p73

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TP73
Protein TP73 PDB 1cok.png
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesTP73, P73, tumor protein p73
External IDsOMIM: 601990 MGI: 1336991 HomoloGene: 3960 GeneCards: TP73
Gene location (Human)
Chromosome 1 (human)
Chr.Chromosome 1 (human)[1]
Chromosome 1 (human)
Genomic location for TP73
Genomic location for TP73
Band1p36.32Start3,652,516 bp[1]
End3,736,201 bp[1]
RNA expression pattern
PBB GE TP73 220804 s at fs.png
More reference expression data
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_001126330
NM_001126331
NM_011642

RefSeq (protein)

NP_001119802
NP_001119803
NP_035772

Location (UCSC)Chr 1: 3.65 – 3.74 MbChr 4: 154.06 – 154.14 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

p73 is a protein related to the p53 tumor protein. Because of its structural resemblance to p53, it has also been considered a tumor suppressor. It is involved in cell cycle regulation, and induction of apoptosis. Like p53, p73 is characterized by the presence of different isoforms of the protein. This is explained by splice variants, and an alternative promoter in the DNA sequence.

p73, also known as tumor protein 73 (TP73), protein was the first identified homologue of the tumor suppressor gene, p53. Like p53, p73 has several variants. It is expressed as distinct forms differing at either at the C- or the N-terminus. Currently, six different C-terminus splicing variants have been found in normal cells. The p73 gene encodes a protein with a significant sequence homology and a functional similarity with the tumor suppressor p53. The over-expression of p73 in cultured cells promotes a growth arrest and/or apoptosis similarly to p53.

The p73 gene has been mapped to a chromosome region (1p36. 2-3) a locus commonly deleted in various tumor entities and human cancers. Similar to p53 the protein product of p73 induces cell cycle arrest or apoptosis, hence its classification as a tumor suppressor. However unlike its counterpart, p73 is infrequently mutated in cancers. Perhaps, even more shocking is the fact that p73 – deficient mice do not show a tumorigenic phenotype. A deficiency of p53 almost certainly leads to unchecked cell proliferation and is noted in 60% of cancers.

Analyses of many tumors typically found in humans including breast and ovarian cancer show a high expression of p73 when compared to normal tissues in corresponding areas. Adenoviruses that cause cellular transformations have also been found to result in increased p73 expression. Furthermore, recent finding are suggesting that over-expression of transcription factors involved in cell cycle regulation and synthesis of DNA in mammalian cells (e.g.: E2F-1) induces the expression of p73. Many researchers believe that these results imply that p73 may not be a tumor suppressor but rather an oncoprotein. Some suggest that the TP73 locus encodes both a tumor suppressor (TAp73) and a putative oncogene (ΔNp73). This is a strong theory and causes much confusion, as it is unknown which of the two p73 variants is over-expressed and ultimately plays a role in tumorigenesis.

Genes of the p53 family are known to be complex. The viral oncoproteins (e.g. Adenovirus E1B) that efficiently inhibit p53 function are unable to inactivate p73, and those that seem to inhibit p73 have no effect on p53.

Debate persists about the exact function of p73. Recently it has been reported that p73 is enriched in the nervous system and that the p73-deficient mice, which do not exhibit an increased susceptibility to spontaneous tumorigenesis, have neurological and immunological defects. These results have been expanded and it has also been shown that p73 is present in early stages of neurological development and neuronal apoptosis by blocking the proapoptotic function of p53. This strongly implicates p73 as playing a large role in cellular differentiation.

References[edit]

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000078900 - Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000029026 - Ensembl, May 2017
  3. ^ "Human PubMed Reference:".
  4. ^ "Mouse PubMed Reference:".

External links[edit]

Further reading[edit]