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Gene Review

TP73  -  tumor protein p73

Homo sapiens

Synonyms: P73, Tumor protein p73, p53-like transcription factor, p53-related protein
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Disease relevance of TP73

  • Therapeutic efficacy of E2F1 in pancreatic cancer correlates with TP73 induction [1].
  • In some tumours, most notably leukaemias and lymphomas, expression of TP73 is reduced, suggesting a tumour suppressor role [2].
  • Importantly, alterations to the proposed regulatory pathway for controlling TP73 isoform expression in colorectal cancer are associated with adverse clinico-pathological characteristics [2].
  • Quantitative TP73 transcript analysis in hepatocellular carcinomas [3].
  • Different expression of P14ARF defines two groups of breast carcinomas in terms of TP73 expression and TP53 mutational status [4].

Psychiatry related information on TP73


High impact information on TP73

  • We propose that the disregulation of p73 contributes to tumorigenesis and that p53-related proteins operate in a network of developmental and cell cycle controls [6].
  • A p53-related gene, p73, which encodes several proteins as a result of alternative splicing, can also induce apoptosis [7].
  • Deregulated expression of DeltaNp73 can bestow oncogenic activity upon the TP73 gene by functionally inactivating the suppressor action of p53 and TAp73 [8].
  • We report that the human TP73 gene generates an NH(2) terminally truncated isoform [8].
  • Maximum synthesis of both proteins is reached by 12 h after mitogen addition when P95 synthesis represents approximately 4%, and P73 approximately 2%, of the total protein synthesis, compared with less than 0.5% for each protein in cells cultured without mitogen [9].

Chemical compound and disease context of TP73


Biological context of TP73

  • In contrast to TP53, tumor-associated overexpression of TP73 in many different cancers, combined with virtual absence of inactivating mutations and lack of a cancer phenotype in the TP73 null mouse are inconsistent with a suppressor function but instead support an oncogenic function [14].
  • These data show that oncogenes can signal to TP73 in vivo [15].
  • Bisulfite genomic sequencing detected aberrant hypermethylation at the 5' region upstream and including the first exon of the TP73 gene in 17 of 44 (39%) oligodendroglial tumors, whereas normal brain tissues showed no methylation in the same region examined [16].
  • The TP73 gene, located on chromosome 1p36.3, encodes a product that shares significant structural homology with the tumor suppressor TP53 [16].
  • In conclusion, our results showed that inactivation of TP73 occurs at the transcriptional level and is associated with promotor hypermethylation [16].

Anatomical context of TP73

  • The analysis of concomitant P14ARF and TP73 overexpression and clinicopathologic parameters of the tumors showed a statistically significant difference with respect to peritumoral vessel invasion (P = 0.01), lymph node metastasis (P = 0.03), negative ERBB2 expression (P = 0.005), and more advanced pathologic stages (P = 0.03) [4].
  • RESULTS: Using a coding-neutral BanI polymorphism in TP73 exon 5 as an allelic marker, we found a pronounced allelic expression bias in one adult brain hippocampus, while 3 other brains (two adult; one fetal) showed approximately equal expression from both alleles [5].
  • Expression of p53-related protein p63 in the gastrointestinal tract and in esophageal metaplastic and neoplastic disorders [17].
  • p63 is a p53-related DNA-binding protein that helps regulate differentiation and proliferation in epithelial progenitor cells [17].
  • Establishment of a cell line with AML1-MTG8, TP53, and TP73 abnormalities from acute myelogenous leukemia [18].

Associations of TP73 with chemical compounds


Physical interactions of TP73


Regulatory relationships of TP73

  • As an alternative, TP73 may be inactivated through aberrant 5' CpG island methylation, a primary mechanism participating in the inactivation of tumor suppressor genes during tumorigenesis [25].
  • The human p63 gene encodes a series of protein isoforms that differ in their N- and/or C-terminal sequences and possess widely varying activities in promoting or repressing p53-related functions and in regulating the proliferation and differentiation of epithelial cells [26].

Other interactions of TP73

  • Despite strong homology, the roles of TP53 and TP73 in tumorigenesis seem to be fundamentally different [14].
  • DFFB maps to 1p36, near the imprinted putative tumour suppressor gene TP73 [27].
  • This aberration seems to occur early in the carcinogenesis process (it is already present in the low-grade forms), although in some instances (DAPK, THBS1, and TP73) it appears also associated with the genesis of anaplastic forms [28].
  • Recent data provide evidence for interacting roles of ZEB1, p300, and a polymorphic 73 bp deletion in intron 1 of the human TP73 gene in this process [2].
  • The genes PLA2G2A (1p35.1-36) and TP73 (1p36.3) were shown to lie outside this consistently lost region, suggesting that neither of them are targets for the 1p loss [29].

Analytical, diagnostic and therapeutic context of TP73


  1. Therapeutic efficacy of E2F1 in pancreatic cancer correlates with TP73 induction. Rödicker, F., Stiewe, T., Zimmermann, S., Pützer, B.M. Cancer Res. (2001) [Pubmed]
  2. Regulating p73 isoforms in human tumours. Coates, P. J. Pathol. (2006) [Pubmed]
  3. Quantitative TP73 transcript analysis in hepatocellular carcinomas. Stiewe, T., Tuve, S., Peter, M., Tannapfel, A., Elmaagacli, A.H., Pützer, B.M. Clin. Cancer Res. (2004) [Pubmed]
  4. Different expression of P14ARF defines two groups of breast carcinomas in terms of TP73 expression and TP53 mutational status. Domínguez, G., Silva, J., Silva, J.M., García, J.M., Larrondo, F.J., Vargas, J., Sanfrutos, L., Provencio, M., España, P., Bonilla, F. Genes Chromosomes Cancer (2001) [Pubmed]
  5. TP73 allelic expression in human brain and allele frequencies in Alzheimer's disease. Li, Q., Athan, E.S., Wei, M., Yuan, E., Rice, S.L., Vonsattel, J.P., Mayeux, R.P., Tycko, B. BMC Med. Genet. (2004) [Pubmed]
  6. Monoallelically expressed gene related to p53 at 1p36, a region frequently deleted in neuroblastoma and other human cancers. Kaghad, M., Bonnet, H., Yang, A., Creancier, L., Biscan, J.C., Valent, A., Minty, A., Chalon, P., Lelias, J.M., Dumont, X., Ferrara, P., McKeon, F., Caput, D. Cell (1997) [Pubmed]
  7. The tyrosine kinase c-Abl regulates p73 in apoptotic response to cisplatin-induced DNA damage. Gong, J.G., Costanzo, A., Yang, H.Q., Melino, G., Kaelin, W.G., Levrero, M., Wang, J.Y. Nature (1999) [Pubmed]
  8. DeltaNp73, a dominant-negative inhibitor of wild-type p53 and TAp73, is up-regulated in human tumors. Zaika, A.I., Slade, N., Erster, S.H., Sansome, C., Joseph, T.W., Pearl, M., Chalas, E., Moll, U.M. J. Exp. Med. (2002) [Pubmed]
  9. Mitogen activation induces the enhanced synthesis of two heat-shock proteins in human lymphocytes. Haire, R.N., Peterson, M.S., O'Leary, J.J. J. Cell Biol. (1988) [Pubmed]
  10. P73 functionally replaces p53 in Adriamycin-treated, p53-deficient breast cancer cells. Vayssade, M., Haddada, H., Faridoni-Laurens, L., Tourpin, S., Valent, A., Bénard, J., Ahomadegbe, J.C. Int. J. Cancer (2005) [Pubmed]
  11. Effects of pharmacokinetic modulating chemotherapy using oral UFT and continuous venous 5FU infusion on the prognosis of irradiated rectal carcinomas with p53 overexpression. Kusunoki, M., Yanagi, H., Kotera, H., Noda, M., Yamamura, T. Int. J. Oncol. (1998) [Pubmed]
  12. p53 interference and growth inhibition in p53-mutant and overexpressing endometrial cancer cell lines. Janicek, M.F., Angioli, R., Unal, A.D., Sevin, B.U., Madrigal, M., Estape, R., Averette, H.E. Gynecol. Oncol. (1997) [Pubmed]
  13. Honokiol induces apoptosis through p53-independent pathway in human colorectal cell line RKO. Wang, T., Chen, F., Chen, Z., Wu, Y.F., Xu, X.L., Zheng, S., Hu, X. World J. Gastroenterol. (2004) [Pubmed]
  14. Transdominant DeltaTAp73 isoforms are frequently up-regulated in ovarian cancer. Evidence for their role as epigenetic p53 inhibitors in vivo. Concin, N., Becker, K., Slade, N., Erster, S., Mueller-Holzner, E., Ulmer, H., Daxenbichler, G., Zeimet, A., Zeillinger, R., Marth, C., Moll, U.M. Cancer Res. (2004) [Pubmed]
  15. Oncogenes induce and activate endogenous p73 protein. Zaika, A., Irwin, M., Sansome, C., Moll, U.M. J. Biol. Chem. (2001) [Pubmed]
  16. Transcriptional inactivation of TP73 expression in oligodendroglial tumors. Dong, S., Pang, J.C., Hu, J., Zhou, L.F., Ng, H.K. Int. J. Cancer (2002) [Pubmed]
  17. Expression of p53-related protein p63 in the gastrointestinal tract and in esophageal metaplastic and neoplastic disorders. Glickman, J.N., Yang, A., Shahsafaei, A., McKeon, F., Odze, R.D. Hum. Pathol. (2001) [Pubmed]
  18. Establishment of a cell line with AML1-MTG8, TP53, and TP73 abnormalities from acute myelogenous leukemia. Inokuchi, K., Hamaguchi, H., Taniwaki, M., Yamaguchi, H., Tanosaki, S., Dan, K. Genes Chromosomes Cancer (2001) [Pubmed]
  19. Interaction of mismatch repair protein PMS2 and the p53-related transcription factor p73 in apoptosis response to cisplatin. Shimodaira, H., Yoshioka-Yamashita, A., Kolodner, R.D., Wang, J.Y. Proc. Natl. Acad. Sci. U.S.A. (2003) [Pubmed]
  20. Mutation in p53 and de-regulation of p53-related gene expression in three human cell lines immortalized with 4-nitroquinoline 1-oxide or 60Co gamma rays. Iijima, M., Mihara, K., Kondo, T., Tsuji, T., Ishioka, C., Namba, M. Int. J. Cancer (1996) [Pubmed]
  21. CD154 induces p73 to overcome the resistance to apoptosis of chronic lymphocytic leukemia cells lacking functional p53. Dicker, F., Kater, A.P., Prada, C.E., Fukuda, T., Castro, J.E., Sun, G., Wang, J.Y., Kipps, T.J. Blood (2006) [Pubmed]
  22. beta-Carotene exacerbates DNA oxidative damage and modifies p53-related pathways of cell proliferation and apoptosis in cultured cells exposed to tobacco smoke condensate. Palozza, P., Serini, S., Di Nicuolo, F., Boninsegna, A., Torsello, A., Maggiano, N., Ranelletti, F.O., Wolf, F.I., Calviello, G., Cittadini, A. Carcinogenesis (2004) [Pubmed]
  23. Genistein, a tyrosine kinase inhibitor, enhanced radiosensitivity in human esophageal cancer cell lines in vitro: possible involvement of inhibition of survival signal transduction pathways. Akimoto, T., Nonaka, T., Ishikawa, H., Sakurai, H., Saitoh, J.I., Takahashi, T., Mitsuhashi, N. Int. J. Radiat. Oncol. Biol. Phys. (2001) [Pubmed]
  24. MDM2 and MDMX bind and stabilize the p53-related protein p73. Ongkeko, W.M., Wang, X.Q., Siu, W.Y., Lau, A.W., Yamashita, K., Harris, A.L., Cox, L.S., Poon, R.Y. Curr. Biol. (1999) [Pubmed]
  25. Methylation status of TP73 in meningiomas. Lomas, J., Amiñoso, C., Gonzalez-Gomez, P., Eva Alonso, M., Arjona, D., Lopez-Marin, I., de Campos, J.M., Isla, A., Vaquero, J., Gutierrez, M., Sarasa, J.L., Josefa Bello, M., Rey, J.A. Cancer Genet. Cytogenet. (2004) [Pubmed]
  26. Complex p63 mRNA isoform expression patterns in squamous cell carcinoma of the head and neck. Thurfjell, N., Coates, P.J., Uusitalo, T., Mahani, D., Dabelsteen, E., Dahlqvist, A., Sjöström, B., Roos, G., Nylander, K. Int. J. Oncol. (2004) [Pubmed]
  27. Structure and mutation analysis of the gene encoding DNA fragmentation factor 40 (caspase-activated nuclease), a candidate neuroblastoma tumour suppressor gene. Judson, H., van Roy, N., Strain, L., Vandesompele, J., Van Gele, M., Speleman, F., Bonthron, D.T. Hum. Genet. (2000) [Pubmed]
  28. Aberrant promoter methylation of multiple genes in oligodendrogliomas and ependymomas. Alonso, M.E., Bello, M.J., Gonzalez-Gomez, P., Arjona, D., Lomas, J., de Campos, J.M., Isla, A., Sarasa, J.L., Rey, J.A. Cancer Genet. Cytogenet. (2003) [Pubmed]
  29. Evaluation of 1p losses in primary carcinomas, local recurrences and peripheral metastases from colorectal cancer patients. Thorstensen, L., Qvist, H., Heim, S., Liefers, G.J., Nesland, J.M., Giercksky, K.E., Lothe, R.A. Neoplasia (2000) [Pubmed]
  30. Intronic deletion affecting a negative regulatory region of TP73 is related to breast and colorectal carcinomas. Peña, C., Garcia, J.M., Dominguez, G., Silva, J., Garcia, V., Carcereny, E., Vargas, J., Provencio, M., España, P., Bonilla, F. Genes Chromosomes Cancer (2004) [Pubmed]
  31. Transcriptional signature of Ecteinascidin 743 (Yondelis, Trabectedin) in human sarcoma cells explanted from chemo-naive patients. Martínez, N., Sánchez-Beato, M., Carnero, A., Moneo, V., Tercero, J.C., Fernández, I., Navarrete, M., Jimeno, J., Piris, M.A. Mol. Cancer Ther. (2005) [Pubmed]
  32. Cloning and functional analysis of human p51, which structurally and functionally resembles p53. Osada, M., Ohba, M., Kawahara, C., Ishioka, C., Kanamaru, R., Katoh, I., Ikawa, Y., Nimura, Y., Nakagawara, A., Obinata, M., Ikawa, S. Nat. Med. (1998) [Pubmed]
  33. High level expression of deltaN-p63: a mechanism for the inactivation of p53 in undifferentiated nasopharyngeal carcinoma (NPC)? Crook, T., Nicholls, J.M., Brooks, L., O'Nions, J., Allday, M.J. Oncogene (2000) [Pubmed]
  34. The transactivating isoforms of p63 are overexpressed in high-grade follicular lymphomas independent of the occurrence of p63 gene amplification. Pruneri, G., Fabris, S., Dell'Orto, P., Biasi, M.O., Valentini, S., Del Curto, B., Laszlo, D., Cattaneo, L., Fasani, R., Rossini, L., Manzotti, M., Bertolini, F., Martinelli, G., Neri, A., Viale, G. J. Pathol. (2005) [Pubmed]
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