Atlas of Genetics and Cytogenetics in Oncology and Haematology


Home   Genes   Leukemias   Solid Tumours   Cancer-Prone   Deep Insight   Case Reports   Journals  Portal   Teaching   

X Y 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 NA

TP53 (Tumor protein p53 (Li-Fraumeni syndrome))

Identity

Other namesP53 (Protein 53 kDa)
HGNC (Hugo) TP53
LocusID (NCBI) 7157
Location 17p13.1
Location_base_pair Starts at 7571720 and ends at 7590868 bp from pter ( according to hg19-Feb_2009)  [Mapping]
 
  Probe(s) - Courtesy Mariano Rocchi, Resources for Molecular Cytogenetics

DNA/RNA

Description The gene encompasses 20 kb of DNA; 11 exons (the first is non-coding).
Transcription 3.0 kb mRNA; 1179 bp open reading frame.

Protein

Description 393 amino acids; 53 kDa protein; numerous post translational modifications: phosphorylation, acetylation, ubiquitination, sumoylation, neddylation. Contains from N-term to C-term, a transactivation domain ((1-42), a Proline rich domain (63-97), a specific DNA binding domain (102-292), 3 nuclear localization signals (305-322), a tetramerization domain that include a nuclear export signal (325-355) and a negative regulatory domain (360-393).
Expression Widely expressed
Localisation Nucleus
Function Tumour suppressor gene. P53 is a transcription factor present at minute level in any normal cells. Upon various types of stress (DNA damage, hypoxia, nucleotide pool depletion, viral infection, oncogene activation), postranslational modification lead to p53 stabilisation and activation. Although the number of genes activated by p53 is rather large, the outcome of p53 activation is either cell cycle arrest in G1 (by p21 ), in G2 (by 14-3-3 s) or apoptosis (by BAX, PUMA or NOXA). The cell growth arrest activity of p53 allows the activation of the DNA repair system of the cell.
Homology The five domains are highly-conserved regions between species (from human to fly). Two new genes homologous to p53 have been discovered, p73 localized at 1p36 and p63 localized at 3q27.

Mutations

Germinal In Li-Fraumeni syndrome, a dominantly inherited disease in which affected individuals are predisposed to develop sarcomas, osteosarcomas, leukemias and breast cancers at unusually early ages. Inherited TP53 mutations are associated with Li-Fraumeni and Li-Fraumeni-like syndromes, characterized by a familial clustering of tumors, with a predominance of soft tissue and bone sarcomas, breast cancers, brain tumors, and adrenocortical carcinomas, diagnosed before the age of 45 years.
Somatic P53 is mutated in about 50% of human cancers, and the non-mutated allele is generally lost. The frequency and the type of mutation may vary from one tumour type to another. Somatic TP53 mutations are frequent in most human cancers, ranging from 5% to 80% depending on the type, stage and etiology of tumors. Most mutations are missense (75%) and other include non-sense (7.5%), deletions, insertions or splicing mutations (17.5%). There are some hot-spots for mutations at CpG dinucleotides at codon positions 175, 248, 273 and 282. TP53 gene mutation is a marker of bad prognosis in a number of cancers, such as breast cancer. Specific mutation spectra are observed in lung, liver and skin cancer that are related to specific carcinogen exposure (tobacco smoke, aflatoxin and UV respectively).

Implicated in

Entity Li-Fraumeni syndrome (LFS)
Disease Autosomal dominant condition, cancer prone disease, Li-Fraumeni syndrome (LFS) is defined by the existence of a proband with early onset sarcoma and a first degree relative with cancer before 45 years, plus another first/second degree relative with cancer at before 45 years or sarcoma at any age. Clinical definitions for Li-Fraumeni like syndromes (LFL) have also been proposed by Eeles and Birch. Germline mutation of TP53 is found in about 70% of LFS and 50% of LFL cases. In a few cases of LFS/LFL families free of TP53 mutations, germline mutations in genes connected to the p53 pathway have been found: CHK2, PTEN, CDKN2A.
Prognosis Most common cancer in Li-Fraumeni children (before the age of 10 years) are: soft tissues sarcoma, brain tumors and adrenocortical carcinomas; osteosarcoma predominate in adolescents; afterwards, female breast cancer, soft tissue sarcomas and brain tumors prevail, and other less frequent cancers such as leukaemias or colon carcinomas are also observed. Multiple primary cancers are quite characteristic of Li- Fraumeni syndrome but may also be representative of Bloom's syndrome. Cancers in this disease, as in other cancer-prone diseases, often occur early in life: 50% of patients aged 30 years have had a cancer (i.e. penetrance is 50%, according to this disease definition), and penetrance is 90% at age 60 years.
Oncogenesis (known) germinal mutations are variable, but are mostly missense mutations located in exons 4 to 10. In tumours occurring in these patients, the other (wild-type) allele is often lost, in accordance with the two-hit model for neoplasia.
  
Entity Haematological malignancies
Oncogenesis TP53 gene alterations have been found in:
- 20 - 30% of blast crisis CML (mostly in the myeloid type), often associated with i(17q).
- 5% of MDS cases and 15% of ANLL often with a visible del(17p).
- 2% of ALL (but with high variations according to the ALL type, reaching 50% of L3 ALL (and Burkitt lymphomas).
- 15% of CLL (and 40% in the aggressive CLL transformation into the Richter's syndrome) and 30% of adult T-cell leukaemia (only found in the aggressive form).
- 5-10% of multiple myelomas.
- 60-80% of Hodgkin disease.
- 30% of high grade B-cell NHL (rare in low grade NHL), and 50% of HIV-related NHL.
TP53 gene alterations in haematological malignancies are associated with a poor prognosis.
  
Entity Skin cancers
Disease Skin cancers include basal cell carcinomas, squamous cell cercinomas, and melanomas.
Prognosis Highly different according to the pathological group.
Oncogenesis TP53 is mutated in 40% of basal cell carcinomas and squamous cell carcinomas while mutations are infrequent in malignant melanoma. The pattern of TP53 mutation in skin cancer is highly related to UV exposure with a high frequency of CC->TT and C->T transitions and specific hotspots at codons 196 and 278.
  
Entity Melanoma
Disease Melanoma is a malignant tumor of melanocytes. Epidemiologic evidence suggests that exposure to ultraviolet (UV) radiation and the sensitivity of an individual's skin to UV radiation are risk factors for skin cancer including melanoma.
Oncogenesis TP53 gene mutations are rare in melanoma. They often lose Apaf-1, a cell-death effector that acts with cytochrome c and caspase-9 to mediate p53-dependent apoptosis. It may contribute to the low frequency of TP53 mutations observed in this highly chemoresistant tumour type.
  
Entity Breast cancer
Oncogenesis TP53 is mutated in 25% of breast cancers with hotspots at codons 175, 220, 245, 248, 273. Geographical variations in mutation patterns have been observed. The prevalence of mutations is higher in large size, high grade and estrogen receptor negative tumors. It is also higher in BRCA1-related tumors. TP53 mutation is a factor of poor prognosis independently of tumor stage and hormone receptor content. It is associated with poor response to doxorubicin therapy.
  
Entity Head and neck squamous cell carcinoma
Disease Head and neck cancer is an important health problem around the world accounting for approximately 500 000 new cases each year. The carcinogenesis of head and neck results from a dysregulation of cellular proliferation, differentiation and cell death. The major etiologic agents are tobacco and alcohol consumption and for some cases human papilloma virus (HPV) infection.
Oncogenesis TP53 mutation can be found in about 40-60% of HNSCC cancers and is thought to be an early event as it is often detected in precancerous lesions. TP53 mutation is associated with poor prognosis in HNSCC.
  
Entity Lung cancers
Disease Lung cancers are neuroendocrine lung tumours (small cell lung carcinomas, carcinoids, large cell neuroendocrine carcinomas) or non neuroendocrine lung tumours (squamous carcinomas, adenocarcinomas, large cell carcinomas).
Oncogenesis Is multistep, through C-MYC or N-MYC activation, H-RAS1 or K-RAS2 mutation, P53, RB1, and P16 inactivation, loss of heterozygosity (LOH) at 3p, 13q, 17p. TP53 is mutated in 40% of lung cancers with frequent G->T transversions at codons 157, 158, 245, 248, 249 and 273. These mutations are linked to exposure to tobacco smoke. TP53 gene mutations may be associated with bad prognosis.
  
Entity Oesophagus cancers
Disease Two main forms: squamous cell carcinoma and adenocarcinoma
Oncogenesis TP53 is mutated in 45% of oesophageal cancers with hotspots at codons 175, 176, 248, 273, 282. It is thought to be an early event as it is often detected in precancerous lesions.
  
Entity Liver cancer
Cytogenetics Losses of 1p, 4q, 5p, 5q, 8q, 13q, 16p, 16q, and 17p in 20 to 50% of cases.
Oncogenesis Specific mutation at codon 249 related to aflatoxin B1 dietary exposure in exposed area (China, Africa); low frequency of mutation in developed countries.
  
Entity Gastric cancer
Disease Risk factors for gastric cancer include: Helicobacter pylori gastric infection, advanced age, male gender, diet including dry salted foods, atrophic gastritis, pernicious anemia, cigarette smoking, Menetrier's disease , and familial polyposis. Adenocarcinoma histology accounts for 90% to 95% of all gastric malignancies. The prognosis of patients with gastric cancer is related to tumor extent and includes both nodal involvement and direct tumor extension beyond the gastric wall. Tumor grade may also provide some prognostic information.
Oncogenesis TP53 mutations are found in about 30% of gastric cancer with a spectrum similar to the one of colorectal cancer. The prognostic value of these mutations is unknown.
  
Entity Colorectal cancers
Disease There are two types of colorectal cancers, according to the ploidy:
- The diploid form, RER+ (Replication Error+), sporadic, without loss of heterozygosity (LOH), with few mutations of p53 and APC, and right-sided.
-The polyploid form, RER-, with LOH (5q, 17p, 18q), mutations in p53, and more often left-sided, they have a worse prognosis.
Prognosis Survival, although improving, is not much more than 50% after 5 years.
Cytogenetics Diploid tumours without frequent allelic losses; aneuploid tumours with numerous allelic losses; LOH on chromosomes 17 and 18 in more than 75% of cases; other chromosome arms losses in about 50% of cases.
Oncogenesis A number of genes are known to be implicated in tumour progression in colorectal cancers : APC, P53, KRAS2, mismatch repair genes (MMR genes). TP53 is mutated in 45% of colorectal cancer cases with a majority of C->T transitions at CpG sites and hotspots at codons 175, 245, 248, 273 and 282. TP53 mutation may be associated with poor prognosis in patient treated with chemotherapy.
  
Entity Bladder cancer
Prognosis Highly variable, according to the stage and the grade.
Cytogenetics -9, -11 or del(11p), del(17p) and LOH at 17p, del(13q), frequent other LOH, aneuploidy, polyploidy, complex karyotypes.
Oncogenesis Multi-step and largely unknown process; loss of 9q and P53 mutations would be early events; RB1, and P16 inactivation, EGFR overexpression, LOH at 3p, 8p, 11p, 13q, 17p, 18q. TP53 is mutated in 30% of bladder cancers with a majority of G->A transitions at non-CpG sites and 2 hotspots at codons 280 and 285.
  
Entity Cervical cancer
Disease Risk factors for cervical cancer include predominantly infection with certain human papillomaviruses such as HPV16 and HPV18. Carcinoma of the uterine cervix is one of the most common neoplasias among women worldwide.
Oncogenesis The frequency of TP53 mutation in cervical cancer is very low. The p53 pathway is inactivated by the E6 protein that binds and inactivates the p53 protein. Rare TP53 mutations have been detected in HPV negative cancer.
  
Entity Ovary carcinoma
Disease Epithelial carcinoma of the ovary is one of the most common gynecologic malignancies. The most important risk factor for ovarian cancer is a family history of a first-degree relative (mother, daughter, or sister) with the disease.
Oncogenesis TP53 mutation is present in 20% in early stage to 80% in late stage ovarian cancers. The prognostic value of TP53 gene mutation is still a matter of debate, although positive IHC staining for p53 protein seems to be associated with poor prognosis.
  
Entity Prostate cancer
Oncogenesis TP53 mutations are found in less than 20% of prostate cancers with a main hotspot at codon 273. Little is known about the role and prognostic value of these mutations.
  
Entity Glioblastoma
Disease Glioblastoma is the most malignant astrocytic tumor and is preferentially located in the cerebral hemisphere. It may develop from a less malignant precursor lesion such as diffuse astrocytoma or anaplastic astrocytoma, or may develop de novo (secondary glioblastoma and primary glioblastoma respectively). Secondary glioblastoma are more frequent in younger patients and have a better prognosis.
Oncogenesis TP53 mutation is an early and frequent (over 60%) event in secondary glioblastomas while it is rare in primary glioblastomas (inferior to 10%) with hotspots at codons 175, 248 and 273. TP53 mutation is associated with good prognosis as it is more frequent in secondary glioblastomas which occur in young patients and are of better prognosis.
  

To be noted

Germinal mutations of P53 have also been found in families where the criteria for LFS or LFL were not reached.

Other Leukemias implicated (Data extracted from papers in the Atlas)

Leukemias 11q23ChildAMLID1615 11q23ID1030 11q23secondLeukID1131 t1119ELLID1029 t0812q24q22ID2057
t0814ID1050 8p11inMPDID1091 inv8p11q13ID1189 PrimarCutanALCLID2118 t0708q34p11ID1409
t0809p12q33ID1129 t0811p11p15ID1200 t0811p12p15ID1521 t0812p12p11ID1330 t0812p12q15ID1201
t0817p12q23ID1387 t0817p12q25ID1202 t0819p11q13ID1315 t0819p12q13ID1203 t0822p11q11ID1224
t0822p11q13ID1119 t0921q34q22ID1483 t68ID1090 t813ID1094 t68ID1090
t813ID1094 TcellClassifID2079 12pmyeloID1032

Other Solid tumors implicated (Data extracted from papers in the Atlas)

Solid Tumors AmeloblastomID5945 MedulloblastomaID5065 rhab5004 rhabID5004 blad5001
bladID5001 colon5006 colonID5006 EmbryoRhabdomyoID5193 IrisHamartomaID5100
OvaryEpithTumID5230 rhab5004 rhabID5004 SkinMelanomID5416 ConvOsteoID5344
OvarianGermCellID5067 AlvRhabdomyosarcID5194 blad5001 bladID5001 rhab5004
rhabID5004 SalivGlandOverviewID5328 softissuTumID5042 AstrocytID5007 BoneTumorID5143
ConvOsteoID5344 LaryngealOverviewID5087 liposarc5029 liposarcID5029 OsteoblastomaID5343
OsteosarcID5043 OvarianTumOverviewID5231 PenileTumorID5278 RetinoblastomID5008 SalivGlandOverviewID5328
t1122q24q12RhabdoID6285 WellDiffLiposarcomaID5167 LymphangioLeiomyoID5135

External links

Nomenclature
HGNC (Hugo)TP53   11998
Cards
AtlasP53ID88
Entrez_Gene (NCBI)TP53  7157  tumor protein p53
GeneCards (Weizmann)TP53
Ensembl hg19 (Hinxton)ENSG00000141510 [Gene_View]  chr17:7571720-7590868 [Contig_View]  TP53 [Vega]
Ensembl hg38 (Hinxton)ENSG00000141510 [Gene_View]  chr17:7571720-7590868 [Contig_View]  TP53 [Vega]
ICGC DataPortalENSG00000141510
cBioPortalTP53
AceView (NCBI)TP53
Genatlas (Paris)TP53
WikiGenes7157
SOURCE (Princeton)TP53
Genomic and cartography
GoldenPath hg19 (UCSC)TP53  -     chr17:7571720-7590868 -  17p13.1   [Description]    (hg19-Feb_2009)
GoldenPath hg38 (UCSC)TP53  -     17p13.1   [Description]    (hg38-Dec_2013)
EnsemblTP53 - 17p13.1 [CytoView hg19]  TP53 - 17p13.1 [CytoView hg38]
Mapping of homologs : NCBITP53 [Mapview hg19]  TP53 [Mapview hg38]
OMIM114480   114500   114550   137800   151623   191170   202300   259500   260350   260500   607107   614740   
Gene and transcription
Genbank (Entrez)AB082923 AF052180 AF307851 AK223026 AK225838
RefSeq transcript (Entrez)NM_000546 NM_001126112 NM_001126113 NM_001126114 NM_001126115 NM_001126116 NM_001126117 NM_001126118 NM_001276695 NM_001276696 NM_001276697 NM_001276698 NM_001276699 NM_001276760 NM_001276761
RefSeq genomic (Entrez)AC_000149 NC_000017 NC_018928 NG_017013 NT_010718 NW_001838403 NW_004929405
Consensus coding sequences : CCDS (NCBI)TP53
Cluster EST : UnigeneHs.740601 [ NCBI ]
CGAP (NCI)Hs.740601
Alternative Splicing : Fast-db (Paris)GSHG0013057
Alternative Splicing GalleryENSG00000141510
Gene ExpressionTP53 [ NCBI-GEO ]     TP53 [ SEEK ]   TP53 [ MEM ]
SOURCE (Princeton)Expression in : [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
Protein : pattern, domain, 3D structure
UniProt/SwissProtP04637 (Uniprot)
NextProtP04637  [Medical]
With graphics : InterProP04637
Splice isoforms : SwissVarP04637 (Swissvar)
Domaine pattern : Prosite (Expaxy)P53 (PS00348)   
Domains : Interpro (EBI)p53-like_TF_DNA-bd    p53/RUNT-type_TF_DNA-bd    p53_DNA-bd    p53_tetrameristn    p53_transactivation_domain    p53_tumour_suppressor   
Related proteins : CluSTrP04637
Domain families : Pfam (Sanger)P53 (PF00870)    P53_TAD (PF08563)    P53_tetramer (PF07710)   
Domain families : Pfam (NCBI)pfam00870    pfam08563    pfam07710   
DMDM Disease mutations7157
Blocks (Seattle)P04637
PDB (SRS)1A1U    1AIE    1C26    1DT7    1GZH    1H26    1HS5    1JSP    1KZY    1MA3    1OLG    1OLH    1PES    1PET    1SAE    1SAF    1SAK    1SAL    1TSR    1TUP    1UOL    1XQH    1YC5    1YCQ    1YCR    1YCS    2AC0    2ADY    2AHI    2ATA    2B3G    2BIM    2BIN    2BIO    2BIP    2BIQ    2F1X    2FEJ    2FOJ    2FOO    2GS0    2H1L    2H2D    2H2F    2H4F    2H4H    2H4J    2H59    2J0Z    2J10    2J11    2J1W    2J1X    2J1Y    2J1Z    2J20    2J21    2K8F    2L14    2LY4    2OCJ    2PCX    2VUK    2WGX    2X0U    2X0V    2X0W    2XWR    2YBG    2YDR    2Z5S    2Z5T    3D05    3D06    3D07    3D08    3D09    3D0A    3DAB    3DAC    3IGK    3IGL    3KMD    3KZ8    3LW1    3OQ5    3PDH    3Q01    3Q05    3Q06    3SAK    3TG5    3TS8    3ZME    4AGL    4AGM    4AGN    4AGO    4AGP    4AGQ    4BUZ    4BV2    4HFZ    4HJE    4IBQ    4IBS    4IBT    4IBU    4IBV    4IBW    4IBY    4IBZ    4IJT    4KVP    4LO9    4LOE    4LOF    4MZI    4MZR   
PDB (PDBSum)1A1U    1AIE    1C26    1DT7    1GZH    1H26    1HS5    1JSP    1KZY    1MA3    1OLG    1OLH    1PES    1PET    1SAE    1SAF    1SAK    1SAL    1TSR    1TUP    1UOL    1XQH    1YC5    1YCQ    1YCR    1YCS    2AC0    2ADY    2AHI    2ATA    2B3G    2BIM    2BIN    2BIO    2BIP    2BIQ    2F1X    2FEJ    2FOJ    2FOO    2GS0    2H1L    2H2D    2H2F    2H4F    2H4H    2H4J    2H59    2J0Z    2J10    2J11    2J1W    2J1X    2J1Y    2J1Z    2J20    2J21    2K8F    2L14    2LY4    2OCJ    2PCX    2VUK    2WGX    2X0U    2X0V    2X0W    2XWR    2YBG    2YDR    2Z5S    2Z5T    3D05    3D06    3D07    3D08    3D09    3D0A    3DAB    3DAC    3IGK    3IGL    3KMD    3KZ8    3LW1    3OQ5    3PDH    3Q01    3Q05    3Q06    3SAK    3TG5    3TS8    3ZME    4AGL    4AGM    4AGN    4AGO    4AGP    4AGQ    4BUZ    4BV2    4HFZ    4HJE    4IBQ    4IBS    4IBT    4IBU    4IBV    4IBW    4IBY    4IBZ    4IJT    4KVP    4LO9    4LOE    4LOF    4MZI    4MZR   
PDB (IMB)1A1U    1AIE    1C26    1DT7    1GZH    1H26    1HS5    1JSP    1KZY    1MA3    1OLG    1OLH    1PES    1PET    1SAE    1SAF    1SAK    1SAL    1TSR    1TUP    1UOL    1XQH    1YC5    1YCQ    1YCR    1YCS    2AC0    2ADY    2AHI    2ATA    2B3G    2BIM    2BIN    2BIO    2BIP    2BIQ    2F1X    2FEJ    2FOJ    2FOO    2GS0    2H1L    2H2D    2H2F    2H4F    2H4H    2H4J    2H59    2J0Z    2J10    2J11    2J1W    2J1X    2J1Y    2J1Z    2J20    2J21    2K8F    2L14    2LY4    2OCJ    2PCX    2VUK    2WGX    2X0U    2X0V    2X0W    2XWR    2YBG    2YDR    2Z5S    2Z5T    3D05    3D06    3D07    3D08    3D09    3D0A    3DAB    3DAC    3IGK    3IGL    3KMD    3KZ8    3LW1    3OQ5    3PDH    3Q01    3Q05    3Q06    3SAK    3TG5    3TS8    3ZME    4AGL    4AGM    4AGN    4AGO    4AGP    4AGQ    4BUZ    4BV2    4HFZ    4HJE    4IBQ    4IBS    4IBT    4IBU    4IBV    4IBW    4IBY    4IBZ    4IJT    4KVP    4LO9    4LOE    4LOF    4MZI    4MZR   
PDB (RSDB)1A1U    1AIE    1C26    1DT7    1GZH    1H26    1HS5    1JSP    1KZY    1MA3    1OLG    1OLH    1PES    1PET    1SAE    1SAF    1SAK    1SAL    1TSR    1TUP    1UOL    1XQH    1YC5    1YCQ    1YCR    1YCS    2AC0    2ADY    2AHI    2ATA    2B3G    2BIM    2BIN    2BIO    2BIP    2BIQ    2F1X    2FEJ    2FOJ    2FOO    2GS0    2H1L    2H2D    2H2F    2H4F    2H4H    2H4J    2H59    2J0Z    2J10    2J11    2J1W    2J1X    2J1Y    2J1Z    2J20    2J21    2K8F    2L14    2LY4    2OCJ    2PCX    2VUK    2WGX    2X0U    2X0V    2X0W    2XWR    2YBG    2YDR    2Z5S    2Z5T    3D05    3D06    3D07    3D08    3D09    3D0A    3DAB    3DAC    3IGK    3IGL    3KMD    3KZ8    3LW1    3OQ5    3PDH    3Q01    3Q05    3Q06    3SAK    3TG5    3TS8    3ZME    4AGL    4AGM    4AGN    4AGO    4AGP    4AGQ    4BUZ    4BV2    4HFZ    4HJE    4IBQ    4IBS    4IBT    4IBU    4IBV    4IBW    4IBY    4IBZ    4IJT    4KVP    4LO9    4LOE    4LOF    4MZI    4MZR   
Human Protein AtlasENSG00000141510
Peptide AtlasP04637
HPRD01859
IPIIPI00025087   IPI00375319   IPI00973801   IPI01009016   IPI01009039   IPI01008713   IPI00796188   IPI00894418   IPI00895905   IPI01018116   IPI00902894   IPI00965012   IPI00816804   IPI01011775   IPI00967077   IPI00968201   
Protein Interaction databases
DIP (DOE-UCLA)P04637
IntAct (EBI)P04637
FunCoupENSG00000141510
BioGRIDTP53
IntegromeDBTP53
STRING (EMBL)TP53
Ontologies - Pathways
QuickGOP04637
Ontology : AmiGOprotein import into nucleus, translocation  negative regulation of transcription from RNA polymerase II promoter  negative regulation of transcription from RNA polymerase II promoter  negative regulation of transcription from RNA polymerase II promoter  DNA strand renaturation  chromatin  nuclear chromatin  RNA polymerase II core promoter sequence-specific DNA binding  RNA polymerase II core promoter proximal region sequence-specific DNA binding transcription factor activity involved in positive regulation of transcription  RNA polymerase II transcription factor binding  RNA polymerase II transcription regulatory region sequence-specific DNA binding transcription factor activity involved in positive regulation of transcription  in utero embryonic development  somitogenesis  release of cytochrome c from mitochondria  protease binding  p53 binding  T cell proliferation involved in immune response  B cell lineage commitment  T cell lineage commitment  response to ischemia  DNA binding  chromatin binding  damaged DNA binding  sequence-specific DNA binding transcription factor activity  copper ion binding  protein binding  ATP binding  nucleus  nucleoplasm  nucleoplasm  replication fork  transcription factor TFIID complex  nucleolus  cytoplasm  mitochondrion  mitochondrial matrix  endoplasmic reticulum  cytosol  cytosol  base-excision repair  nucleotide-excision repair  double-strand break repair  regulation of transcription, DNA-templated  protein complex assembly  apoptotic process  cellular response to DNA damage stimulus  DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest  DNA damage response, signal transduction by p53 class mediator resulting in transcription of p21 class mediator  ER overload response  cell cycle arrest  cell cycle arrest  transforming growth factor beta receptor signaling pathway  Notch signaling pathway  Ras protein signal transduction  multicellular organismal development  gastrulation  negative regulation of neuroblast proliferation  central nervous system development  cell aging  blood coagulation  protein localization  transcription factor binding  negative regulation of DNA replication  zinc ion binding  cell proliferation  negative regulation of cell proliferation  determination of adult lifespan  rRNA transcription  response to salt stress  response to X-ray  response to gamma radiation  positive regulation of cardiac muscle cell apoptotic process  viral process  nuclear matrix  nuclear body  PML body  enzyme binding  protein kinase binding  protein phosphatase binding  cell differentiation  negative regulation of cell growth  DNA damage response, signal transduction by p53 class mediator  DNA damage response, signal transduction by p53 class mediator  negative regulation of transforming growth factor beta receptor signaling pathway  receptor tyrosine kinase binding  positive regulation of histone deacetylation  chromatin assembly  mitotic G1 DNA damage checkpoint  ubiquitin protein ligase binding  positive regulation of protein oligomerization  T cell differentiation in thymus  regulation of tissue remodeling  cellular protein localization  cellular response to UV  histone deacetylase regulator activity  histone acetyltransferase binding  multicellular organism growth  cellular response to drug  cellular response to glucose starvation  intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator  identical protein binding  regulation of apoptotic process  positive regulation of apoptotic process  negative regulation of apoptotic process  negative regulation of apoptotic process  protein complex  positive regulation of neuron apoptotic process  transcription regulatory region DNA binding  negative regulation of transcription, DNA-templated  positive regulation of transcription, DNA-templated  positive regulation of transcription, DNA-templated  positive regulation of transcription from RNA polymerase II promoter  positive regulation of transcription from RNA polymerase II promoter  positive regulation of transcription from RNA polymerase II promoter  response to antibiotic  regulation of mitochondrial membrane permeability  protein heterodimerization activity  protein N-terminus binding  negative regulation of fibroblast proliferation  embryonic organ development  positive regulation of peptidyl-tyrosine phosphorylation  chaperone binding  negative regulation of helicase activity  protein tetramerization  neuron apoptotic process  protein phosphatase 2A binding  positive regulation of thymocyte apoptotic process  positive regulation of cell cycle arrest  cellular response to hypoxia  cellular response to ionizing radiation  mitotic cell cycle arrest  intrinsic apoptotic signaling pathway by p53 class mediator  positive regulation of release of cytochrome c from mitochondria  positive regulation of cell aging  replicative senescence  oxidative stress-induced premature senescence  intrinsic apoptotic signaling pathway  oligodendrocyte apoptotic process  MDM2/MDM4 family protein binding  positive regulation of protein insertion into mitochondrial membrane involved in apoptotic signaling pathway  negative regulation of macromitophagy  regulation of mitochondrial membrane permeability involved in apoptotic process  negative regulation of reactive oxygen species metabolic process  positive regulation of reactive oxygen species metabolic process  positive regulation of intrinsic apoptotic signaling pathway  
Ontology : EGO-EBIprotein import into nucleus, translocation  negative regulation of transcription from RNA polymerase II promoter  negative regulation of transcription from RNA polymerase II promoter  negative regulation of transcription from RNA polymerase II promoter  DNA strand renaturation  chromatin  nuclear chromatin  RNA polymerase II core promoter sequence-specific DNA binding  RNA polymerase II core promoter proximal region sequence-specific DNA binding transcription factor activity involved in positive regulation of transcription  RNA polymerase II transcription factor binding  RNA polymerase II transcription regulatory region sequence-specific DNA binding transcription factor activity involved in positive regulation of transcription  in utero embryonic development  somitogenesis  release of cytochrome c from mitochondria  protease binding  p53 binding  T cell proliferation involved in immune response  B cell lineage commitment  T cell lineage commitment  response to ischemia  DNA binding  chromatin binding  damaged DNA binding  sequence-specific DNA binding transcription factor activity  copper ion binding  protein binding  ATP binding  nucleus  nucleoplasm  nucleoplasm  replication fork  transcription factor TFIID complex  nucleolus  cytoplasm  mitochondrion  mitochondrial matrix  endoplasmic reticulum  cytosol  cytosol  base-excision repair  nucleotide-excision repair  double-strand break repair  regulation of transcription, DNA-templated  protein complex assembly  apoptotic process  cellular response to DNA damage stimulus  DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest  DNA damage response, signal transduction by p53 class mediator resulting in transcription of p21 class mediator  ER overload response  cell cycle arrest  cell cycle arrest  transforming growth factor beta receptor signaling pathway  Notch signaling pathway  Ras protein signal transduction  multicellular organismal development  gastrulation  negative regulation of neuroblast proliferation  central nervous system development  cell aging  blood coagulation  protein localization  transcription factor binding  negative regulation of DNA replication  zinc ion binding  cell proliferation  negative regulation of cell proliferation  determination of adult lifespan  rRNA transcription  response to salt stress  response to X-ray  response to gamma radiation  positive regulation of cardiac muscle cell apoptotic process  viral process  nuclear matrix  nuclear body  PML body  enzyme binding  protein kinase binding  protein phosphatase binding  cell differentiation  negative regulation of cell growth  DNA damage response, signal transduction by p53 class mediator  DNA damage response, signal transduction by p53 class mediator  negative regulation of transforming growth factor beta receptor signaling pathway  receptor tyrosine kinase binding  positive regulation of histone deacetylation  chromatin assembly  mitotic G1 DNA damage checkpoint  ubiquitin protein ligase binding  positive regulation of protein oligomerization  T cell differentiation in thymus  regulation of tissue remodeling  cellular protein localization  cellular response to UV  histone deacetylase regulator activity  histone acetyltransferase binding  multicellular organism growth  cellular response to drug  cellular response to glucose starvation  intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator  identical protein binding  regulation of apoptotic process  positive regulation of apoptotic process  negative regulation of apoptotic process  negative regulation of apoptotic process  protein complex  positive regulation of neuron apoptotic process  transcription regulatory region DNA binding  negative regulation of transcription, DNA-templated  positive regulation of transcription, DNA-templated  positive regulation of transcription, DNA-templated  positive regulation of transcription from RNA polymerase II promoter  positive regulation of transcription from RNA polymerase II promoter  positive regulation of transcription from RNA polymerase II promoter  response to antibiotic  regulation of mitochondrial membrane permeability  protein heterodimerization activity  protein N-terminus binding  negative regulation of fibroblast proliferation  embryonic organ development  positive regulation of peptidyl-tyrosine phosphorylation  chaperone binding  negative regulation of helicase activity  protein tetramerization  neuron apoptotic process  protein phosphatase 2A binding  positive regulation of thymocyte apoptotic process  positive regulation of cell cycle arrest  cellular response to hypoxia  cellular response to ionizing radiation  mitotic cell cycle arrest  intrinsic apoptotic signaling pathway by p53 class mediator  positive regulation of release of cytochrome c from mitochondria  positive regulation of cell aging  replicative senescence  oxidative stress-induced premature senescence  intrinsic apoptotic signaling pathway  oligodendrocyte apoptotic process  MDM2/MDM4 family protein binding  positive regulation of protein insertion into mitochondrial membrane involved in apoptotic signaling pathway  negative regulation of macromitophagy  regulation of mitochondrial membrane permeability involved in apoptotic process  negative regulation of reactive oxygen species metabolic process  positive regulation of reactive oxygen species metabolic process  positive regulation of intrinsic apoptotic signaling pathway  
Pathways : BIOCARTAATM Signaling Pathway [Genes]    Telomeres, Telomerase, Cellular Aging, and Immortality [Genes]    Hypoxia and p53 in the Cardiovascular system [Genes]    Regulation of transcriptional activity by PML [Genes]    BTG family proteins and cell cycle regulation [Genes]    RB Tumor Suppressor/Checkpoint Signaling in response to DNA damage [Genes]    Double Stranded RNA Induced Gene Expression [Genes]    Overview of telomerase protein component gene hTert Transcriptional Regulation [Genes]    Chaperones modulate interferon Signaling Pathway [Genes]    Apoptotic Signaling in Response to DNA Damage [Genes]    Regulation of cell cycle progression by Plk3 [Genes]    CTCF: First Multivalent Nuclear Factor [Genes]    Estrogen-responsive protein Efp controls cell cycle and breast tumors growth [Genes]    Role of BRCA1, BRCA2 and ATR in Cancer Susceptibility [Genes]    Cell Cycle: G1/S Check Point [Genes]    Tumor Suppressor Arf Inhibits Ribosomal Biogenesis [Genes]    Cell Cycle: G2/M Checkpoint [Genes]    p53 Signaling Pathway [Genes]   
Pathways : KEGGMAPK signaling pathway    Cell cycle    p53 signaling pathway    PI3K-Akt signaling pathway    Apoptosis    Wnt signaling pathway    Neurotrophin signaling pathway    Thyroid hormone signaling pathway    Amyotrophic lateral sclerosis (ALS)    Huntington's disease    Hepatitis C    Hepatitis B    Measles    HTLV-I infection    Herpes simplex infection    Epstein-Barr virus infection    Pathways in cancer    Transcriptional misregulation in cancer    Viral carcinogenesis    Proteoglycans in cancer    MicroRNAs in cancer    Colorectal cancer    Pancreatic cancer    Endometrial cancer    Glioma    Prostate cancer    Thyroid cancer    Basal cell carcinoma    Melanoma    Bladder cancer    Chronic myeloid leukemia    Small cell lung cancer    Non-small cell lung cancer   
REACTOMEP04637 [protein]
REACTOME PathwaysREACT_578 Apoptosis [pathway]
REACTOME PathwaysREACT_115566 Cell Cycle [pathway]
REACTOME PathwaysREACT_120956 Cellular responses to stress [pathway]
REACTOME PathwaysREACT_604 Hemostasis [pathway]
REACTOME PathwaysREACT_111102 Signal Transduction [pathway]
Protein Interaction DatabaseTP53
DoCM (Curated mutations)TP53
Wikipedia pathwaysTP53
Gene fusion - rearrangements
Polymorphisms : SNP, variants
NCBI Variation ViewerTP53 [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)TP53
dbVarTP53
ClinVarTP53
1000_GenomesTP53 
Exome Variant ServerTP53
SNP (GeneSNP Utah)TP53
SNP : HGBaseTP53
Genetic variants : HAPMAPTP53
Genomic VariantsTP53  TP53 [DGVbeta]
Mutations
ICGC Data PortalENSG00000141510 
Cancer Gene: CensusTP53 
Somatic Mutations in Cancer : COSMICTP53 
CONAN: Copy Number AnalysisTP53 
LOVD (Leiden Open Variation Database)Whole genome datasets
LOVD (Leiden Open Variation Database)LOVD - Leiden Open Variation Database
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
LOVD (Leiden Open Variation Database)MSeqDR-LSDB Mitochondrial Disease Locus Specific Database
Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] 
Diseases
DECIPHER (Syndromes)17:7571720-7590868
Mutations and Diseases : HGMDTP53
OMIM114480    114500    114550    137800    151623    191170    202300    259500    260350    260500    607107    614740   
MedgenTP53
NextProtP04637 [Medical]
GENETestsTP53
Disease Genetic AssociationTP53
Huge Navigator TP53 [HugePedia]  TP53 [HugeCancerGEM]
snp3D : Map Gene to Disease7157
DGIdb (Drug Gene Interaction db)TP53
General knowledge
Homologs : HomoloGeneTP53
Homology/Alignments : Family Browser (UCSC)TP53
Phylogenetic Trees/Animal Genes : TreeFamTP53
Chemical/Protein Interactions : CTD7157
Chemical/Pharm GKB GenePA36679
Drug Sensitivity TP53
Clinical trialTP53
Cancer Resource (Charite)ENSG00000141510
Other databases
Other databasehttp://www-p53.iarc.fr/
Other databasehttp://p53.bii.a-star.edu.sg/index.php
Other databasehttp://p53.free.fr/p53_Info/p53_Info.html
Other databasehttp://www.lf2.cuni.cz/projects/germline_mut_p53.htm
Other databasehttp://cancergenome.broadinstitute.org/index.php?tgene=TP53
Probes
Litterature
PubMed499 Pubmed reference(s) in Entrez
CoreMineTP53
GoPubMedTP53
iHOPTP53

Bibliography

Li-Fraumeni syndrome--a molecular and clinical review.
Varley JM, Evans DG, Birch JM
British journal of cancer. 1997 ; 76 (1) : 1-14.
PMID 9218725
 
Dial 9-1-1 for p53: mechanisms of p53 activation by cellular stress.
Ljungman M
Neoplasia (New York, N.Y.). 2000 ; 2 (3) : 208-225.
PMID 10935507
 
Surfing the p53 network.
Vogelstein B, Lane D, Levine AJ
Nature. 2000 ; 408 (6810) : 307-310.
PMID 11099028
 
p53: death star.
Vousden KH
Cell. 2000 ; 103 (5) : 691-694.
PMID 11114324
 
P63 and P73: P53 mimics, menaces and more.
Yang A, McKeon F
Nature reviews. Molecular cell biology. 2000 ; 1 (3) : 199-207.
PMID 11252895
 
Assessing TP53 status in human tumours to evaluate clinical outcome.
Soussi T, Bˆ©roud C
Nature reviews. Cancer. 2001 ; 1 (3) : 233-240.
PMID 11902578
 
The evolution of diverse biological responses to DNA damage: insights from yeast and p53.
Wahl GM, Carr AM
Nature cell biology. 2001 ; 3 (12) : E277-E286.
PMID 11781586
 
p73: Friend or foe in tumorigenesis.
Melino G, De Laurenzi V, Vousden KH
Nature reviews. Cancer. 2002 ; 2 (8) : 605-615.
PMID 12154353
 
Li-Fraumeni and related syndromes: correlation between tumor type, family structure, and TP53 genotype.
Olivier M, Goldgar DE, Sodha N, Ohgaki H, Kleihues P, Hainaut P, Eeles RA
Cancer research. 2003 ; 63 (20) : 6643-6650.
PMID 14583457
 
Focus on the p53 gene and cancer: advances in TP53 mutation research.
Soussi T
Human mutation. 2003 ; 21 (3) : 173-175.
PMID 12619102
 
25 Years of p53 Research
Pierre Hainaut and Klas G Wiman
Eds..
 
The p53 pathway: positive and negative feedback loops.
Harris SL, Levine AJ
Oncogene. 2005 ; 24 (17) : 2899-2908.
PMID 15838523
 
Transcription-independent pro-apoptotic functions of p53.
Moll UM, Wolff S, Speidel D, Deppert W
Current opinion in cell biology. 2005 ; 17 (6) : 631-636.
PMID 16226451
 
p53 aerobics: the major tumor suppressor fuels your workout.
Kruse JP, Gu W
Cell metabolism. 2006 ; 4 (1) : 1-3.
PMID 16814724
 
p53: more research and more questions.
Braithwaite AW, Prives CL
Cell death and differentiation. 2006 ; 13 (6) : 877-880.
PMID 16708075
 
TP53 mutations in human cancers: functional selection and impact on cancer prognosis and outcomes.
Petitjean A, Achatz MI, Borresen-Dale AL, Hainaut P, Olivier M
Oncogene. 2007 ; 26 (15) : 2157-2165.
PMID 17401424
 
Impact of mutant p53 functional properties on TP53 mutation patterns and tumor phenotype: lessons from recent developments in the IARC TP53 database.
Petitjean A, Mathe E, Kato S, Ishioka C, Tavtigian SV, Hainaut P, Olivier M
Human mutation. 2007 ; 28 (6) : 622-629.
PMID 17311302
 
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

Search in all EBI   NCBI

Contributor(s)

Written07-1998Richard Hamelin, Jean-Loup Huret
INSERM U434, Laboratoire de Genetique des Tumeurs, CEPH, Paris (RH), and Genetics, Dept Medical Information, University of Poitiers; CHU Poitiers Hospital, F-86021 Poitiers (JLH), France.
Updated10-1998Richard Hamelin, Jean-Loup Huret
INSERM U434, Laboratoire de Genetique des Tumeurs, CEPH, Paris (RH), and Genetics, Dept Medical Information, University of Poitiers; CHU Poitiers Hospital, F-86021 Poitiers (JLH), France.
Updated12-2001Thierry Soussi
Laboratoire de Genotoxicologie des tumeurs, Institut Curie, Universite Pierre et Marie Curie, 26 rue d'Ulm, 75005 Paris, France.
Updated10-2002Thierry Soussi
Laboratoire de Genotoxicologie des tumeurs, Institut Curie, Universite Pierre et Marie Curie, 26 rue d'Ulm, 75005 Paris, France.
Updated04-2007Magali Olivier
Molecular Carcinogenesis and Biomarkers Group, International Agency for Research on Cancer (IARC/CIRC), 150 Cours Albert Thomas, F-69372 Lyon CEDEX 08, France

Citation

This paper should be referenced as such :
Soussi, T
P53 (protein 53 kDa)
Atlas Genet Cytogenet Oncol Haematol. 2003;7(1):6-9.
Free online version   Free pdf version   [Bibliographic record ]
History of this paper:
Hamelin, R ; Huret, JL. P53 (protein 53 kDa). Atlas Genet Cytogenet Oncol Haematol. 1999;3(1):8-10.
http://documents.irevues.inist.fr/bitstream/2042/37475/1/10-1998-P53ID88.pdf
Soussi, T. P53 (protein 53 kDa). Atlas Genet Cytogenet Oncol Haematol. 2002;6(2):90-92.
http://documents.irevues.inist.fr/bitstream/2042/37831/1/12-2001-P53ID88.pdf
Soussi, T. P53 (protein 53 kDa). Atlas Genet Cytogenet Oncol Haematol. 2003;7(1):6-9.
http://documents.irevues.inist.fr/bitstream/2042/37921/1/10-2002-P53ID88.pdf
Atlas Genet Cytogenet Oncol Haematol. October 2002
http://documents.irevues.inist.fr/bitstream/handle/2042/15937/04-2007-P53ID88.pdf
URL : http://AtlasGeneticsOncology.org/Genes/P53ID88.html

© Atlas of Genetics and Cytogenetics in Oncology and Haematology
indexed on : Sun Dec 21 03:14:37 CET 2014

Home   Genes   Leukemias   Solid Tumours   Cancer-Prone   Deep Insight   Case Reports   Journals  Portal   Teaching   

For comments and suggestions or contributions, please contact us

jlhuret@AtlasGeneticsOncology.org.