:0016604; nuclear body
GO:0016605; PML body
GO:0043234; protein complex

Function:

GO:0000977; RNA polymerase II regulatory region sequence-specific DNA binding
GO:0000981; RNA polymerase II transcription factor activity, sequence-specific DNA binding
GO:0001046; core promoter sequence-specific DNA 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:0003677; DNA binding
GO:0003682; chromatin binding
GO:0003684; damaged DNA binding
GO:0003690; double-stranded DNA binding
GO:0003700; transcription factor activity, sequence-specific DNA binding
GO:0005507; copper ion binding
GO:0005515; protein binding
GO:0005524; ATP binding
GO:0008134; transcription factor binding
GO:0008270; zinc ion binding
GO:0019899; enzyme binding
GO:0019901; protein kinase binding
GO:0019903; protein phosphatase binding
GO:0030971; receptor tyrosine kinase binding
GO:0031625; ubiquitin protein ligase binding
GO:0035035; histone acetyltransferase binding
GO:0042802; identical protein binding
GO:0043565; sequence-specific DNA binding
GO:0043621; protein self-association
GO:0044212; transcription regulatory region DNA binding
GO:0046982; protein heterodimerization activity
GO:0047485; protein N-terminus binding
GO:0051087; chaperone binding
GO:0051721; protein phosphatase 2A binding

Hide GO terms

Protein interactions and network

Protein-protein interacting partners in GenAge: TP53, TERT, ATM, ERCC2, ERCC8, WRN, LMNA, IGF1R, TXN, HRAS, MYC, EGFR, PRKCD, PLCG2, PARP1, BRCA1, PIN1, PTEN, CREBBP, HIF1A, NCOR1, RPA1, BLM, BCL2, S100B, HSP90AA1, EGR1, ABL1, BRCA2, TOP2A, TOP2B, TOP1, RAD51, UBE2I, ERCC6, STK11, EP300, PML, GSK3B, HTT, EEF2, ERCC3, PRKDC, AR, PCNA, XRCC6, HSPA8, BAX, RB1, FOXO3, UCHL1, SIRT1, HDAC1, HSPA1A, HSPA1B, PCMT1, MAPK8, YWHAZ, PTK2, MAPK14, SP1, MED1, MAPK9, MAPK3, HMGB1, CCNA2, BMI1, EEF1A1, TFAP2A, CREB1, TBP, APEX1, PTGS2, HSPA9, SIN3A, CDK1, TFDP1, HDAC2, MDM2, TAF1, POLA1, RELA, VCP, UBB, SUMO1, H2AFX, NR3C1, APTX, ESR1, NFKBIA, MTOR, CDKN2A, DBN1, PPP1CA, TP63, RAE1, ATR, CSNK1E, STUB1, CHEK2, CDC42, PPARGC1A, SIRT7, TP53BP1, BAK1, TP73, CDKN1A, MIF, IKBKB, SQSTM1, CDK7
STRING interaction network

Retrieve sequences for TP53

Promoter: Promoter
ORF: ORF
CDS: CDS

Homologs in model organisms

Danio rerio: tp53
Mus musculus: Tp53
Rattus norvegicus: Tp53

In other databases

GenAge model organism genes

A homolog of this gene for Mus musculus is present as Trp53

LongevityMap

This gene is present as TP53

CellAge

This gene is present as TP53