P73

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Tumor protein p73
File:PBB Protein TP73 image.jpg PDB rendering based on 1cok.
Identifiers
Symbols	TP73 ; P73
External IDs	Template:OMIM5 Template:MGI HomoloGene: 3960
Gene ontology Molecular function Template:GNF GO Template:GNF GO Template:GNF GO Template:GNF GO Cellular component Template:GNF GO Biological process Template:GNF GO Template:GNF GO Template:GNF GO Template:GNF GO Template:GNF GO Template:GNF GO Template:GNF GO Template:GNF GO Template:GNF GO
RNA expression pattern
File:PBB GE TP73 220804 s at tn.png
More reference expression data
Orthologs
Template:GNF Ortholog box
Species	Human	Mouse
Entrez	n/a	n/a
Ensembl	n/a	n/a
UniProt	n/a	n/a
RefSeq (mRNA)	n/a	n/a
RefSeq (protein)	n/a	n/a
Location (UCSC)	n/a	n/a
PubMed search	n/a	n/a

WikiDoc Resources for P73
Articles
Most recent articles on P73 Most cited articles on P73 Review articles on P73 Articles on P73 in N Eng J Med, Lancet, BMJ
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Powerpoint slides on P73 Images of P73 Photos of P73 Podcasts & MP3s on P73 Videos on P73
Evidence Based Medicine
Cochrane Collaboration on P73 Bandolier on P73 TRIP on P73
Clinical Trials
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US National Guidelines Clearinghouse on P73 NICE Guidance on P73 NHS PRODIGY Guidance FDA on P73 CDC on P73
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Definitions
Definitions of P73
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Experimental / Informatics
List of terms related to P73

Overview

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 which is 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 counter part, 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 which cause cellular transformations have also been found to result in increased p73 expression. Furthermore, recent finding are suggesting that deregulated over expression of transcription factors within the body involved in cell cycle regulation and synthesis of DNA in mammalian cells (i.e.: E2F-1), induces the expression of p73. Many researchers believe that these results are beginning to suggest that p73 may not be a tumor suppressor but rather an oncoprotien. 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 being over expressed and ultimately plays a role in tumorigenesis.

Genes of the p53 family are known to be complex. The viral oncoproteins (i.e.: Adenovirus 1EB) which efficiently inhibit p53 function, are unable to inactivate p73 and those which 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.

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)

Further reading

• Kaghad, M., H. Bonnet, A. Yang, L. Creancier, J. C. Biscan, A. Valent, A. Minty, P. Chalon, J. M. Lelias, X. Dumont, P. Ferrara, F. McKeon, and D. Caput. 1997. Monoallelically expressed gene related to p53 at 1p36, a region frequently deleted in neuroblastoma and other human cancers. Cell 90:809-819. Template:Entrez Pubmed
• Levrero M, De Laurenzi V, Costanzo A, Gong J, Wang JY, Melino G. (2000). J. Cell Sci., 113: (10). 1661-1670 Template:Entrez Pubmed
• Pozniak, C. D., S. Radinovic, A. Yang, F. McKeon, D. R. Kaplan, and F. D. Miller. 2000. An anti-apoptotic role for the p53 family member, p73, during developmental neuron death. Science 289:304-306 Template:Entrez Pubmed
• Yang, A., N. Walker, R. Bronson, M. Kaghad, M. Oosterwegel, J. Bonnin, C. Vagner, H. Bonnet, P. Dikkes, A. Scharpe, F. McKeon, and D. Caput. 2000. p73-deficient mice have neurological, pheromonal and inflammatory defects but lack spontaneous tumours. Nature 404:99-103. Template:Entrez Pubmed
• Kaelin WG (1999). "The emerging p53 gene family". J. Natl. Cancer Inst. 91 (7): 594–8. PMID 10203277.
• Davis PK, Dowdy SF (2001). "p73". Int. J. Biochem. Cell Biol. 33 (10): 935–9. PMID 11470228.
• Salomoni P, Pandolfi PP (2002). "The role of PML in tumor suppression". Cell. 108 (2): 165–70. PMID 11832207.
• Melino G (2004). "p73, the "assistant" guardian of the genome?". Ann. N. Y. Acad. Sci. 1010: 9–15. 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.CS1 maint: Multiple names: authors list (link)
• 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.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• 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.CS1 maint: Multiple names: authors list (link)
• 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.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• 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.CS1 maint: Multiple names: authors list (link)