p73

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.

TP73
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 4GUQ, 1COK, 1DXS, 2KBY, 2MPS, 2WQI, 2WQJ, 2WTT, 2XWC, 3VD0, 3VD1, 3VD2, 4A63, 4G82, 4G83, 4GUO
Identifiers
Aliases	TP73, P73, tumor protein p73
External IDs	OMIM: 601990 MGI: 1336991 HomoloGene: 3960 GeneCards: TP73
Gene location (Human) Chr. Chromosome 1 (human)[1] Band 1p36.32 Start 3,652,516 bp[1] End 3,736,201 bp[1]
Gene location (Mouse) Chr. Chromosome 4 (mouse)[2] Band 4 E2|4 83.79 cM Start 154,056,253 bp[2] End 154,140,208 bp[2]
RNA expression pattern More reference expression data
Gene ontology Molecular function • DNA binding • sequence-specific DNA binding • GO:0001077, GO:0001212, GO:0001213, GO:0001211, GO:0001205 DNA-binding transcription activator activity, RNA polymerase II-specific • transcription factor binding • chromatin binding • metal ion binding • GO:0000980 RNA polymerase II cis-regulatory region sequence-specific DNA binding • damaged DNA binding • GO:0001948 protein binding • identical protein binding • protein kinase binding • p53 binding • GO:0001131, GO:0001151, GO:0001130, GO:0001204 DNA-binding transcription factor activity • MDM2/MDM4 family protein binding • GO:0001200, GO:0001133, GO:0001201 DNA-binding transcription factor activity, RNA polymerase II-specific Cellular component • cytoplasm • Golgi apparatus • intracellular membrane-bounded organelle • transcription factor complex • cell junction • chromatin • cell nucleus • mitochondrion • nucleoplasm • cytosol Biological process • negative regulation of neuron apoptotic process • positive regulation of oligodendrocyte differentiation • intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator • regulation of transcription, DNA-templated • negative regulation of neuron differentiation • kidney development • cellular response to UV • negative regulation of transcription from RNA polymerase II promoter • protein tetramerization • transcription, DNA-templated • cellular response to DNA damage stimulus • activation of MAPK activity • mitotic G1 DNA damage checkpoint • cell cycle arrest • response to organonitrogen compound • intrinsic apoptotic signaling pathway in response to DNA damage • regulation of mitotic cell cycle • positive regulation of apoptotic process • regulation of gene expression • mismatch repair • cell cycle • negative regulation of cardiac muscle cell proliferation • GO:0022415 viral process • negative regulation of JUN kinase activity • response to gamma radiation • response to X-ray • response to drug • positive regulation of transcription from RNA polymerase II promoter • DNA damage response, signal transduction by p53 class mediator resulting in transcription of p21 class mediator • negative regulation of cell proliferation • positive regulation of cell cycle arrest • apoptotic process • regulation of signal transduction by p53 class mediator • transcription from RNA polymerase II promoter • regulation of apoptotic process • positive regulation of protein insertion into mitochondrial membrane involved in apoptotic signaling pathway • positive regulation of transcription, DNA-templated • regulation of hematopoietic stem cell differentiation Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	7161	22062
Ensembl	ENSG00000078900	ENSMUSG00000029026
UniProt	O15350	Q9JJP2
RefSeq (mRNA)	NM_001126240 NM_001126241 NM_001126242 NM_001204184 NM_001204185 NM_001204186 NM_001204187 NM_001204188 NM_001204189 NM_001204190 NM_001204191 NM_001204192 NM_005427	NM_001126330 NM_001126331 NM_011642
RefSeq (protein)	NP_001119712 NP_001119713 NP_001119714 NP_001191113 NP_001191114 NP_001191115 NP_001191116 NP_001191117 NP_001191118 NP_001191119 NP_001191120 NP_001191121 NP_005418	NP_001119802 NP_001119803 NP_035772
Location (UCSC)	Chr 1: 3.65 – 3.74 Mb	Chr 4: 154.06 – 154.14 Mb
PubMed search	[3]	[4]
Wikidata
View/Edit Human View/Edit Mouse

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

1. GRCh38: Ensembl release 89: ENSG00000078900 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000029026 - Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

External links

• A naturally occurring p73 mutation in a p73-p53 double-mutant lung cancer cell line encodes p73α protein with a dominant-negative function
• TP73+protein,+human at the US National Library of Medicine Medical Subject Headings (MeSH)
• Overview of all the structural information available in the PDB for UniProt: O15350 (Tumor protein p73) at the PDBe-KB.

Further reading

• Kaghad M, Bonnet H, Yang A, et al. (August 1997). "Monoallelically expressed gene related to p53 at 1p36, a region frequently deleted in neuroblastoma and other human cancers". Cell. 90 (4): 809–19. doi:10.1016/S0092-8674(00)80540-1. PMID 9288759.
• Levrero M, De Laurenzi V, Costanzo A, Gong J, Wang JY, Melino G (May 2000). "The p53/p63/p73 family of transcription factors: overlapping and distinct functions". J. Cell Sci. 113 (10): 1661–70. PMID 10769197.
• Pozniak CD, Radinovic S, Yang A, McKeon F, Kaplan DR, Miller FD (July 2000). "An anti-apoptotic role for the p53 family member, p73, during developmental neuron death". Science. 289 (5477): 304–6. doi:10.1126/science.289.5477.304. PMID 10894779.
• Yang A, Walker N, Bronson R, et al. (March 2000). "p73-deficient mice have neurological, pheromonal and inflammatory defects but lack spontaneous tumours". Nature. 404 (6773): 99–103. doi:10.1038/35003607. PMID 10716451.
• Kaelin WG (1999). "The emerging p53 gene family". J. Natl. Cancer Inst. 91 (7): 594–8. doi:10.1093/jnci/91.7.594. PMID 10203277.
• Davis PK, Dowdy SF (2001). "p73". Int. J. Biochem. Cell Biol. 33 (10): 935–9. doi:10.1016/S1357-2725(01)00073-5. PMID 11470228.
• Salomoni P, Pandolfi PP (2002). "The role of PML in tumor suppression". Cell. 108 (2): 165–70. doi:10.1016/S0092-8674(02)00626-8. PMID 11832207.
• Melino G (2004). "p73, the "assistant" guardian of the genome?". Ann. N. Y. Acad. Sci. 1010: 9–15. doi:10.1196/annals.1299.002. PMID 15033688.
• Jacobs WB, Walsh GS, Miller FD (2005). "Neuronal survival and p73/p63/p53: a family affair". The Neuroscientist : A Review Journal Bringing Neurobiology, Neurology and Psychiatry. 10 (5): 443–55. doi:10.1177/1073858404263456. PMID 15359011.
• Rossi M, Sayan AE, Terrinoni A, et al. (2005). "Mechanism of induction of apoptosis by p73 and its relevance to neuroblastoma biology". Ann. N. Y. Acad. Sci. 1028: 143–9. doi:10.1196/annals.1322.015. PMID 15650240.
• Dobbelstein M, Strano S, Roth J, Blandino G (2005). "p73-induced apoptosis: a question of compartments and cooperation". Biochem. Biophys. Res. Commun. 331 (3): 688–93. doi:10.1016/j.bbrc.2005.03.155. PMID 15865923.
• Ramadan S, Terrinoni A, Catani MV, et al. (2005). "p73 induces apoptosis by different mechanisms". Biochem. Biophys. Res. Commun. 331 (3): 713–7. doi:10.1016/j.bbrc.2005.03.156. PMID 15865927.
• Harms KL, Chen X (2006). "p19ras brings a new twist to the regulation of p73 by Mdm2". Sci. STKE. 2006 (337): pe24. doi:10.1126/stke.3372006pe24. PMID 16738062.
• Marabese M, Vikhanskaya F, Broggini M (2007). "p73: a chiaroscuro gene in cancer". Eur. J. Cancer. 43 (9): 1361–72. doi:10.1016/j.ejca.2007.01.042. PMID 17428654.
• Levy D, Adamovich Y, Reuven N, Shaul Y (2007). "The Yes-associated protein 1 stabilizes p73 by preventing Itch-mediated ubiquitination of p73". Cell Death and Differentiation. 14 (4): 743–51. doi:10.1038/sj.cdd.4402063. PMID 17110958.