Нарушения в системе белка р53 и их влияние на патогенез хронических лимфопролиферативных заболеваний
Аннотация
В настоящее время активно обсуждается роль белков семейства р53 как в рамках патогенеза хронических лимфопролиферативных заболеваний, так и в свете растущего интереса к терапевтическому потенциалу так называемых малых молекул, способных влиять на регуляторные «взаимоотношения» молекул р53, MDM2, p21 и PUM A. Представленная статья является попыткой обобщить данные экспериментальных моделей на тканях опухоли и мышиных моделях и доступных в литературе исследований с использованием материала лимфоидных опухолей человека. Рассмотрены как аспекты прогностической значимости экспрессии белков семейства р53 при лимфопролиферативных заболеваниях, так и возможные терапевтические подходы, использующие
особенности взаимоотношений р53-молекулы с генами-регуляторами и эффекторами.
Ключевые слова
хронические лимфопролиферативные заболевания,
лимфомы,
хронический лимфолейкоз,
апоптоз,
р53,
MDM2,
p21,
PUMA
Об авторах
П. М. Кондратовский
Владивостокский государственный медицинский университет
Россия
Россия
А. И. Дубиков
Владивостокский государственный медицинский университет
Россия
Россия
А. Ю. Дорошевская
Владивостокский государственный медицинский университет
Россия
Россия
Список литературы
1. Новиков B.C. Программированная клеточная гибель. СПб.: «Наука», 1996.
2. Hansen R., Oren M. P53 from inductive signal to cellular effect. Curr Opin Genet 1997;7:46–51.
3. Bakhshi A.J., Jensen P., Goldman P. et al. Cloning the chromosomal breakpoint of t(14;18) human lymphomas: clustering around JH on chromosome 14 and near a transcriptional unit on 18. Cell 1985;41:889–906.
4. Tsujimoto Y., Gorham J., Cossman J. et al. The t(14;18) chromosome translocations involved in B-cell neoplasms result from mistakes in VDJ joining. Science 1985;229:1390–3.
5. Deary M., Smith S., Sclar J. Cloning and structional analysis of cDNAs Bcl-2 and a hybrid Bcl-2/immunoglobulin transcript resulting from the t(14;18) translocation. Cell 1986;47:19–23.
6. Kelekar Т., Thompson C. Bcl-2 family proteins: the role of the BH3 domain in apoptosis. Trends Cell Biol 1998;8:324–30.
7. Puthalakath H., Huang D., OʼReily L. et al. The proapoptotic activity of the Bcl-2 family member Bim is regulated by interaction with the dynein motor complex. Mol Cell 1999;3:287–96.
8. Oltvai Z., Korsmeyer S. Checkpoints of dueling dimers foil death wishes. Cell 1994;79:189–92.
9. Bellido M., Capello D., Altes A. et al. Bcl-6 p53 mutations in lymphomas carrying the Bcl-2/Jh rearrangement. Haematologica 2002;87(9):908–17.
10. Scorpa A., Moore P.S., Rigaurd G. et al. Molecular features of primary mediastinal B-cell lymphoma: involvement of p16INK4A, p53 and c-myc. Br J Haematol 1999;107(1):106–13.
11. Gaidano G., Volpe G., Pastore C. et al. Detection of BCL-6 rearrangements and p53 mutations in MALT-lymphomas. Am J Hematol 1997;56(4):206–13.
12. Petit B., Leroy K., Kanavaros P. et al. Expression of p53 protein in T- and natural killer-cell lymphomas is associated with some clinicopathologic entities but rarely related to p53 mutations. Hum Pathol 2001 Feb;32(2):196–204.
13. Kapur S., Tiemann M., Menke M.A. et al. The role of p53 and anaplastic lymphoma kinase genes in the progression of cutaneous CD30(+) lymphoproliferative diseases. Indian J Med Res 2005 Jan;121(1):46–54.
14. Поддубная И.В. Лимфосаркома желудочно-кишечного тракта (клиника, диагностика, лечение). Автореф. дис. …докт. мед. наук. М., 1985.
15. Gruszka-Westwood A.M., Hamoudi R.A., Matutes E. et al. P53 abnormalities in splenic lymphoma with villous lymphocytes. Blood 2001 Jun 1;97(11):3552–8.
16. Greiner T.C., Moynihan M.J., Chan W.C. et al. P53 mutations in mantle cell lymphoma are associated with variant cytology and predict a poor prognosis. Blood 1996 May 15;87(10):4302–10.
17. Sander C.A., Yano T., Clark H.M. et al. P53 mutation is associated with progression in follicular lymphomas. Blood 1993 Oct 1;82(7):1994–2004.
18. Villuendas R., Piris M.A., Orradre J.L. et al. P53 protein expression in lymphomas and reactive lymphoid tissue. J Pathol 1992 Mar;166(3):235–41.
19. Cordone I., Masi S., Mauro F.R. et al. P53 expression in B-cell chronic lymphocytic leukemia: a marker of disease progression and poor prognosis. Blood 1998 Jun 1;91(11):4342–9.
20. Yu J., Zhang L. No PUMA, no death: implications for p53-dependent apoptosis. Cancer Cell 2003;4:248–9.
21. Michalak E.M., Villunger A., Adams J.M. et al. In several cell types tumour suppressor p53 induces apoptosis largely via Puma but Noxa can contribute. Cell Death Differ 2008;15:1019–29.
22. Garrison S.P., Jeffers J.R., Yang C. et al. Selection against PUMA gene expression in Myc-driven B cell lymphomagenesis. Mol Cell Biol 2008;28:5391–402.
23. Labi V., Erlacher M., Krumschnabel G. et al. Apoptosis of leukocytes triggered by acute DNA damage promotes lymphoma formation. Genes Dev 2010 August 1; 24:1602–7; oi:10.1101/gad.1940210.
24. Michalak E.M., Vandenberg C.J., Delbridge A.R., Wu L., Scott C.L., Adams J.M., Strasser A. Apoptosis-promoted tumorigenesis: gamma-irradiation-induced thymic lymphomagenesis requires Pumadriven leukocyte death. Genes Dev 2010August 1;24:1608–13; doi:10.1101/gad.1940110.
25. Zhu H.J., Xu W., Cao X. et al. Detection of puma mRNA levels by real-time quantitative RT-PCR in chronic lymphocytic leukemia and its clinical significance. Zhongguo Shi Yan Xue Ye Xue Za Zhi 2010 Aug;18(4):843–8.
26. Mackus W.J., Kater A.P., Grummels A. et al. Chronic lymphocytic leukemia cells display p53-dependent drug-induced Puma upregulation. Leukemia 2005 Mar;19(3):427–34.
27. El-Deiry W.S. Regulation of p53 downstream genes. Semin Cancer Biol 1998;8:345–57.
28. Deng Y., Chan S.S., Chang S. Telomere dysfunction and tumour suppression: the senescence connection. Nat Rev Cancer 2008;8:450–8.
29. Halazonetis T.D., Gorgoulis V.G., Barteck J. An oncogene-induced DNA damage model for cancer development. Science 2008;319:1352–5.
30. Martins C.P., Brown-Swigart L., Evan G.I. Modeling the therapeutic efficacy of p53 restoration in tumors. Cell 2006;127:1323–34.
31. Ventura A., Xu G., Wang H. et al. Expressions of p53 and p21 in nasal NK/ T-cell lymphoma and their relationship with the proliferation and apoptosis of cells. Lin Chung Er Bi Yan Hou Tou Jing Wai Ke Za Zhi 2009 Jan;23(2):73–6.
32. Xue W., Zender L., Miething C. et al. Senescence and tumour clearance is triggered by p53 restoration in murine liver carcinomas. Nature 2007;445:656–60.
33. Brown J.P., Wei W., Sedivy J.M. Bypass of senescence after disruption of p21CIP1/ WAF1 gene in normal diploid human fibroblasts. Science 1997;277:831–4.
34. Cosme-Blanco W., Shen M.F., Lazar A.J.F. et al. Telomere dysfunction suppresses spontaneous tumorigeesis in vivo by initiating p53-dependent cellular senescence. EMBO Rep 2007;8:497–503.
35. Van Nguyen T., Puebla-Osorio N., Pang H. et al. DNA damage-induced cellular senescence is sufficient to suppress tumorigenesis: a mouse model. J Exp Med 2007;204:1453–61.
36. Barboza J.A., Liu G., El-Naggar A.K. et al. p21 delays tumor onset by preservation of chromosomal stability. Proc Natl Acad Sci USA 2006;103:19842–7.
37. De la Cueva E., García-Cao I., Herranz M. et al. Tumorigenic activity of p21Waf1/Cip1 in thymic lymphoma. Oncogene 2006 Jul 6;25(29):4128–32. Epub 2006 Feb 6. 38. Chilosi M., Doglioni C., Magalini A. et al. p21/WAF1 cyclin-kinase inhibitor expression in non-Hodgkin's lymphomas: a potential marker of p53 tumor-suppressor gene function. Blood 1996 Nov 15; 88(10):4012–20.
38. Xu G., Wang H., He G. et al. Expressions of p53 and p21 in nasal NK/T-cell lymphoma and their elationship with the proliferation and apoptosis of cells. Lin Chung Er Bi Yan Hou Tou Jing Wai Ke Za Zhi 2009 Jan;23(2):73–6.
39. Go J.H., Yang W.I. Expressions of p53 and p21 in primary gastric lymphomas. J Korean Med Sci 2001 Dec;16(6):731–5.
40. Marine J.C., Francoz S., Maetens M. et al. Keeping p53 in check: essential and synergistic functions of MDM2 and MDM4. Cell Death Differ 2006;13:927–34.
41. Marine J.C., Dyer M.A., Jochemsen A.G. MDMX: from bench to bedside. J Cell Sci 2007;120:371–8.
42. Poyurovsky M.V., Prives C. Unleashing the power of p53: lessons from mice and men. Genes Dev 2006;20:125–31.
43. Toledo F.G., Wahl M. Regulating the p53 pathway: in vitro hypotheses, in vivo veritas. Nat Rev Cancer 2006;6:909–23.
44. Itahana K., Mao H., Jin A. et al. Targeted inactivation of MDM2 RING finger E3 ubiquitin ligase activity in the mouse reveals mechanistic insights into p53 regulation. Cancer Cell 2007;12:355–66.
45. Ito A., Lai C.H., Zhao X. et al. p300/CBP-mediated p53 acetylation is commonly induced by p53-activating agents and inhibited by MDM2. EMBO J 2001;20:1331–40.
46. Teufel D.P., Freund S.M., Bycroft M. et al. Four domains of p300 each bind tightly to a sequence spanning both transactivation subdomains of p53. Proc Natl Acad Sci USA 2007;104:7009–14.
47. Ohkubo S., Tanaka T., Taya Y. et al. Excess HDM2 impacts cell cycle and apoptosis and has a selective effect on p53-dependent transcription. J Biol Chem 2006;281:16943–50.
48. Tang Y., Zhao W., Chen Y., et al. Acetylation is indispensable for p53 activation. Cell 2008;133:612–26.
49. Minsky N., Oren M. The RING domain of Mdm2 mediates histone ubiquitylation and transcriptional repression. Mol Cell 2004;16:631–9.
50. Tzardi M., Kouvidou Ch., Panayiotides I. et al. p53 protein expression in non- Hodgkin's lymphoma. Comparative study with the wild type p53 induced proteins MDM2 and p21/waf1. Clin Mol Pathol 1996 Oct;49(5):278–82.
51. Stefanaki K., Tzardi M., Kouvidou C. et al. Expression of p53, p21, MDM2, Rb, Bax and Ki67 proteins in lymphomas of the mucosa-associated lymphoid (MALT) tissue. Anticancer Res 1998 Jul–Aug; 18(4A):2403–8.
52. Camacho F.I., Bellas C., Corbacho C. et al. Improved demonstration of immunohistochemical prognostic markers for survival in follicular lymphoma cells. Mod Pathol 2011 May;24(5):698–707. Epub 2011 Jan 14.
53. Wang P., Lushnikova T., Odvody J. et al. Elevated MDM2 expression induces chromosomal instability and confers a survival and growth advantage to B cells. Oncogene 2008 Mar 6;27(11):1590–8.
54. Cui Y.X., Kerby A., McDuff F.K. et al. NPM-ALK inhibits the p53 tumor suppressor pathway in an MDM2 and JNK-dependent manner. Blood 2009 May 21;113(21):5217–27.
55. Kojima K., Konopleva M., McQueen T. et al. MDM2 inhibitor Nutlin-3a induces p53-mediated apoptosis by transcriptiondependent and transcription-independent mechanisms and may overcome Atmmediated resistance to fludarabine in chronic lymphocytic leukemia. Blood 2006 August 1; 108(3):993–1000.
56. Senzer N., Nemunaitis J. A review of contusugene ladenovec (Advexin) p53 therapy. Curr Opin Mol Ther 2009;11:54–61.
57. Lain S., Hollick J.J., Campbell J. et al. Discovery, in vivo activity, and mechanism of action of a small-molecule p53 activator. Cancer Cell 2008;13:454–63.
58. Ringshausen I., O’Shea C.C., Finch A.J. et al. MDM2 is critically and continuously required to suppress lethal p53 activity in vivo. Cancer Cell 2006;10:501–14.
59. Brummelkamp T.R., Fabius A.W., Mullenders J. et al. An shRNA barcode screen provides insight into cancer cell vulnerability to MDM2 inhibitors. Nat Chem Biol 2006;2:202–6.
60. Selivanova G., Wiman K.G. Reactivation of mutant p53: molecular mechanisms and therapeutic potential. Oncogene 2007;26:2243–54.
61. Drakos E., Atsaves V., Li J. et al. Stabilization and activation of p53 downregulates mTOR signaling through AMPK in mantle cell lymphoma. Leukemia 2009 Apr;23(4):784–90.
62. Jin L., Tabe Y., Kojima K. et al. MDM2 antagonist Nutlin-3 enhances bortezomibmediated mitochondrial apoptosis in TP53- mutated mantle cell lymphoma. Cancer Lett 2010 Dec 28;299(2):161–70.
63. Tabe Y., Sebasigari D., Jin L. et al. DM2 antagonist nutlin-3 displays antiproliferative and proapoptotic activity in mantle cell lymphoma. Clin Cancer Res 2009 Feb 1;15(3):933–42.
64. Drakos E., Atsaves V., Schlette E. et al. The therapeutic potential of p53 reactivation by nutlin-3a in ALK+ anaplastic large cell lymphoma with wild-type or mutated p53. Leukemia 2009 Dec;23(12):2290–9.
65. Coll-Mulet L., Iglesias-Serret D., Santidrián A.F. et al. MDM2 antagonists activate p53 and synergize with genotoxic drugs in B-cell chronic lymphocytic leukemia cells. Blood 2006 May 15; 107(10):4109–14.
66. Mohammad R.M., Wu J., Azmi A.S. et al. An MDM2 antagonist (MI-319) restores p53 functions and increases the life span of orally treated follicular lymphoma bearing animals. Mol Cancer 2009 Dec 3;8:115.
67. Jones R.J., Chen Q., Voorhees P.M. et al. Inhibition of the p53 E3 ligase HDM-2 induces apoptosis and DNA damage —independent p53 phosphorylation in mantle cell lymphoma. Clin Cancer Res 2008 Sep 1;14(17):5416–25.
68. Petitjean A., Achatz M.I., Borresen-Dale A.L. et al. TP53 mutations in human cancers: functional selection and impact on cancer prognosis and outcomes. Oncogene 2007;26:2157–65.
69. Bertheau P., Espie M., Turpin E. et al. TP53 status and response to chemotherapy in breast cancer. Pathobiology 2008; 75:132–9.
70. Sur S., Pagliarini R., Bunz F. et al. A panel of isogenic human cancer cells suggests a therapeutic approach for cancers with inactivated p53. Proc Natl Acad Sci USA 2009;106:3964–9.
71. Carvajal D., Tovar C., Yang H. et al. Activation of p53 by MDM2 antagonists can protect proliferating cells from mitotic inhibitors. Cancer Res 2005;65:1918–24.
72. Kranz D., Dobbelstein M. Nongenotoxic p53 activation protects cells against S-phasespecific chemotherapy. Cancer Res 2006;66:10274–80.
73. Gudkov A.V., Komarova E.A. Prospective therapeutic applications of p53 inhibitors. Biochem Biophys Res Commun 2005;331:726–36.
74. Strom E., Sathe S., Komarov P.G. et al. Small-molecule inhibitor of p53 binding to mitochondria protects mice from gamma radiation. Nat Chem Biol 2006;2:474–9.
Для цитирования:
Кондратовский П.М., Дубиков А.И., Дорошевская А.Ю. Нарушения в системе белка р53 и их влияние на патогенез хронических лимфопролиферативных заболеваний. Онкогематология. 2011;6(3):65-75. https://doi.org/10.17650/1818-8346-2011-6-3-65-75
For citation:
Kondratovskiy P.M., Dubikov A.I., Doroshevskaya A.Y. P53 pathway changes and their influence on chronic lymphoproliferative diseases pathogenesis. Oncohematology. 2011;6(3):65-75. (In Russ.) https://doi.org/10.17650/1818-8346-2011-6-3-65-75
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