Uncovering the role of p53 splice variants in human malignancy: A clinical perspective

OncoTargets and Therapy

Volumn 7, Issue , 2013, Pages 57-67

  Surget, Sylvanie ^a   Khoury, Marie P ^a   Bourdon, Jean Christophe ^a  

^a UNIVERSITY OF DUNDEE   (United Kingdom)

Author keywords

Alternative splicing; Cancer; Isoforms; p53; p63; p73

Indexed keywords

PROTEIN P47; PROTEIN P53; PROTEIN P53ALPHA; PROTEIN P53BETA; PROTEIN P53GAMMA; UNCLASSIFIED DRUG;

APOPTOSIS; BIOLOGICAL ACTIVITY; CANCER INHIBITION; CARCINOGENESIS; CELL CYCLE ARREST; GENE MUTATION; GENETIC VARIABILITY; HUMAN; MALIGNANT NEOPLASTIC DISEASE; MOLECULARLY TARGETED THERAPY; NONHUMAN; ONCOGENE; PROTEIN BINDING; PROTEIN EXPRESSION; PROTEIN FUNCTION; PROTEIN MODIFICATION; PROTEIN PROTEIN INTERACTION; REVIEW; TP53 GENE; TRANSCRIPTION INITIATION;

EID: 84890942102     PISSN: 11786930     EISSN: None     Source Type: Journal    
DOI: 10.2147/OTT.S53876     Document Type: Review

References (108)

1. Bénard J, Douc-Rasy S, Ahomadegbe JC. TP53 family members and human cancers. Hum Mutat. 2003;21(3):182-191.
2. Melino G, Lu X, Gasco M, Crook T, Knight RA. Functional regulation of p73 and p63: development and cancer. Trends Biochem Sci. 2003;28(12):663-670.
3. Flores ER, Sengupta S, Miller JB, et al. Tumor predisposition in mice mutant for p63 and p73: evidence for broader tumor suppressor functions for the p53 family. Cancer Cell. 2005;7(4):363-373.
4. Khoury MP, Bourdon JC. p53 Isoforms: an intracellular microprocessor? Genes Cancer. 2011;2(4):453-465.
5. Kaghad M, Bonnet H, Yang A, et al. Monoallelically expressed gene related to p53 at 1p36, a region frequently deleted in neuroblastoma and other human cancers. Cell. 1997;90(4):809-819.
6. Yang A, Kaghad M, Wang Y, et al. p63, A p53 homolog at 3q27-29, encodes multiple products with transactivating, death-inducing, and dominant-negative activities. Mol Cell. 1998;2(3):305-316.
7. Ding Y, Inoue T, Kamiyama J, et al. Molecular cloning and functional characterization of the upstream promoter region of the human p73 gene. DNA Res. 1999;6(5):347-351.
8. Murray-Zmijewski F, Lane DP, Bourdon JC. p53/p63/p73 Isoforms: an orchestra of isoforms to harmonise cell differentiation and response to stress. Cell Death Differ. 2006;13(6):962-972.
9. Dötsch V, Bernassola F, Coutandin D, Candi E, Melino G. p63 And p73, the ancestors of p53. Cold Spring Harb Perspect Biol. 2010;2(9):a004887.
10. Oren M. Decision making by p53: life, death and cancer. Cell Death Differ. 2003;10(4):431-442.
11. Meek DW, Anderson CW. Posttranslational modification of p53: cooperative integrators of function. Cold Spring Harb Perspect Biol. 2009;1(6):a000950.
12. Honda R, Tanaka H, Yasuda H. Oncoprotein MDM2 is a ubiquitin ligase E3 for tumor suppressor p53. FEBS Lett. 1997;420(1):25-27.
13. Leng RP, Lin Y, Ma W, et al. Pirh2, a p53-induced ubiquitin-protein ligase, promotes p53 degradation. Cell. 2003;112(6):779-791.
14. el-Deiry WS, Kern SE, Pietenpol JA, Kinzler KW, Vogelstein B. Definition of a consensus binding site for p53. Nat Genet. 1992;1(1):45-49.
15. Funk WD, Pak DT, Karas RH, Wright WE, Shay JW. A transcriptionally active DNA-binding site for human p53 protein complexes. Mol Cell Biol. 1992;12(6):2866-2871.
16. Li M, He Y, Dubois W, Wu X, Shi J, Huang J. Distinct regulatory mechanisms and functions for p53-activated and p53-repressed DNA damage response genes in embryonic stem cells. Mol Cell. 2012;46(1): 30-42.
17. Donehower LA, Harvey M, Slagle BL, et al. Mice deficient for p53 are developmentally normal but susceptible to spontaneous tumours. Nature. 1992;356(6366):215-221.
18. Hall PA, McKee PH, Menage HD, Dover R, Lane DP. High levels of p53 protein in UV-irradiated normal human skin. Oncogene. 1993;8(1): 203-207.
19. Taylor WR, Stark GR. Regulation of the G2/M transition by p53. Oncogene. 2001;20(15):1803-1815.
20. Sperka T, Wang J, Rudolph KL. DNA damage checkpoints in stem cells, ageing and cancer. Nat Rev Mol Cell Biol. 2012;13(9):579-590.
21. Kuribayashi K, El-Deiry WS. Regulation of programmed cell death by the p53 pathway. Adv Exp Med Biol. 2008;615:201-221.
22. Wu GS, Burns TF, McDonald ER 3rd, et al. KILLER/DR5 is a DNA damage-inducible p53-regulated death receptor gene. Nat Genet. 1997;17(2):141-143.
23. Sheikh MS, Burns TF, Huang Y, et al. p53-Dependent and-independent regulation of the death receptor KILLER/DR5 gene expression in response to genotoxic stress and tumor necrosis factor alpha. Cancer Res. 1998;58(8):1593-1598.
24. Owen-Schaub LB, Zhang W, Cusack JC, et al. Wild-type human p53 and a temperature-sensitive mutant induce Fas/APO-1 expression. Mol Cell Biol. 1995;15(6):3032-3040.
25. Caelles C, Helmberg A, Karin M. p53-Dependent apoptosis in the absence of transcriptional activation of p53-target genes. Nature. 1994;370(6486):220-223.
26. Moll UM, Wolff S, Speidel D, Deppert W. Transcription-independent pro-apoptotic functions of p53. Curr Opin Cell Biol. 2005;17(6): 631-636.
27. Marchenko ND, Zaika A, Moll UM. Death signal-induced localization of p53 protein to mitochondria. A potential role in apoptotic signaling. J Biol Chem. 2000;275(21):16202-16212.
28. Mihara M, Erster S, Zaika A, et al. p53 Has a direct apoptogenic role at the mitochondria. Mol Cell. 2003;11(3):577-590.
29. Crighton D, Wilkinson S, O'Prey J, et al. DRAM, a p53-induced modulator of autophagy, is critical for apoptosis. Cell. 2006;126(1):121-134.
30. Maddocks OD, Vousden KH. Metabolic regulation by p53. J Mol Med (Berl). 2011;89(3):237-245.
31. Pant V, Quintás-Cardama A, Lozano G. The p53 pathway in hematopoiesis: lessons from mouse models, implications for humans. Blood. 2012;120(26):5118-5127.
32. Quadrato G, Di Giovanni S. Gatekeeper between quiescence and differentiation: p53 in axonal outgrowth and neurogenesis. Int Rev Neurobiol. 2012;105:71-89.
33. Levine AJ, Tomasini R, McKeon FD, Mak TW, Melino G. The p53 family: guardians of maternal reproduction. Nat Rev Mol Cell Biol. 2011;12(4):259-265.
34. Lane DP, Crawford LV. T antigen is bound to a host protein in SV40-transformed cells. Nature. 1979;278(5701):261-263.
35. Linzer DI, Levine AJ. Characterization of a 54 K dalton cellular SV40 tumor antigen present in SV40-transformed cells and uninfected embryonal carcinoma cells. Cell. 1979;17(1):43-52.
36. Reich NC, Levine AJ. Growth regulation of a cellular tumour antigen, p53, in nontransformed cells. Nature. 1984;308(5955):199-201.
37. Mercer WE, Avignolo C, Baserga R. Role of the p53 protein in cell proliferation as studied by microinjection of monoclonal antibodies. Mol Cell Biol. 1984;4(2):276-281.
38. Mowat M, Cheng A, Kimura N, Bernstein A, Benchimol S. Rearrangements of the cellular p53 gene in erythroleukaemic cells transformed by Friend virus. Nature. 1985;314(6012):633-636.
39. Munroe DG, Rovinski B, Bernstein A, Benchimol S. Loss of a highly conserved domain on p53 as a result of gene deletion during Friend virus-induced erythroleukemia. Oncogene. 1988;2(6):621-624.
40. Hinds P, Finlay C, Levine AJ. Mutation is required to activate the p53 gene for cooperation with the ras oncogene and transformation. J Virol. 1989;63(2):739-746.
41. Finlay CA, Hinds PW, Levine AJ. The p53 proto-oncogene can act as a suppressor of transformation. Cell. 1989;57(7):1083-1093.
42. Eliyahu D, Michalovitz D, Eliyahu S, Pinhasi-Kimhi O, Oren M. Wild-type p53 can inhibit oncogene-mediated focus formation. Proc Natl Acad Sci U S A. 1989;86(22):8763-8767.
43. Jenkins JR, Rudge K, Currie GA. Cellular immortalization by a cDNA clone encoding the transformation-associated phosphoprotein p53. Nature. 1984;312(5995):651-654.
44. Malkin D, Li FP, Strong LC, et al. Germ line p53 mutations in a familial syndrome of breast cancer, sarcomas, and other neoplasms. Science. 1990;250(4985):1233-1238.
45. Srivastava S, Zou ZQ, Pirollo K, Blattner W, Chang EH. Germ-line transmission of a mutated p53 gene in a cancer-prone family with Li-Fraumeni syndrome. Nature. 1990;348(6303):747-749.
46. Levine AJ, Momand J, Finlay CA. The p53 tumour suppressor gene. Nature. 1991;351(6326):453-456.
47. Hollstein M, Sidransky D, Vogelstein B, Harris CC. p53 mutations in human cancers. Science. 1991;253(5015):49-53.
48. Levine AJ. The common mechanisms of transformation by the small DNA tumor viruses: the inactivation of tumor suppressor gene products: p53. Virology. 2009;384(2):285-293.
49. Goldstein I, Marcel V, Olivier M, Oren M, Rotter V, Hainaut P. Understanding wild-type and mutant p53 activities in human cancer: new landmarks on the way to targeted therapies. Cancer Gene Ther. 2011;18(1):2-11.
50. Freed-Pastor WA, Prives C. Mutant p53: one name, many proteins. Genes Dev. 2012;26(12):1268-1286.
51. Dumont P, Leu JI, Della Pietra AC 3rd, George DL, Murphy M. The codon 72 polymorphic variants of p53 have markedly different apoptotic potential. Nat Genet. 2003;33(3):357-365.
52. Garritano S, Gemignani F, Palmero EI, et al. Detailed haplotype analysis at the TP53 locus in p. R337H mutation carriers in the population of Southern Brazil: evidence for a founder effect. Hum Mutat. 2010;31(2): 143-150.
53. Wu D, Zhang Z, Chu H, Xu M, Xue Y, Zhu H. Intron 3 sixteen base pairs duplication polymorphism of p53 contributes to breast cancer susceptibility: evidence from meta-analysis. PLoS One. 2013;8(4):e61662.
54. Matlashewski G, Lamb P, Pim D, Peacock J, Crawford L, Benchimol S. Isolation and characterization of a human p53 cDNA clone: expression of the human p53 gene. EMBO J. 1984;3(13):3257-3262.
55. Wolf D, Harris N, Goldfinger N, Rotter V. Isolation of a full-length mouse cDNA clone coding for an immunologically distinct p53 molecule. Mol Cell Biol. 1985;5(1):127-132.
56. Flaman JM, Waridel F, Estreicher A, et al. The human tumour suppressor gene p53 is alternatively spliced in normal cells. Oncogene. 1996;12(4):813-818.
57. Arai N, Nomura D, Yokota K, et al. Immunologically distinct p53 molecules generated by alternative splicing. Mol Cell Biol. 1986;6(9): 3232-3239.
58. Bourdon JC, Fernandes K, Murray-Zmijewski F, et al. p53 Isoforms can regulate p53 transcriptional activity. Genes Dev. 2005;19(18): 2122-2137.
59. Fujita K, Mondal AM, Horikawa I, et al. p53 Isoforms Delta133p53 and p53beta are endogenous regulators of replicative cellular senescence. Nat Cell Biol. 2009;11(9):1135-1142.
60. Marcel V, Petit I, Murray-Zmijewski F, et al. Diverse p63 and p73 isoforms regulate Delta133p53 expression through modulation of the internal TP53 promoter activity. Cell Death Differ. 2012;19(5):816-826.
61. Silden E, Hjelle SM, Wergeland L, et al. Expression of TP53 isoforms p53beta or p53gamma enhances chemosensitivity in TP53(null) cell lines. PLoS One. 2013;8(2):e56276.
62. Ray PS, Grover R, Das S. Two internal ribosome entry sites mediate the translation of p53 isoforms. EMBO Rep. 2006;7(4):404-410.
63. Yin Y, Stephen CW, Luciani MG, Fahraeus R. p53 Stability and activity is regulated by Mdm2-mediated induction of alternative p53 translation products. Nat Cell Biol. 2002;4(6):462-467.
64. Courtois S, Verhaegh G, North S, et al. DeltaN-p53, a natural isoform of p53 lacking the first transactivation domain, counteracts growth suppression by wild-type p53. Oncogene. 2002;21(44):6722-6728.
65. Ghosh A, Stewart D, Matlashewski G. Regulation of human p53 activity and cell localization by alternative splicing. Mol Cell Biol. 2004;24(18): 7987-7997.
66. Aoubala M, Murray-Zmijewski F, Khoury MP, et al. p53 Directly transactivates Delta133p53alpha, regulating cell fate outcome in response to DNA damage. Cell Death Differ. 2011;18(2):248-258.
67. Marcel V, Vijayakumar V, Fernández-Cuesta L, et al. p53 Regulates the transcription of its Delta133p53 isoform through specific response elements contained within the TP53 P2 internal promoter. Oncogene. 2010;29(18):2691-2700.
68. Bernard H, Garmy-Susini B, Ainaoui N, et al. The p53 isoform, Delta133p53alpha, stimulates angiogenesis and tumour progression. Oncogene. 2013;32(17):2150-2160.
69. Wei J, Noto J, Zaika E, et al. Pathogenic bacterium Helicobacter pylori alters the expression profile of p53 protein isoforms and p53 response to cellular stresses. Proc Natl Acad Sci U S A. 2012;109(38): E2543-E2550.
70. Slatter TL, Hung N, Campbell H, et al. Hyperproliferation, cancer, and inflammation in mice expressing a Delta133p53-like isoform. Blood. 2011;117(19):5166-5177.
71. Neubauer A, He M, Schmidt CA, Huhn D, Liu ET. Genetic alterations in the p53 gene in the blast crisis of chronic myelogenous leukemia: analysis by polymerase chain reaction based techniques. Leukemia. 1993;7(4):593-600.
72. Marcel V, Perrier S, Aoubala M, et al. Delta160p53 is a novel N-terminal p53 isoform encoded by Delta133p53 transcript. FEBS Lett. 2010;584(21):4463-4468.
73. Rohaly G, Chemnitz J, Dehde S, et al. A novel human p53 isoform is an essential element of the ATR-intra-S phase checkpoint. Cell. 2005;122(1):21-32.
74. Khoury MP, Bourdon JC. The isoforms of the p53 protein. Cold Spring Harb Perspect Biol. 2010;2(3):a000927.
75. Bourdon JC, Khoury MP, Diot A, et al. p53 Mutant breast cancer patients expressing p53 gamma have as good a prognosis as wild-type p53 breast cancer patients. Breast Cancer Res. 2011;13(1):R7.
76. Avery-Kiejda KA, Zhang XD, Adams LJ, et al. Small molecular weight variants of p53 are expressed in human melanoma cells and are induced by the DNA-damaging agent cisplatin. Clin Cancer Res. 2008;14(6):1659-1668.
77. Song W, Huo SW, Lu JJ, et al. Expression of p53 isoforms in renal cell carcinoma. Chin Med J (Engl). 2009;122(8):921-926.
78. Hofstetter G, Berger A, Fiegl H, et al. Alternative splicing of p53 and p73: the novel p53 splice variant p53delta is an independent prognostic marker in ovarian cancer. Oncogene. 2010;29(13):1997-2004.
79. Marabese M, Marchini S, Marrazzo E, et al. Expression levels of p53 and p73 isoforms in stage I and stage III ovarian cancer. Eur J Cancer. 2008;44(1):131-141.
80. Boldrup L, Bourdon JC, Coates PJ, Sjöström B, Nylander K. Expression of p53 isoforms in squamous cell carcinoma of the head and neck. Eur J Cancer. 2007;43(3):617-623.
81. Anensen N, Oyan AM, Bourdon JC, Kalland KH, Bruserud O, Gjertsen BT. A distinct p53 protein isoform signature reflects the onset of induction chemotherapy for acute myeloid leukemia. Clin Cancer Res. 2006;12(13):3985-3992.
82. Takahashi R, Giannini C, Sarkaria JN, et al. p53 Isoform profiling in glioblastoma and injured brain. Oncogene. 2013;32(26):3165-3174.
83. Nutthasirikul N, Limpaiboon T, Leelayuwat C, Patrakitkomjorn S, Jearanaikoon P. Ratio disruption of the 133p53 and TAp53 isoform equilibrium correlates with poor clinical outcome in intrahepatic cholangiocarcinoma. Int J Oncol. 2013;42(4):1181-1188.
84. Terrier O, Bourdon JC, Rosa-Calatrava M. p53 Protein isoforms: key regulators in the front line of pathogen infections? PLoS Pathog. 2013;9(4):e1003246.
85. Collot-Teixeira S, Bass J, Denis F, Ranger-Rogez S. Human tumor suppressor p53 and DNA viruses. Rev Med Virol. 2004;14(5): 301-319.
86. Soria C, Estermann FE, Espantman KC, O'Shea CC. Heterochromatin silencing of p53 target genes by a small viral protein. Nature. 2010;466(7310):1076-1081.
87. Grover R, Sharathchandra A, Ponnuswamy A, Khan D, Das S. Effect of mutations on the p53 IRES RNA structure: implications for de-regulation of the synthesis of p53 isoforms. RNA Biol. 2011;8(1): 132-142.
88. Khan D, Sharathchandra A, Ponnuswamy A, Grover R, Das S. Effect of a natural mutation in the 5′ untranslated region on the translational control of p53 mRNA. Oncogene. 2013;32(35):4148-4159.
89. Franck D, Tracy L, Armata HL, et al. Glucose tolerance in mice is linked to the dose of the p53 transactivation domain. Endocr Res. Epub October 26, 2012.
90. Hinault C, Kawamori D, Liew CW, et al. Delta40 isoform of p53 controls beta-cell proliferation and glucose homeostasis in mice. Diabetes. 2011;60(4):1210-1222.
91. Ungewitter E, Scrable H. Delta40p53 controls the switch from pluripotency to differentiation by regulating IGF signaling in ESCs. Genes Dev. 2010;24(21):2408-2419.
92. Pehar M, O'Riordan KJ, Burns-Cusato M, et al. Altered longevity-assurance activity of p53:p44 in the mouse causes memory loss, neurodegeneration and premature death. Aging Cell. 2010;9(2): 174-190.
93. Maier B, Gluba W, Bernier B, et al. Modulation of mammalian life span by the short isoform of p53. Genes Dev. 2004;18(3):306-319.
94. Terrier O, Diederichs A, Dubois J, et al. Influenza NS1 interacts with p53 and alters its binding to p53-responsive genes, in a promoter-dependent manner. FEBS Lett. 2013;587(18):2965-2971.
95. Terrier O, Marcel V, Cartet G, et al. Influenza A viruses control expression of proviral human p53 isoforms p53beta and Delta133p53alpha. J Virol. 2012;86(16):8452-8460.
96. Terrier O, Textoris J, Carron C, Marcel V, Bourdon JC, Rosa-Calatrava M. Host microRNA molecular signatures associated with human H1N1 and H3N2 influenza A viruses reveal an unanticipated antiviral activity for miR-146a. J Gen Virol. 2013;94(Pt 5):985-995.
97. Hofstetter G, Berger A, Berger R, et al. The N-terminally truncated p53 isoform Delta40p53 influences prognosis in mucinous ovarian cancer. Int J Gynecol Cancer. Mar 2012;22(3):372-379.
98. Hofstetter G, Berger A, Schuster E, et al. Delta133p53 is an independent prognostic marker in p53 mutant advanced serous ovarian cancer. Br J Cancer. 2011;105(10):1593-1599.
99. Anensen N, Hjelle SM, Van Belle W, et al. Correlation analysis of p53 protein isoforms with NPM1/FLT3 mutations and therapy response in acute myeloid leukemia. Oncogene. 2012;31(12):1533-1545.
100. Selivanova G, Wiman KG. Reactivation of mutant p53: molecular mechanisms and therapeutic potential. Oncogene. 2007;26(15): 2243-2254.
101. Vassilev LT, Vu BT, Graves B, et al. In vivo activation of the p53 pathway by small-molecule antagonists of MDM2. Science. 2004;303(5659):844-848.
102. Dutertre M, Sanchez G, Barbier J, Corcos L, Auboeuf D. The emerging role of pre-messenger RNA splicing in stress responses: sending alternative messages and silent messengers. RNA Biol. 2011;8(5):740-747.
103. Grover R, Ray PS, Das S. Polypyrimidine tract binding protein regulates IRES-mediated translation of p53 isoforms. Cell Cycle. 2008;7(14):2189-2198.
104. Montanaro L, Calienni M, Bertoni S, et al. Novel dyskerin-mediated mechanism of p53 inactivation through defective mRNA translation. Cancer Res. 2010;70(11):4767-4777.
105. Sharathchandra A, Lal R, Khan D, Das S. Annexin A2 and PSF proteins interact with p53 IRES and regulate translation of p53 mRNA. RNA Biol. 2012;9(12):1429-1439.
106. Weingarten-Gabbay S, Khan D, Liberman N, et al. The translation initiation factor DAP5 promotes IRES-driven translation of p53 mRNA. Oncogene. Epub January 14, 2013.
107. Camus S, Ménendez S, Fernandes K, et al. The p53 isoforms are differentially modified by Mdm2. Cell Cycle. 2012;11(8):1646-1655.
108. Secchiero P, Bosco R, Celeghini C, Zauli G. Recent advances in the therapeutic perspectives of Nutlin-3. Curr Pharm Des. 2011;17(6): 569-577.