TP53 (Homo sapiens)

Description [+]

Synonyms: TP53, P53, LFS1
Species: Metazoa;Bilateria;Deuterostoma;Chordata;Vertebrata;Mammalia;Primates;Hominidae; Homo sapiens
Short gene description: Cellular tumor antigen p53 (Tumor suppressor p53)(Phosphoprotein p53)(Antigen NY-CO-13) [Source:UniProtKB/Swiss-Prot;Acc:P04637]
Family: other
Process: apoptosis,
Pathways: intrinsic pathway, pre-mitochondrial signaling events,
Criteria: manually curated
Curator comment:
Mouse ortholog(s): Trp53
WIKI: TP53-H_sapiens

References [+]

Blinded by the Light: The Growing Complexity of p53.
Vousden KH, Prives C
While the tumor suppressor functions of p53 have long been recognized, the contribution of p53 to numerous other aspects of disease and normal life is only now being appreciated. This burgeoning range of responses to p53 is reflected by an increasing variety of mechanisms through which p53 can function, although the ability to activate transcription remains key to p53's modus operandi. Control of p53's transcriptional activity is crucial for determining which p53 response is activated, a decision we must understand if we are to exploit efficiently the next generation of drugs that selectively activate or inhibit p53. Cell. 2009 May 1;137(3):413-31.

Induction of apoptosis by wild-type p53 in a human colon tumor-derived cell line.
Shaw P, Bovey R, Tardy S, Sahli R, Sordat B, Costa J
A wild-type p53 gene under control of the metallothionein MT-1 promoter was stably transfected into human colon tumor-derived cell line EB. Repeated inductions of the metallothionein wild-type p53 gene with zinc chloride results in progressive detachment of wild-type p53 cells grown on culture dishes. Examination at both the light and electron microscopic level revealed that cells expressing wild-type p53 developed morphological features of apoptosis. DNA from both attached and detached cells was degraded into a ladder of nucleosomal-sized fragments. Expression of wild-type p53 inhibited colony formation in soft agar and tumor formation in nude mice. Furthermore, established tumors in nude mice underwent regression if wild-type p53 expression was subsequently induced. Regressing tumors showed histological features of apoptosis. Thus, regression of these tumors was the result of apoptosis occurring in vivo. Apoptosis may be a normal part of the terminal differentiation program of colonic epithelial cells. Our results suggest that wild-type p53 could play a critical role in this process. Proc Natl Acad Sci U S A. 1992 May 15;89(10):4495-9.

References from Mouse ortholog(s):

Blinded by the Light: The Growing Complexity of p53.
Vousden KH, Prives C
While the tumor suppressor functions of p53 have long been recognized, the contribution of p53 to numerous other aspects of disease and normal life is only now being appreciated. This burgeoning range of responses to p53 is reflected by an increasing variety of mechanisms through which p53 can function, although the ability to activate transcription remains key to p53's modus operandi. Control of p53's transcriptional activity is crucial for determining which p53 response is activated, a decision we must understand if we are to exploit efficiently the next generation of drugs that selectively activate or inhibit p53. Cell. 2009 May 1;137(3):413-31.

Hematopoietic cells from mice deficient in wild-type p53 are more resistant to induction of apoptosis by some agents.
Lotem J, Sachs L
Wild-type p53 is a tumor-suppressor gene that can induce cell death by apoptosis when expressed in myeloid leukemic and some other types of tumor cells. However, the question remained as to what extent wild-type p53 is a mediator of apoptosis in normal cells. We have used mice deficient in wild-type p53 to determine whether induction of apoptosis in hematopoietic cells from these p53 deficient mice is defective. We show here that bone marrow myeloid progenitor cells from p53-deficient mice are more resistant to induction of apoptosis when there was only a low concentration of the viability factors granulocyte-macrophage colony-stimulating factor; interleukins-1 alpha, -3, and -6; or stem cell factor; or when apoptosis was induced in these cells by irradiation or heat shock. The loss of one allele of wild-type p53 was sufficient for increased resistance. The higher resistance to apoptosis in p53-deficient mice was also found in irradiated thymocytes, but not in thymocytes treated with dexamethasone or in mature peritoneal granulocytes. The degree of resistance in irradiated myeloid progenitors and thymocytes showed a dosage effect of the number of wild-type p53 genes. The results show that wild-type p53 is involved in the induction of apoptosis by some agents in normal hematopoietic cells. Loss of wild-type p53 can, therefore, contribute to tumor development by decreasing cell death at low concentrations of viability factors and after exposure to a DNA-damaging agent. The results also show that there are wild-type p53-dependent and -independent pathways of normal cell apoptosis. Blood. 1993 Aug 15;82(4):1092-6.

Structure & Sequence [+]

Pfam domains: (Pfam is a large collection of protein families.)

Source	Domain Name	Start	End
PFAM A	P53_TAD	5	29
PFAM A	P53	95	289
PFAM A	P53_tetramer	318	359

Protein sequence [+]

Structure links:

Prosite motif and domain information: PS00348
Profile motif and domain profile information: PS50099
Interpro domain information: P04637
PFAM domain and domain family information: P04637
Protein 3D structures from PDB: 2GS0 2FOO 2FEJ 2B3G 1YC5 1KZY 1GZH 1A1U 1YCR 1H26 1JSP 1YCS

Evolution [+]

View protein alignment and tree with Jalview:

Explore tree at phylomeDB: Click here.

Homologs list [+]

Name	Relationship	Species
A_aegypti_AAEL007594-PA	orthology	Aedes
A_aegypti_AAEL007595-PA	orthology	Aedes
A_gambiae_AGAP002352-PA	orthology	Anopheles
A_gambiae_AGAP004319-PA	orthology	Anopheles
TP53	orthology	Chimpanzee
Q4H301_CIOIN	orthology	Ciona
Q4H2Z8_CIOIN	orthology	Ciona
P53_BOVIN	orthology	Cow
P53_CANFA	orthology	Dog
p53	orthology	Fly
TP53	orthology	Fugu
TP53	orthology	Gasterosteus
Q9N1F3_9PRIM	orthology	Gorilla
Q29484_HORSE	orthology	Horse
P53_MACMU	orthology	Macaca
P53_ORYLA	orthology	Medaka
Trp53	orthology	Mouse
TP53	orthology	Orangutan
P53_RABIT	orthology	Rabbit
Tp53	orthology	Rat
TP53	orthology	Tetraodon
tp53	orthology	Xenopus
D_rerio_ENSDARP00000051548	orthology	Zebrafish
TP73	paralogy	Chicken
NP_989682.1	paralogy	Chicken
TP73	paralogy	Chimpanzee
TP63	paralogy	Chimpanzee
IPI00690378.2	paralogy	Cow
IPI00700517.4	paralogy	Cow
TP63	paralogy	Dog
Q8WMQ8_CANFA	paralogy	Dog
TP63	paralogy	Fugu
TP73	paralogy	Fugu
TP73	paralogy	Gasterosteus
TP63	paralogy	Gasterosteus
TP63	paralogy	Gorilla
TP73	paralogy	Gorilla
TP73	paralogy	Horse
TP63	paralogy	Horse
TP63	paralogy	Human
TP73	paralogy	Human
TP63	paralogy	Lyzard
TP73	paralogy	Lyzard
TP73	paralogy	Macaca
TP63	paralogy	Macaca
TP73	paralogy	Medaka
TP63	paralogy	Medaka
TP73	paralogy	Monodelphis
TP63	paralogy	Monodelphis
Trp73	paralogy	Mouse
Trp63	paralogy	Mouse
TP73	paralogy	Orangutan
TP63	paralogy	Orangutan
TP73	paralogy	Ornithorhynchus
TP63	paralogy	Ornithorhynchus
TP63	paralogy	Rabbit
Trp63	paralogy	Rat
NP_001102166.1	paralogy	Rat
TP73	paralogy	Tetraodon
TP63	paralogy	Tetraodon
TP73	paralogy	Xenopus
TP73	paralogy	Zebra finch
TP63	paralogy	Zebra finch
tp73l	paralogy	Zebrafish
tp73	paralogy	Zebrafish

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Gene Ontology [+]

GO id	Name	Ontology type	Evidence
GO:0006355	regulation of transcription, DNA-dependent	biological_proccess	IEA
GO:0045449	regulation of transcription	biological_proccess	IEA
GO:0002347	response to tumor cell	biological_proccess	IEA
GO:0030308	negative regulation of cell growth	biological_proccess	IEA
GO:0010552	positive regulation of specific transcription from RNA polymerase II promoter	biological_proccess	IDA
GO:0000060	protein import into nucleus, translocation	biological_proccess	IEA
GO:0001701	in utero embryonic development	biological_proccess	IEA
GO:0001836	release of cytochrome c from mitochondria	biological_proccess	IEA
GO:0002309	T cell proliferation during immune response	biological_proccess	IEA
GO:0002360	T cell lineage commitment	biological_proccess	IEA
GO:0007369	gastrulation	biological_proccess	IEA
GO:0007417	central nervous system development	biological_proccess	IEA
GO:0008156	negative regulation of DNA replication	biological_proccess	IEA
GO:0009792	embryonic development ending in birth or egg hatching	biological_proccess	IEA
GO:0010332	response to gamma radiation	biological_proccess	IEA
GO:0031571	G1 DNA damage checkpoint	biological_proccess	IEA
GO:0034644	cellular response to UV	biological_proccess	IEA
GO:0042493	response to drug	biological_proccess	IEA
GO:0043525	positive regulation of neuron apoptosis	biological_proccess	IEA
GO:0048147	negative regulation of fibroblast proliferation	biological_proccess	IEA
GO:0051453	regulation of intracellular pH	biological_proccess	IEA
GO:0008629	induction of apoptosis by intracellular signals	biological_proccess	TAS
GO:0000122	negative regulation of transcription from RNA polymerase II promoter	biological_proccess	IEA
GO:0002326	B cell lineage commitment	biological_proccess	IEA
GO:0007406	negative regulation of neuroblast proliferation	biological_proccess	IEA
GO:0009651	response to salt stress	biological_proccess	IEA
GO:0033077	T cell differentiation in the thymus	biological_proccess	IEA
GO:0043066	negative regulation of apoptosis	biological_proccess	IEA
GO:0051276	chromosome organization	biological_proccess	IEA
GO:0006983	ER overload response	biological_proccess	IDA
GO:0042149	cellular response to glucose starvation	biological_proccess	IDA
GO:0042771	DNA damage response, signal transduction by p53 class mediator resulting in induction of apoptosis	biological_proccess	IDA
GO:0010165	response to X-ray	biological_proccess	IEA
GO:0007049	cell cycle	biological_proccess	IEA
GO:0044419	interspecies interaction between organisms	biological_proccess	IEA
GO:0007569	cell aging	biological_proccess	IMP
GO:0051262	protein tetramerization	biological_proccess	TAS
GO:0006974	response to DNA damage stimulus	biological_proccess	IEP
GO:0007050	cell cycle arrest	biological_proccess	TAS
GO:0030154	cell differentiation	biological_proccess	TAS
GO:0008283	cell proliferation	biological_proccess	TAS
GO:0006355	regulation of transcription, DNA-dependent	biological_proccess	IDA
GO:0006289	nucleotide-excision repair	biological_proccess	IMP
GO:0006284	base-excision repair	biological_proccess	TAS
GO:0006461	protein complex assembly	biological_proccess	IDA
GO:0008104	protein localization	biological_proccess	IDA
GO:0007275	multicellular organismal development	biological_proccess	IMP
GO:0046902	regulation of mitochondrial membrane permeability	biological_proccess	TAS
GO:0008635	activation of caspase activity by cytochrome c	biological_proccess	IDA
GO:0051097	negative regulation of helicase activity	biological_proccess	TAS
GO:0006302	double-strand break repair	biological_proccess	IEA
GO:0030308	negative regulation of cell growth	biological_proccess	IMP
GO:0006915	apoptosis	biological_proccess	IEA
GO:0045893	positive regulation of transcription, DNA-dependent	biological_proccess	IEA
GO:0045941	positive regulation of transcription	biological_proccess	IEA
GO:0045944	positive regulation of transcription from RNA polymerase II promoter	biological_proccess	IEA
GO:0009303	rRNA transcription	biological_proccess	IEA
GO:0006974	response to DNA damage stimulus	biological_proccess	IEA
GO:0008285	negative regulation of cell proliferation	biological_proccess	IEA
GO:0042127	regulation of cell proliferation	biological_proccess	IEA
GO:0006917	induction of apoptosis	biological_proccess	IEA
GO:0051726	regulation of cell cycle	biological_proccess	IEA
GO:0007569	cell aging	biological_proccess	IEA
GO:0042771	DNA damage response, signal transduction by p53 class mediator resulting in induction of apoptosis	biological_proccess	IEA
GO:0043065	positive regulation of apoptosis	biological_proccess	IEA
GO:0030330	DNA damage response, signal transduction by p53 class mediator	biological_proccess	IEA
GO:0009411	response to UV	biological_proccess	IEA
GO:0043523	regulation of neuron apoptosis	biological_proccess	IEA
GO:0046902	regulation of mitochondrial membrane permeability	biological_proccess	IEA
GO:0003677	DNA binding	mollecular_function	IEA
GO:0003700	transcription factor activity	mollecular_function	IEA
GO:0008270	zinc ion binding	mollecular_function	IEA
GO:0008134	transcription factor binding	mollecular_function	IPI
GO:0010843	promoter binding	mollecular_function	IDA
GO:0003682	chromatin binding	mollecular_function	IDA
GO:0046872	metal ion binding	mollecular_function	IEA
GO:0003700	transcription factor activity	mollecular_function	IDA
GO:0000739	DNA strand annealing activity	mollecular_function	IDA
GO:0005524	ATP binding	mollecular_function	IDA
GO:0008270	zinc ion binding	mollecular_function	TAS
GO:0046982	protein heterodimerization activity	mollecular_function	IPI
GO:0019899	enzyme binding	mollecular_function	IPI
GO:0051087	chaperone binding	mollecular_function	IPI
GO:0047485	protein N-terminus binding	mollecular_function	IPI
GO:0005507	copper ion binding	mollecular_function	IDA
GO:0005515	protein binding	mollecular_function	IEA
GO:0005634	nucleus	cell_component	IEA
GO:0016605	PML body	cell_component	IDA
GO:0005669	transcription factor TFIID complex	cell_component	IDA
GO:0005657	replication fork	cell_component	IEA
GO:0005829	cytosol	cell_component	IEA
GO:0005783	endoplasmic reticulum	cell_component	IEA
GO:0005730	nucleolus	cell_component	IDA
GO:0005634	nucleus	cell_component	IDA
GO:0005654	nucleoplasm	cell_component	IDA
GO:0005626	insoluble fraction	cell_component	IDA
GO:0016363	nuclear matrix	cell_component	IDA
GO:0005737	cytoplasm	cell_component	IDA
GO:0005739	mitochondrion	cell_component	IDA
GO:0005737	cytoplasm	cell_component	IEA

Check GO Evidence Codes here

KEGG Pathways [+]

KEGG report for TP53: 7157

KEGG pathways for TP53:

hsa04010: MAPK signaling pathway (entry, map)

hsa04110: Cell cycle (entry, map)

hsa04115: p53 signaling pathway (entry, map)

hsa04210: Apoptosis (entry, map)

hsa04310: Wnt signaling pathway (entry, map)

hsa05030: Amyotrophic lateral sclerosis (ALS) (entry, map)

hsa05040: Huntington's disease (entry, map)

hsa05210: Colorectal cancer (entry, map)

hsa05212: Pancreatic cancer (entry, map)

hsa05213: Endometrial cancer (entry, map)

hsa05214: Glioma (entry, map)

hsa05215: Prostate cancer (entry, map)

hsa05216: Thyroid cancer (entry, map)

hsa05217: Basal cell carcinoma (entry, map)

hsa05218: Melanoma (entry, map)

hsa05219: Bladder cancer (entry, map)

hsa05220: Chronic myeloid leukemia (entry, map)

hsa05222: Small cell lung cancer (entry, map)

hsa05223: Non-small cell lung cancer (entry, map)

Information from other databases [+]