Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review
  • Published:

The role of p73 in hematological malignancies

Leukemia volume 20, pages 757–766 (2006)Cite this article

Abstract

The P73 gene is a homologue of the P53 tumor suppressor. Owing to its structural similarity with p53, p73 was originally considered to have tumor suppressor function. However, the discovery of N-terminal truncated isoforms with oncogenic properties showed a ‘two in one’ structure of its product, p73 protein. The full-length variants are strong inducers of apoptosis, whereas the truncated isoforms inhibit proapoptotic activity of p53 and the full-length p73. Thus, p73 is involved in the regulation of cell cycle, cell death and development. Moreover, it plays a role in carcinogenesis and controls tumor sensitivity to treatment. p73 is commonly expressed in tumor cells in hematological malignancies. Overexpression of p73 protein and aberrant expression of its particular isoforms, with very low frequency of P73 hypermethylation or mutations, were found in malignant myeloproliferations, including acute myeloblastic leukemia. In contrast, hypermethylation and subsequent inactivation of the P73 gene are the most common findings in malignant lymphoproliferative disorders, especially acute lymphoblastic leukemia (ALL) and non-Hodgkin's lymphomas. Assessment of P73 methylation may provide important prognostic information, as was confirmed in patients with ALL. This review summarizes some aspects of p73 biology with particular reference to its possible pathogenetic role and prognostic significance in hematological malignancies.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2

Similar content being viewed by others

References

  1. Kaghad M, Bonnet H, Yang A, Creancier L, Biscan JC, Valent A et al. Monoallelically expressed gene related to p53 at 1p36, a region frequently deleted in neuroblastoma and other human cancers. Cell 1997; 90: 809–819.

    Article  CAS  PubMed  Google Scholar 

  2. Yang A, Kaghad M, Wang Y, Gillett E, Fleming MD, Dotsch V et al. p63, a p53 homolog at 3q27–29, encodes multiple products with transactivating, death-inducing, and dominant-negative activities. Mol Cell 1998; 2: 305–316.

    CAS  PubMed  Google Scholar 

  3. Benard J, Douc-Rasy S, Ahomadegbe JC . TP53 family members and human cancers. Hum Mutat 2003; 21: 182–191.

    CAS  PubMed  Google Scholar 

  4. Moll UM, Slade N . p63 and p73: roles in development and tumor formation. Mol Cancer Res 2004; 2: 371–386.

    CAS  PubMed  Google Scholar 

  5. Boyapati A, Kanbe E, Zhang DE . p53 alterations in myeloid leukemia. Acta Haematol 2004; 111: 100–106.

    CAS  PubMed  Google Scholar 

  6. Peller S, Rotter V . TP53 in hematological cancer: low incidence of mutations with significant clinical relevance. Hum Mutat 2003; 21: 277–284.

    CAS  PubMed  Google Scholar 

  7. Courtois S, de Fromentel CC, Hainaut P . p53 protein variants: structural and functional similarities with p63 and p73 isoforms. Oncogene 2004; 23: 631–638.

    CAS  PubMed  Google Scholar 

  8. Harms KL, Chen X . The C terminus of p53 family proteins is a cell fate determinant. Mol Cell Biol 2005; 25: 2014–2030.

    CAS  PubMed  PubMed Central  Google Scholar 

  9. Bourdon JC, Fernandes K, Murray-Zmijewski F, Liu G, Diot A, Xirodimas DP et al. p53 isoforms can regulate p53 transcriptional activity. Genes Dev 2005; 19: 2122–2137.

    CAS  PubMed  PubMed Central  Google Scholar 

  10. Rohaly G, Chemnitz J, Dehde S, Nunez AM, Heukeshoven J, Deppert W et al. A novel human p53 isoform is an essential element of the ATR-intra-S phase checkpoint. Cell 2005; 122: 21–32.

    CAS  PubMed  Google Scholar 

  11. Proves C, Manfredi JJ . The continuing saga of p53-more sleepless nights ahead. Moll Cell 2005; 19: 719–721.

    Google Scholar 

  12. Di Como CJ, Urist MJ, Babayan I, Drobnjak M, Hedvat CV, Teruya-Feldstein J et al. 63 expression profiles in human normal and tumor tissues. Clin Cancer Res 2002; 8: 494–501.

    CAS  PubMed  Google Scholar 

  13. Nylander K, Vojtesek B, Nenutil R, Lindgren B, Roos G, Zhanxiang W et al. Differential expression of p63 isoforms in normal tissues and neoplastic cells. J Pathol 2002; 198: 417–427.

    CAS  PubMed  Google Scholar 

  14. Bernassola F, Oberst A, Melino G, Pandolfi PP . The promyelocytic leukaemia protein tumour suppressor functions as a transcriptional regulator of p63. Oncogene 2005; 24: 6982–6986.

    CAS  PubMed  Google Scholar 

  15. Pruneri G, Fabris S, Dell'Orto P, Biasi MO, Valentini S, Del Curto B et al. The transactivating isoforms of p63 are overexpressed in high-grade follicular lymphomas independent of the occurrence of p63 gene amplification. J Pathol 2005; 206: 337–345.

    CAS  PubMed  Google Scholar 

  16. Hedvat CV, Teruya-Feldstein J, Puig P, Capodieci P, Dudas M, Pica N et al. Expression of p63 in diffuse large B-cell lymphoma. Appl Immunohistochem Mol Morphol 2005; 13: 237–242.

    CAS  PubMed  Google Scholar 

  17. Stiewe T, Pûtzer BM . p73 in apoptosis. Apoptosis 2001; 6: 447–452.

    CAS  PubMed  Google Scholar 

  18. Melino G, Lu X, Gasco M, Crook T, Knight RA . Functional regulation of p73 and p63: development and cancer. Trends Biochem Sci 2003; 28: 663–670.

    CAS  PubMed  Google Scholar 

  19. Yang A, Walker N, Bronson R, Kaghad M, Oosterwegel M, Bonnin J et al. p73-deficient mice have neurological, pheromonal and inflammatory defects but lack spontaneous tumours. Nature 2000; 404: 99–103.

    CAS  PubMed  Google Scholar 

  20. Herath NI, Kew MC, Whitehall VL, Walsh MD, Jass JR, Khanna KK et al. p73 is up-regulated in a subset of hepatocellular carcinomas. Hepatology 2000; 31: 601–605.

    CAS  PubMed  Google Scholar 

  21. Alonso ME, Bello MJ, Gonzalez-Gomez P, Lomas J, Arjona D, de Campos JM et al. Mutation analysis of the p73 gene in nonastrocytic brain tumours. Br J Cancer 2001; 85: 204–208.

    CAS  PubMed  PubMed Central  Google Scholar 

  22. Tominaga O, Unsal K, Zalcman G, Soussi T . Detection of p73 antibodies in patients with various types of cancer: immunological characterization. Br J Cancer 2001; 84: 57–63.

    CAS  PubMed  PubMed Central  Google Scholar 

  23. Sun XF . p73 overexpression in a prognostic factor in patients with colorectal adenocarcinoma. Clin Cancer Res 2002; 8: 165–170.

    CAS  PubMed  Google Scholar 

  24. Tannapfel A, Wasner M, Krause K, Geissler F, Katalinic A, Hauss J et al. Expression of p73 and its relation to histopathology and prognosis in hepatocellular carcinoma. J Natl Cancer Inst 1999; 91: 1154–1158.

    CAS  PubMed  Google Scholar 

  25. Dominguez G, Silva JM, Silva J, Garcia JM, Sanchez A, Navarro A et al. Wild type overexpression and high-grade malignancy in breast cancer. Breast Cancer Res 2001; 66: 183–190.

    CAS  Google Scholar 

  26. Ng SW, Yiu GK, Liu Y, Huang LW, Palnati M, Jun SH et al. Analysis of p73 in human borderline and invasive ovarian tumor. Oncogene 2000; 19: 1885–1890.

    CAS  PubMed  Google Scholar 

  27. Uramoto H, Sugio K, Oyama T, Nakata S, Ono K, Morita M et al. Expression of deltaNp73 predicts poor prognosis in lung cancer. Clin Cancer Res 2004; 10: 6905–6911.

    CAS  PubMed  Google Scholar 

  28. Melino G, De Laurenzi V, Vousden KH . p73: friend or foe in tumorigenesis. Nat Rev Cancer 2002; 2: 605–615.

    CAS  PubMed  Google Scholar 

  29. Ueda Y, Hijikata M, Takagi S, Chiba T, Shimotohno K . New p73 variants with altered C-terminal structures have varied transcriptional activities. Oncogene 1999; 18: 4993–4998.

    CAS  PubMed  Google Scholar 

  30. Levrero M, De Laurenzi V, Costanzo A, Gong J, Wang JY, Melino G . The p53/p63/p73 family of transcription factors: overlapping and distinct functions. J Cell Sci 2000; 113: 1661–1670.

    CAS  PubMed  Google Scholar 

  31. Stiewe T, Putzer BM . Role of p73 in malignancy: tumor suppressor or oncogene? Cell Death Differ 2002; 9: 237–245.

    CAS  PubMed  Google Scholar 

  32. Scaruffi P, Casciano I, Masiero L, Basso G, Romani M, Tonini GP . Lack of p73 expression in mature B-ALL and identification of three new splicing variants restricted to pre B and C-ALL indicate a role of p73 in B cell ALL differentiation. Leukemia 2000; 14: 518–519.

    CAS  PubMed  Google Scholar 

  33. Stiewe T, Zimmermann S, Frilling A, Esche H, Putzer BM . Transactivation-deficient DeltaTA-p73 acts as an oncogene. Cancer Res 2002; 62: 3598–3602.

    CAS  PubMed  Google Scholar 

  34. Stiewe T, Tuve S, Peter M, Tannapfel A, Elmaagacli AH, Putzer BM . Quantitative TP73 transcript analysis in hepatocellular carcinomas. Clin Cancer Res 2004; 10: 626–633.

    CAS  PubMed  Google Scholar 

  35. Ishimoto O, Kawahara C, Enjo K, Obinata M, Nukiwa T, Ikawa S . Possible oncogenic potential of deltaNp73: a newly identified isoform of human p73. Cancer Res 2002; 62: 636–641.

    CAS  PubMed  Google Scholar 

  36. De Laurenzi V, Costanzo A, Barcaroli D, Terrinoni A, Falco M, Annicchiarico-Petruzzelli M et al. Two new p73 splice variants, gamma and delta, with different transcriptional activity. J Exp Med 1998; 188: 1763–1768.

    CAS  PubMed  PubMed Central  Google Scholar 

  37. De Laurenzi VD, Catani MV, Terrinoni A, Corazzari M, Melino G, Costanzo A et al. Additional complexity in p73: induction by mitogens in lymphoid cells and identification of two new splicing variants epsilon and zeta. Cell Death Differ 1999; 6: 389–390.

    CAS  PubMed  Google Scholar 

  38. Dulloo I, Sabapathy K . Transactivation-dependent and independent regulation of p73 stability. J Biol Chem 2005; 280: 28203–28214.

    CAS  PubMed  Google Scholar 

  39. Zaika A, Irwin M, Sansome C, Moll UM . Oncogenes induce and activate endogenous p73 protein. J Biol Chem 2001; 276: 11310–11316.

    CAS  PubMed  Google Scholar 

  40. Irwin M, Marin MC, Phillips AC, Seelan RS, Smith DI, Liu W et al. Role for the p53 homologue p73 in E2F-1-induced apoptosis. Nature 2000; 407: 645–648.

    CAS  PubMed  Google Scholar 

  41. Lissy NA, Davis PK, Irwin M, Kaelin WG, Dowdy SF . A common E2F-1 and p73 pathway mediates cell death induced by TCR activation. Nature 2000; 407: 642–645.

    CAS  PubMed  Google Scholar 

  42. Ramadan S, Terrinoni A, Catani MV, Sayan AE, Knight RA, Mueller M et al. p73 induces apoptosis by different mechanisms. Biochem Biophys Res Commun 2005; 33: 713–717.

    Google Scholar 

  43. Melino G, Bernassola F, Ranalli M, Yee K, Zong WX, Corazzari M et al. p73 induces apoptosis via PUMA transactivation and Bax mitochondrial translocation. J Biol Chem 2004; 279: 8076–8083.

    CAS  PubMed  Google Scholar 

  44. Flinterman M, Guelen L, Ezzati-Nik S, Killick R, Melino G, Tominaga K et al. E1A activates transcription of p73 and Noxa to induce apoptosis. J Biol Chem 2005; 280: 5945–5959.

    CAS  PubMed  Google Scholar 

  45. Stiewe T, Theseling CC, Putzer BM . Transactivation-deficient Delta TA-p73 inhibits p53 by direct competition for DNA binding: implications for tumorigenesis. J Biol Chem 2002; 277: 14177–14185.

    CAS  PubMed  Google Scholar 

  46. Chen X . The p53 family: same response, different signals? Mol Med Today 1999; 5: 387–392.

    CAS  PubMed  Google Scholar 

  47. Jost CA, Marin MC, Kaelin Jr WG . p73 is a simian [correction of human] p53-related protein that can induce apoptosis. Nature 1997; 389: 191–194.

    CAS  PubMed  Google Scholar 

  48. Di Como CJ, Gaiddon C, Prives C . p73 function is inhibited by tumor-derived p53 mutants in mammalian cells. Mol Cell Biol 1999; 19: 1438–1449.

    CAS  PubMed  PubMed Central  Google Scholar 

  49. Donehower LA, Harvey M, Slagle BL, McArthur MJ, Montgomery Jr CA, Butel JS et al. Mice deficient for p53 are developmentally normal but susceptible to spontaneous tumours. Nature 1992; 356: 215–221.

    CAS  PubMed  Google Scholar 

  50. Moll UM, Erster S, Zaika A . p53, p63 and p73 – solos, alliances and feuds among family members. Biochim Biophys Acta 2001; 1552: 47–59.

    CAS  PubMed  Google Scholar 

  51. Stiewe T, Putzer BM . Role of p73 in malignancy: tumor suppressor or oncogene? Cell Death Differ 2002; 9: 237–245.

    CAS  PubMed  Google Scholar 

  52. Sahu GR, Das BR . Alteration of p73 in pediatric de novo acute lymphoblastic leukemia. Biochem Biophys Res Commun 2005; 327: 750–755.

    CAS  PubMed  Google Scholar 

  53. Gutierrez MI, Siraj AK, Bhargava M, Ozbek U, Banavali S, Chaudhary MA et al. Concurrent methylation of multiple genes in childhood ALL: correlation with phenotype and molecular subgroup. Leukemia 2003; 17: 1845–1850.

    CAS  PubMed  Google Scholar 

  54. Corn PG, Kuerbitz SJ, van Noesel MM, Esteller M, Compitello N, Baylin SB et al. Transcriptional silencing of the p73 gene in acute lymphoblastic leukemia and Burkitt's lymphoma is associated with 5′ CpG island methylation. Cancer Res 1999; 59: 3352–3356.

    CAS  PubMed  Google Scholar 

  55. Garcia-Manero G, Daniel J, Smith TL, Kornblau SM, Lee MS, Kantarjian HM et al. DNA methylation of multiple promoter-associated CpG islands in adult acute lymphocytic leukemia. Clin Cancer Res 2002; 8: 2217–2224.

    CAS  PubMed  Google Scholar 

  56. Roman-Gomez J, Jimenez-Velasco A, Castillejo JA, Agirre X, Barrios M, Navarro G et al. Promoter hypermethylation of cancer-related genes: a strong independent prognostic factor in acute lymphoblastic leukemia. Blood 2004; 104: 2492–2498.

    CAS  PubMed  Google Scholar 

  57. Gutierrez MI, Siraj AK, Ibrahim MM, Hussain A, Bhatia K . Childhood and adult ALL: differences in epigenetic lesions associated with cell cycle genes. Am J Hematol 2005; 80: 158–160.

    PubMed  Google Scholar 

  58. Roman-Gomez J, Jimenez-Velasco A, Agirre X, Prosper F, Heiniger A, Torres A . Lack of CpG island methylator phenotype defines a clinical subtype of T-cell acute lymphoblastic leukemia associated with good prognosis. J Clin Oncol 2005; 23: 7043–7049.

    CAS  PubMed  Google Scholar 

  59. Kawano S, Miller CW, Gombart AF, Bartram CR, Matsuo Y, Asou H et al. Loss of p73 gene expression in leukemias/lymphomas due to hypermethylation. Blood 1999; 94: 1113–1120.

    CAS  PubMed  Google Scholar 

  60. Leupin N, Luthi A, Novak U, Grob TJ, Hugli B, Graber H et al. P73 status in B-cell chronic lymphocytic leukemia. Leuk Lymphoma 2004; 45: 1205–1207.

    CAS  PubMed  Google Scholar 

  61. Novak U, Grob TJ, Baskaynak G, Peters UR, Aebi S, Zwahlen D et al. Overexpression of the p73 gene is a novel finding in high-risk B-cell chronic lymphocytic leukemia. Ann Oncol 2001; 12: 981–986.

    CAS  PubMed  Google Scholar 

  62. Sahu GR, Mishra R, Nagpal JK, Das BR . Alteration of p73 in acute myelogenous leukemia. Am J Hematol 2005; 79: 1–7.

    CAS  PubMed  Google Scholar 

  63. Stirewalt DL, Clurman B, Appelbaum FR, Willman CL, Radich JP . p73 mutations and expression in adult de novo acute myelogenous leukemia. Leukemia 1999; 13: 985–990.

    CAS  PubMed  Google Scholar 

  64. Ekmekci CG, Gutierrez MI, Siraj AK, Ozbek U, Bhatia K . Aberrant methylation of multiple tumor suppressor genes in acute myeloid leukemia. Am J Hematol 2004; 77: 233–240.

    CAS  PubMed  Google Scholar 

  65. Chim CS, Kwong YL, Fung TK, Liang R . Methylation profiling in multiple myeloma. Leuk Res 2004; 28: 379–385.

    CAS  PubMed  Google Scholar 

  66. Galm O, Wilop S, Luders C, Jost E, Gehbauer G, Herman JG et al. Clinical implications of aberrant DNA methylation patterns in acute myelogenous leukemia. Ann Hematol 2005; 18: 1–8.

    Google Scholar 

  67. Peters UR, Tschan MP, Kreuzer KA, Baskaynak G, Lass U, Tobler A et al. Distinct expression patterns of the p53-homologue p73 in malignant and normal hematopoiesis assessed by a novel real-time reverse transcription-polymerase chain reaction assay and protein analysis. Cancer Res 1999; 59: 4233–4236.

    CAS  PubMed  Google Scholar 

  68. Tschan MP, Grob TJ, Peters UR, Laurenzi VD, Huegli B, Kreuzer KA et al. Enhanced p73 expression during differentiation and complex p73 isoforms in myeloid leukemia. Biochem Biophys Res Commun 2000; 277: 62–65.

    CAS  PubMed  Google Scholar 

  69. Rizzo MG, Giombini E, Diverio D, Vignetti M, Sacchi A, Testa U et al. Analysis of p73 expression pattern in acute myeloid leukemias: lack of DeltaN-p73 expression is a frequent feature of acute promyelocytic leukemia. Leukemia 2004; 18: 1804–1809.

    CAS  PubMed  Google Scholar 

  70. Stoffel A, Filippa D, Rao PH . The p73 locus is commonly deleted in non-Hodgkin's lymphomas. Leuk Res 2004; 28: 1341–1345.

    CAS  PubMed  Google Scholar 

  71. Siu LL, Chan JK, Wong KF, Kwong YL . Specific patterns of gene methylation in natural killer cell lymphomas : p73 is consistently involved. Am J Pathol 2002; 160: 59–66.

    CAS  PubMed  Google Scholar 

  72. Gonzalez-Gomez P, Bello MJ, Arjona D, Alonso ME, Lomas J, Aminoso C et al. CpG island methylation of tumor-related genes in three primary central nervous system lymphomas in immunocompetent patients. Cancer Genet Cytogenet 2003; 142: 21–24.

    CAS  PubMed  Google Scholar 

  73. Galm O, Wilop S, Reichelt J, Jost E, Gehbauer G, Herman JG et al. DNA methylation changes in multiple myeloma. Leukemia 2004; 18: 1687–1692.

    CAS  PubMed  Google Scholar 

  74. Seidl S, Ackermann J, Kaufmann H, Keck A, Nosslinger T, Zielinski CC et al. DNA-methylation analysis identifies the E-cadherin gene as a potential marker of disease progression in patients with monoclonal gammopathies. Cancer 2004; 100: 2598–2606.

    CAS  PubMed  Google Scholar 

  75. Chim CS, Wong SY, Kwong YL . Aberrant gene promoter methylation in acute promyelocytic leukemia: profile and prognostic significance. Br J Haematol 2003; 122: 571–578.

    CAS  PubMed  Google Scholar 

  76. Schmelz K, Wagner M, Dorken B, Tamm I . 5-Aza-2′-deoxycytidine induces p21WAF expression by demethylation of p73 leading to p53-independent apoptosis in myeloid leukemia. Int J Cancer 2005; 114: 683–695.

    CAS  PubMed  Google Scholar 

  77. Irvin MS . Family feud in chemosensitivity. P73 and mutant p53. Cell Cycle 2004; 3: 319–323.

    Google Scholar 

  78. Liu M, Taketani T, Li R, Takita J, Taki T, Yang HW et al. Loss of p73 gene expression in lymphoid leukemia cell lines is associated with hypermethylation. Leuk Res 2001; 25: 441–447.

    CAS  PubMed  Google Scholar 

  79. Garcia-Manero G, Bueso-Ramos C, Daniel J, Williamson J, Kantarjian HM, Issa JP . DNA methylation patterns at relapse in adult acute lymphocytic leukemia. Clin Cancer Res 2002; 8: 1897–1903.

    CAS  PubMed  Google Scholar 

  80. Bueso-Ramos C, Xu Y, McDonnell TJ, Brisbay S, Pierce S, Kantarjian H et al. Protein expression of a triad of frequently methylated genes, p73, p57Kip2, and p15, has prognostic value in adult acute lymphocytic leukemia independently of its methylation status. J Clin Oncol 2005; 23: 3932–3939.

    CAS  PubMed  Google Scholar 

  81. Herranz M, Urioste M, Santos J, Martinez-Delgado JB, Rivas C, Benitez J et al. Allelic losses and genetic instabilities of PTEN and p73 in non-Hodgkin lymphomas. Leukemia 2000; 14: 1325–1327.

    CAS  PubMed  Google Scholar 

  82. Rossi D, Capello D, Gloghini A, Franceschetti S, Paulli M, Bhatia K et al. Aberrant promoter methylation of multiple genes throughout the clinico-pathologic spectrum of B-cell neoplasia. Haematologica 2004; 89: 154–164.

    CAS  PubMed  Google Scholar 

  83. Martinez-Delgado B, Melendez B, Cuadros M, Jose Garcia M, Nomdedeu J, Rivas C et al. Frequent inactivation of the p73 gene by abnormal methylation or LOH in non-Hodgkin's lymphomas. Int J Cancer 2002; 102: 15–19.

    CAS  PubMed  Google Scholar 

  84. Kawamata N, Inagaki N, Mizumura S, Sugimoto KJ, Sakajiri S, Ohyanagi-Hara M et al. Methylation status analysis of cell cycle regulatory genes (p16INK4A, p15INK4B, p21Waf1/Cip1, p27Kip1 and p73) in natural killer cell disorders. Eur J Haematol 2005; 74: 424–429.

    CAS  PubMed  Google Scholar 

  85. van Doorn R, Zoutman WH, Dijkman R, de Menezes RX, Commandeur S, Mulder AA et al. Epigenetic profiling of cutaneous T-cell lymphoma: promoter hypermethylation of multiple tumor suppressor genes including BCL7a, PTPRG, and p73. J Clin Oncol 2005; 23: 3886–3896.

    CAS  PubMed  Google Scholar 

  86. Hishida A, Matsuo K, Tajima K, Ogura M, Kagami Y, Taji H et al. Polymorphisms of p53 Arg72Pro, p73 G4C14-to-A4T14 at exon 2 and p21 Ser31Arg and the risk of non-Hodgkin's lymphoma in Japanese. Leuk Lymphoma 2004; 45: 957–964.

    CAS  PubMed  Google Scholar 

  87. Schultheis B, Kramer A, Willer A, Hegenbart U, Goldschmidt H, Hehlmann R . Analysis of p73 and p53 gene deletions in multiple myeloma. Leukemia 1999; 13: 2099–2103.

    CAS  PubMed  Google Scholar 

  88. Farinha NJ, Shaker S, Lemaire M, Momparler L, Bernstein M, Momparler RL . Activation of expression of p15, p73 and E-cadherin in leukemic cells by different concentrations of 5-aza-2′-deoxycytidine (Decitabine). Anticancer Res 2004; 24: 75–78.

    CAS  PubMed  Google Scholar 

  89. Das S, El-Deiry WS, Somasundaram K . Efficient growth inhibition of HPV 16 E6-expressing cells by an adenovirus-expressing p53 homologue p73beta. Oncogene 2003; 22: 8394–8402.

    CAS  PubMed  Google Scholar 

  90. Das S, El-Deiry WS, Somasundaram K . Regulation of the p53 homolog p73 by adenoviral oncogene E1A. J Biol Chem 2003; 278: 18313–18320.

    CAS  PubMed  Google Scholar 

  91. Das S, Nama S, Antony S, Somasundaram K . p73 beta-expressing recombinant adenovirus: a potential anticancer agent. Cancer Gene Ther 2005; 12: 417–426.

    CAS  PubMed  Google Scholar 

  92. Rodicker F, Putzer BM . p73 is effective in p53-null pancreatic cancer cells resistant to wild-type TP53 gene replacement. Cancer Res 2003; 63: 2737–2741.

    PubMed  Google Scholar 

  93. Brummelkamp TR, Bernards R, Agami R . Stable suppression of tumorigenicity by virus-mediated RNA interference. Cancer Cell 2002; 2: 243–247.

    CAS  PubMed  Google Scholar 

  94. Simoes-Wust AP, Sigrist B, Belyanskaya L, Hopkins Donaldson S, Stahel RA, Zangemeister-Wittke U . DeltaNp73 antisense activates PUMA and induces apoptosis in neuroblastoma cells. J Neurooncol 2005; 72: 29–34.

    CAS  PubMed  Google Scholar 

  95. Bensaad K, Le Bras M, Unsal K, Strano S, Blandino G, Tominaga O et al. Change of conformation of the DNA-binding domain of p53 is the only key element for binding of and interference with p73. J Biol Chem 2003; 278: 10546–10555.

    CAS  PubMed  Google Scholar 

  96. Bykov VJ, Issaeva N, Shilov A, Hultcrantz M, Pugacheva E, Chumakov P et al. Restoration of the tumor suppressor function to mutant p53 by a low-molecular-weight compound. Nat Med 2002; 8: 282–288.

    CAS  PubMed  Google Scholar 

  97. Martinez LA, Naguibneva I, Lehrmann H, Vervisch A, Tchenio T, Lozano G et al. Synthetic small inhibiting RNAs: efficient tools to inactivate oncogenic mutations and restore p53 pathways. Proc Natl Acad Sci USA 2002; 99: 14849–14854.

    CAS  PubMed  PubMed Central  Google Scholar 

  98. Peng Y, Li C, Chen L, Sebti S, Chen J . Rescue of mutant p53 transcription function by ellipticine. Oncogene 2003; 22: 4478–4487.

    CAS  PubMed  Google Scholar 

  99. Lunghi P, Costanzo A, Levrero M, Bonati A . Treatment with arsenic trioxide (ATO) and MEK1 inhibitor activates the p73–p53AIP1 apoptotic pathway in leukemia cells. Blood 2004; 104: 519–525.

    CAS  PubMed  Google Scholar 

Download references

Acknowledgements

The authors' own work was supported by the Mol. Med Centre of Excellence and the grants from The State Committee for Scientific Research, Warsaw, Poland (nos. 507-11-272, 507-11-248 and 515-02-003) (AP, TR and PS), The Medical University of Lodz (no. 503-106-2) (AP, TR and PS), The Swedish (BJ and BZ) and Stockholm (BZ) Cancer Societies, The Swedish Institute (AP and BZ), The Swedish Science Foundation (BJ and BZ), the Karolinska Institutet Foundation (KI Cancer), the Åke Wiberg Foundation, the Swedish Medical Society (BJ) and The European Commission (BZ).

Author information

Authors and Affiliations

  1. Department of Hematology, Medical University of Lodz and Copernicus Memorial Hospital, Lodz, Poland

    A Pluta, T Robak & P Smolewski

  2. Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden

    U Nyman, B Joseph & B Zhivotovsky

Authors
  1. A Pluta
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. U Nyman
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. B Joseph
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. T Robak
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. B Zhivotovsky
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. P Smolewski
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to P Smolewski.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Pluta, A., Nyman, U., Joseph, B. et al. The role of p73 in hematological malignancies. Leukemia 20, 757–766 (2006). https://doi.org/10.1038/sj.leu.2404166

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.leu.2404166

Keywords

This article is cited by

Search

Advanced search

Quick links