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
And 60 more GO terms
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
And 5 more GO terms
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
And 21 more GO terms
Show all 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
Protein-Protein network diagram for TP53

Retrieve sequences for TP53

Promoter
Promoter
ORF
ORF
CDS
CDS

Homologs in model organisms

Danio rerio
tp53
Mus musculus
Trp53
Rattus norvegicus
LOC100910954

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

Selected references

External links

EPD
HS_TP53
ORF Accession
NM_000546
CDS Accession
NP_000537
OMIM
191170
HPRD
01859
Ensembl
TP53
UniProt/Swiss-Prot
P53_HUMAN
GeneCards
TP53
Entrez Gene
7157
UniGene
654481
GenAtlas
TP53
Internet
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