CASP8、Fas和FasL基因多态与外周T细胞淋巴瘤易感性及临床特点和预后的相关性研究
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摘要
CASP8、Fas和FasL基因多态与外周T细胞淋巴瘤易感性及临床特点和预后的相关性研究
     Fas-Fasl介导的细胞凋亡是经典的免疫细胞死亡机制,对于免疫自稳具有重要的作用,如果异常可导致疾病的发生,如肿瘤的发生。本研究主要探讨Fas、FasL和凋亡相关的半胱氨酸蛋白酶8 (CASP-8)的遗传变异与外周T细胞淋巴瘤(peripheral T-cell lymphoma, PTCL)发生的关系,以及Fas和CASP-8基因多态性与PTCL的临床特点和预后的关系。首先采用病例对照的方法分析了100例外周T细胞淋巴瘤和544例正常对照者Fas[-1377G→■T (rs1377)和-670A→G(rs670)]、FasL[-844T→C (rs844)]和CASP8启动子区-652 AGTAAG插入/缺失(-6526N ins/del, rs3834129)基因多态与PTCL易感性的关系,比值比(Odds,OR)和95%可信区间(confidence intervals, CI)用来评价易感性强弱,统计方法采用logistic regression,且所有统计都是双侧检验,P<0.05有意义。我们发现Fas和CASP8的基因多态性和PTCL的易感性相关,而FasL的基因多态性则与PTCL的易感性不相关。与携带Fas-1377GG基因型相比,携带Fas-1377AA基因型的PTCL患病风险降低,OR值为0.48(95%CI0.23-0.99,p=0.049);与携带CASP8-6526N ins/ins基因型相比,携带CASP8-6526N ins/del基因型个体PTCL的患病风险增高,OR值为1.84(95%CI 1.18-2.87,p=0.007);而Fas-670 A>G和FasL-844T> C的基因多态性与PTCL的易感性不相关。本研究同时分析了304例B细胞淋巴瘤与476例正常对照者Fas (-1377>T和-670A>G)、FasL (-844T>C)和CASP8 (-6526N ins/del)基因多态与B细胞淋巴瘤易感性的关系,我们发现,Fas和FasL基因多态性与B细胞淋巴瘤易感性相关。与携带Fas-1377GG基因型相比,携带Fas-1377GA基因型个体患B细胞淋巴瘤的风险性降低,OR值为0.57(95 %CI0.41-0.77,p<0.001),与携带FasL-844CC基因型相比,携带FasL-844CT基因型的个体患B细胞淋巴瘤的风险增高,OR值为1.37(95% CI1.01-1.90,p=0.043);而Fas-670A>G和CASP8-6526N ins/del的基因多态性与B细胞淋巴瘤的易感性不相关。研究结果表明,CASP8-6526N ins/del是PTCL的易感因素,而FasL-844CT基因型是B细胞淋巴瘤的易感因素,Fas-1377AA和Fas-1377GA基因型分别是PTCL和B细胞淋巴瘤的保护性因素。根据CASP8和Fas基因多态性在PTCL中的研究结果,我们进一步采用相关性分析的方法分析CASP8和Fas基因多态性和89例PTCL的临床特点的关系,采用Kaplan-Meier统计方法分析CASP8和Fas基因多态性与89例PTCL患者预后的关系。除CASP8-6526N ins/del基因多态性在男性PTCL中更多见外(p=0.032), CASP8-6526N ins/del和Fas-1377G>A的基因多态性与PTCL的临床特点和预后均没有相关性。下一步我们需要扩大样本量继续研究它们的关系。
Genetic polymorphisms in CASP8, Fas and Fas ligand and the risk of peripheral T-cell lymphoma and the relationship between the genetic polymorphisms and the clinical characteristics and prognosis
     Fas-Fas ligand (FasL)-mediated cell apoptosis is a classic pathway of the immune cells death and is important for the immune homeostasis, if the function of the fas/fasL is impaired, which will result in disease, including carcinogenesis. Therefore this study examined the association between functional variants of Fas (-1377G>A and-670A>G), FasL (-844T>C), and caspase-8 (CASP8) six-nucleotide deletion polymorphism (-6526N ins-del) and risk of peripheral T-cell lymphoma(PTCL),also explored the relationship between the genetic polymorphisms in Fas and CASP8 and the clinical characteristics and prognosis. Genotypes of Fas, FasL and CASP8 were determined in 100 patients with PTCL and 544 frequency-matched controls. Odds ratios (OR) and 95%confidence intervals (95%CI) were estimated by logistic regression, and all statistical tests were two sided, p value must be less than 0.05.We found a significant correlation in risk of PTCL with Fas and CASP8 but not FasL polymorphisms. Compared with those with Fas-1377GG, the subjects with Fas-1377AA had a decreased risk for PTCL, OR=0.48(95%CI 0.23-0.99, p=0.049); Compared with those with the CASP8-6526N ins/ins genotype, the subjects with CASP8-6526N ins/del had an increased risk for T-cell lymphoma, OR=1.84 (95%CI 1.18-2.87, p=0.007). The genetic polymorphisms in Fas-670 A>G and FasL-844T> C had no correlationship with the risk of PTCL. We also investigated the association between genetic polymorphisms in Fas, FasL and CASP8 and B-cell lymphoma. We found that a significant correlation in risk of B-cell lymphoma with Fas and FasL but not CASP8 polymorphisms.Compared with those with Fas-1377GG, the subjects with Fas-1377GA had a decreased risk for B-cell lymphoma, OR=0.57 (95%CI 0.41-0.77, p<0.001); Compared with those with the FasL-844CC genotype, the subjects with FasL-844CT had an increased risk for B-cell lymphoma, OR=1.37 (95%CI 1.01-1.90, p=0.043). The genetic polymorphisms in Fas-670 A>G and CASP8-6526N ins/del had no correlationship with the risk of B-cell lymphoma. These data suggest that CASP8-6526N ins/del is associated with increased risk of PTCL, The FasL-844CT is associated with increased risk of B-cell lymphoma, and the Fas-1377GA and Fas-1377AA is a protective factor for B-cell lymphoma and PTCL respectively. Based on the relationship between the risk of PTCL and the genetic polymorphisms in Fas, FasL and CASP8. We further expored the the relationship between the genetic polymorphisms in Fas and CASP8 and the clinical characteristics and prognosis. Except that the CASP8-6526N ins/del genotype is more often in male than female (p=0.032),we couldn't find any subjects with relationship between the the genetic polymorphisms in Fas and CASP8 and the clinical characteristics and prognosis.We need a large number patients to find the true relationship of them.
引文
1. The Non-Hodgkin's Lymphoma Classification Project. A clinical evaluation of the International Lymphoma Study Group Classification of Non-Hodgkin's Lymphoma. Blood 1997; 89:3909-3918.
    2.尹洪芳,李挺,李竞贤.应用世界卫生组织淋巴组织肿瘤新分类对304例恶性淋巴瘤的重新评估,中华医学杂志,2003,83(18):1556-1560。
    3.肖畅,苏祖兰,吴秋良等.根据WHO新分类对493例非霍奇金淋巴瘤的临床病理分析. 中华病理学杂志,2005,34(1):22-27。
    4.周立强,孙燕,谭文勇等.非霍奇金淋巴瘤1125例临床病理分析.癌症进展,2006,4(5):391-397。
    5. International T-Cell Lymphoma Project. International peripheral T-cell and natural killer/T-cell lymphoma study:pathology findings and clinical outcomes. J Clin Oncol 2008,26:4124-4130.
    6. Armitage JO, Vose JM, Weisenburger DD. Towards understanding the peripheral T-cell lymphomas. Ann Oncol 2004,15(10):1447-1449.
    7. Ascani S, Zinzani PL, Gherlinzoni F, et al. Peripheral T-cell lymphomas. Clinico-pathologic study of 168 cases diagnosed according to the R.E.A.L. classification. Ann Oncol 1997,8(6):583-592.
    8. Arrowsmith ER, Macon WR, Kinney MC, et al. Peripheral T-cell lymphomas: clinical features and prognostic factors of 92 cases defined by the revised European American lymphoma classification. Leuk Lymphoma 2003,44(2):241-249.
    9. Savage KJ, Chhanabhai M, Gascoyne RD, Connors JM. Characterization of peripheral T-cell lymphomas in a single North American institution by the WHO classification. Ann Oncol 2004,15(10):1467-1475.
    10. Gallamini A, Stelitano C, Calvi R, et al. Peripheral T-cell lymphoma unspecified (PTCL-U):a new prognostic model from a retrospective multicentric clinical study. Blood 2004,103(7):2474-2479.
    11. Gisselbrecht C, Gaulard P, Lepage E, et al. Prognostic significance of T-cell phenotype in aggressive non-Hodgkin's lymphomas.Groupe d'Etudes des Lymphomes de l'Adulte (GELA).Blood 1998,92(1):76-82.
    12. Coiffier B, Brousse N, Peuchmaur M, et al. Peripheral T-cell lymphomas have a worse prognosis than B-cell lymphomas:a prospective study of 361 immunophenotyped patients treated with the LNH-84 regimen. The GELA (Groupe
    d'Etude desLymphomes Agressives). Ann Oncol 1990,1(1):45-50.
    13. Ansell SM, Habermann TM, Kurtin PJ, et al. Predictive capacity of the International Prognostic Factor Index in patients with peripheral T-cell lymphoma. J Clin Oncol 1997,15(6):2296-2301.
    14. Melnyk A, Rodriguez A, Pugh WC, Cabannillas F. Evaluation of the revised European-American lymphoma classification confirms the clinical relevance of immunophenotype in 560 cases of aggressive non-Hodgkin's lymphoma. Blood 1997,89(12):4514-4520.
    15. Ekstrom-Smedby K. Epidemiology and etiology of non-Hodgkin lymphoma-- a review. Acta Oncol 2006,45(3):258-271.
    16.Boldin M. P., Goncharov T. M., Goltsev Y. V. and Wallach D. (1996) Involvement of MACH, a novel MORT1:FADDinteracting protease, in Fas:APO-1-and TNF receptor-induced cell death. Cell 85:803-815.
    17. Muzio M., Chinnaiyan A. M., Kischkel F. C., O'Rourke K., Shevchenko A., Ni J. et al. (1996) FLICE, a novel FADDhomologous ICE:CED-3-like protease, is recruited to the CD95 (Fas:APO-1) death-inducing signaling complex. Cell 85:817-827.
    18. Kischkel FC, Hellbardt S, Behrmann I, Germer M, Pawlita M, Krammer PH, et al. Cytotoxicity-dependent APO-1 (Fas/CD95)-associated proteins form a death-inducing signaling complex (DISC) with the receptor. EMBO J 1995,14(22): 5579-5588.
    19. Lee SH, Shin MS, ParkWS, et al. Alterations of Fas(APO-1/CD95) gene in transitional cell carcinomas of urinary bladder. Cancer Res 1999,59:3068-3072.
    20. Mandruzzato S, Brasseur F, Andry G, BoonT, van der Bruggen P. A CASP-8 mutation recognized by cytolytic T lymphocytes on a human head and neck carcinoma. J Exp Med 1997,186:785-793.
    21. Kim HS, Lee JW, SoungYH, et al. Inactivatingmutations of caspase-8 gene in colorectal carcinomas. Gastroenterology2003,125:708-715.
    22. SoungYH, Lee JW, Kim SY, et al. CASPASE-8 gene is inactivated by somatic mutations in gastric carcinomas. Cancer Res 2005,65:815-821.
    23. Rabinowich H, Reichert TE, Kashii Y, Gastman BR,Bell MC,Whiteside TL. Lymphocyte apoptosis induced by Fas ligand-expressing ovarian carcinoma cells. Implications for altered expression of T cell receptor in tumor-associated lymphocytes. J Clin Invest 1998,101:2579-2588.
    24. O'Connell J, O'Sullivan GC, Collins JK, Shanahan F. The Fas counterattack: Fas-mediated T cell killing by colon cancer cells expressing Fas ligand. J Exp Med 1996,184:1075-1082.
    25. Crnogorac-JurcevicT, Efthimiou E, Capelli P, et al. Gene expression profiles of pancreatic cancer and stromal desmoplasia. Oncogene 2001,20:7437-7446.
    26. Huang QR, Morris D, Manolios N. Identification and characterization of polymorphisms in the promoter region of the human Apo-1/Fas (CD95) gene. Mol Immunol 1997,34:577-582.
    27. Sibley K, Rollinson S, AllanJM, et al. Functional FAS promoter polymorphisms are associated with increased risk of acute myeloid leukemia. Cancer Res 2003, 63:4327-4330.
    28. Wu J, Metz C, Xu X, et al. A novel polymorphic CAAT/enhancer-binding protein h element in the FasL gene promoter alters Fas ligand expression:a candidate background gene in African American systemic lupus erythematosus patients. J Immunol 2003,170:132-138.
    29. Ming Yang,1 Tong Sun,1 Li Wang Functional Variants in Cell Death Pathway Genes andRisk of Pancreatic Cancer.Clin Cancer Res 2008,14(10):3230-3236.
    30. Aalmena, L, Hakem, R. Caspase-8 deficiency in T cells leads to a lethal lymphoinfiltrative immune disorder. J. Exp. Med 2005,202:727-732.
    31. Sun T, Gao Y, Tan W, Ma S, Shi Y, Yao J, Guo Y, Yang M, Zhang X, Zhang Q, Zeng C, Lin DA six-nucleotide insertion-deletion polymorphism in the CASP8 promoter is associated with susceptibility to multiple cancers. Nat Genet.2007,39(5):605-613.
    32. Itoh N, Yonehara S, Ishii A, Yonehara M, Mizushima S, Sameshima M, et al. The polypeptide encoded by the cDNA for human cell surface antigen Fas can mediate apoptosis. Cell 1991,66:233-243.
    33. Pan G, O'Rourke K, Chinnaiyan AM, Gentz R, Ebner R, Ni J, et al. The receptor for the cytotoxic ligand TRAIL. Science 1997,276:111-113.
    34. Walczak H, Degli-Esposti MA, Johnson RS, Smolak PJ, Waugh JY, Boiani N, et al. TRAIL-R2:a novel apoptosis-mediating receptor for TRAIL. Embo J 1997,16: 5386-5397.
    35. Wiley SR, Schooley K, Smolak PJ, Din WS, Huang CP, Nicholl JK, et al. Identification and characterization of a new member of the TNF family that induces apoptosis. Immunity 1995,3:673-682.
    36. Schutze S, Tchikov V and Schneider-Brachert W. Regulation of TNFR1 and CD95 signalling by receptor compartmentalization. Nat Rev Mol Cell Biol 2008,9: 655-662.
    37. Schaefer U, Voloshanenko O, Willen D and Walczak H. TRAIL:a multifunctional cytokine. Front Biosci 2007,12:3813-3824.
    38. Falschlehner C, Schaefer U and Walczak H. Following TRAIL'S path in the immune system. Immunology 2009,127:145-154.
    39. Strasser A, Jost PJ and Nagata S. The many roles of FAS receptor signaling in the immune system. Immunity 2009,30:180-192.
    40. Bouillet P and O'Reilly LA. CD95, BIM and T cell homeostasis. Nat Rev Immunol 2009,9:514-519.
    41.Jaffe ES,Harris NL,Stein H, et al. World Health Organisation Classification of Tumours. Pathology and genetics of tumours of haematopoietic and lymphoid tissues. Lyon:IARC Press,2001
    42. Reiser M, Josting A, Soltani M, et al. T-cell non-Hodgkin's lymphoma in adults: clinicopathological characteristics, response to treatment and prognostic factors. Leuk Lymphoma,2002,43(4):805-811.
    43. Coiffier B, Berger F, Bryon PA, et al. T-cell lymphomas:immunologic, histologic, clinical and therapeutic analysis of 63 cases. J Clin Oncol,1988,6(10):1584-1589
    44. Liang R, Loke SL, Chan AC. The prognostic factors for peripheral T-cell lymphomas. Hematol Oncol,1992,10(3-4):135-140
    45. Rodriguez J, Cabanillas F, Mclaughlin P, et al. A proposal for a simple staging system for intermediate grade lymphoma and immunoblastic lymphoma based on the'tumor score'. Ann Oncol,1992,3(9):711-717
    46. Campo E, Gaulard P, Zucca E, et al. Report of the European Task Force on Lymphomas:Workshop on peripheral T-cell lymphomas. Annals of Oncology,1998, 9(8):835-843
    47. Vose JM, The International PP. International Peripheral T-Cell Lymphoma (PTCL)Clinical and Pathologic Review Project:Poor Outcome by Prognostic Indices and Lack of Efficacy with Anthracyclines, ASH Annual Meeting Abstracts,2005,106(11):811
    1. Lamkanfi M, Festjens N, Declercq W, Vanden Berghe T, Vandenabeele P. Caspases in cell survival, proliferation and differentiation. Cell Death Differ 2007,14(1):44-55.
    2. Kumar S. Caspase function in programmed cell death. Cell Death Differ 2007,14(1):32-43.
    3. Riedl SJ, Salvesen GS. The apoptosome:signalling platform of cell death. Nat Rev Mol Cell Biol 2007,8(5):405-413.
    4. Mariathasan S, Monack DM. Inflammasome adaptors and sensors:intracellular regulators of infection and inflammation. Nat Rev Immunol 2007,7(1):31-40.
    5. Peter ME, Krammer PH. The CD95(APO-1/Fas) DISC and beyond. Cell Death Differ 2003,10(1):26-35.
    6. Varfolomeev EE, Schuchmann M, Luria V, Chiannilkulchai N, Beckmann JS, Mett IL, et al. Targeted disruption of the mouse caspase 8 gene ablates cell death induction by the TNF receptors, Fas/Apol, and DR3 and is lethal prenatally. Immunity 1998, 9(2):267-276.
    7. Sakamaki K, Inoue T, Asano M, Sudo K, Kazama H, Sakagami J, et al. Ex vivo whole-embryo culture of caspase-8-deficient embryos normalize their aberrant phenotypes in the developing neural tube and heart. Cell Death Differ 2002, 9(11):1196-1206.
    8. Kang TB, Ben-Moshe T, Varfolomeev EE, Pewzner-Jung Y,Yogev N, Jurewicz A, et al. Caspase-8 serves both apoptotic and nonapoptotic roles. J Immunol 2004, 173(5):2976-2984.
    9. Salmena L, Lemmers B, Hakem A, Matysiak-Zablocki E, Murakami K, Au PY, et al. Essential role for caspase 8 in Tcell homeostasis and T-cell-mediated immunity. Genes Dev 2003,17(7):883-895.
    10. Beisner DR, Ch'en IL, Kolla RV, Hoffmann A, Hedrick SM.Cutting edge:innate immunity conferred by B cells is regulated by caspase-8. J Immunol 2005, 175(6):3469-3473.
    11. Lemmers B, Salmena L, Bidere N, Su H, Matysiak-Zablocki E, Murakami K, et al. Essential role for caspase-8 in toll-like receptors and NFkappaB signaling. J Biol Chem 2007,282(10):7416-7423.
    12. Ben Moshe T, Barash H, Kang TB, Kim JC, Kovalenko A,Gross E, et al. Role of caspase-8 in hepatocyte response to infection and injury in mice. Hepatology 2007, 45(4):1014-1024.
    13. Boldin M. P., Goncharov T. M., Goltsev Y. V. and Wallach D. Involvement of MACH, a novel MORT1:FADDinteracting protease, in Fas:APO-1-and TNF receptor-induced cell death. Cell 1996,85:803-815.
    14. Muzio M., Chinnaiyan A. M., Kischkel F. C., O'Rourke K., Shevchenko A., Ni J. et al. FLICE, a novel FADDhomologous ICE:CED-3-like protease, is recruited to the CD95 (Fas:APO-1) death-inducing signaling complex. Cell 1996,85:817-827.
    15. Kischkel FC, Hellbardt S, Behrmann I, Germer M, Pawlita M, Krammer PH, et al. Cytotoxicity-dependent APO-1 (Fas/CD95)-associated proteins form a death-inducing signaling complex (DISC) with the receptor. EMBO J 1995,14(22): 5579-5588.
    16. Luo X, Budihardjo I, Zou H, Slaughter C, Wang X. Bid, a Bcl2 interacting protein, mediates cytochrome c release from mitochondria in response to activation of cell surface death receptors. Cell 1998,94(4):481-490.
    17. Fisher GH, Rosenberg FJ, Straus SE, Dale JK, Middleton LA, Lin AY, et al. Dominant interfering Fas gene mutations impair apoptosis in a human autoimmune lymphoproliferative syndrome. Cell 1995,81(6):935-946.
    18. Rieux-Laucat F, Le Deist F, Hivroz C, Roberts IA, Debatin KM, Fischer A, et al. Mutations in Fas associated with human lymphoproliferative syndrome and autoimmunity. Science 1995,268(5215):1347-1349.
    19. Wu J, Wilson J, He J, Xiang L, Schur PH, Mountz JD. Fas ligand mutation in a patient with systemic lupus erythematosus and lymphoproliferative disease. J Clin Invest 1996,98(5):1107-1113.
    20. Wang J, Zheng L, Lobito A, Chan FK, Dale J, Sneller M, et al. Inherited human caspase 10 mutations underlie defective lymphocyte and dendritic cell apoptosis in autoimmune lymphoproliferative syndrome type Ⅱ. Cell 1999,98(1):47-58.
    21. Chun HJ, Zheng L, Ahmad M, Wang J, Speirs CK, Siegel RM, et al. Pleiotropic defects in lymphocyte activation caused by caspase-8 mutations lead to human immunodeficiency. Nature 2002,419(6905):395-399
    22. Kennedy NJ, Kataoka T, Tschopp J, Budd RC. Caspase activation is required for T cell proliferation. J Exp Med 1999,190(12):1891-1896.
    23. Alam A, Cohen LY, Aouad S, Sekaly RP. Early activation of caspases during T lymphocyte stimulation results in selective substrate cleavage in nonapoptotic cells. J Exp Med 1999,190(12):1879-1890.
    24. Su H, Bidere N, Zheng L, Cubre A, Sakai K, Dale J, Salmena L, Hakem R, Straus S,Lenardo M. Requirement for caspase-8 in NF-kappaB activation by antigen receptor. Science 2005,307:1465-1468.
    25. Newton, K., Harris, A.W., Bath, M.L., Smith, K.G.C., and Strasser, A. A dominant interfering mutant of FADD/Mortl enhances deletion of autoreactive thymocytes and inhibits proliferation of mature T lymphocytes. EMBO J 1998,17:706-718.
    26. Smith, K.G.C., Strasser, A., and Vaux, D.L. CrmA expression in T lymphocytes of transgenic mice inhibits CD95 Fas/APO-1)-transduced apoptosis, but does not cause lymphadenopathy or autoimmune disease. EMBO J 1996,15:5167-5176.
    27. Walsh, C.M., Wen, B.G., Chinnaiyan, A.M., O'Rourke, K., Dixit, V.M., and Hedrick, S.M. A role for FADD in T cell activation and development. Immunity 1998,8:439-449.
    28. Arechiga AF, Bell BD, Solomon JC, Chu IH, Dubois CL, Hall BE, et al. Cutting edge:FADD is not required for antigen receptor-mediated NF-kappaB activation. J Immunol 2005,175(12):7800-7804.
    29. Newton, K., Kurts, C., Harris, A.W., and Strasser, A. Effects of a dominant interfering mutant of FADD on signal transduction in activated T cells. Curr. Biol 2001,11:273-276
    30. Hayden MS, Ghosh S. Signaling to NF-kappaB. Genes Dev 2004,18:2195-224.
    31. Li Q, Verma IM. NF-kappaB regulation in the immune system. Nat Rev Immunol 2002,2:725-734.
    32. Chu, D. H., Morita, C. T. and Weiss, A. The Syk family of protein tyrosine kinases in T-cell activation and development. Immunol. Rev 1998,165:167-180.
    33. Lucas, J. A., Miller, A. T., Atherly, L. O. and Berg, L. J. The role of Tec family kinases in T cell development and function. Immunol. Rev 2003,191:119-138.
    34. Zamoyska, R., Basson, A., Filby, A., Legname, G., Lovatt, M. and Seddon, B. The influence of the src-family kinases, Lck and Fyn, on T cell differentiation, survival and activation. Immunol. Rev 2003,191:107-118.
    35. Acuto, O., Mise-Omata, S., Mangino, G. and Michel, F. Molecular modifiers of T cell antigen receptor triggering threshold:the mechanism of CD28 costimulatory receptor. Immunol. Rev 2003,192:21-31.
    36. Isakov, N. and Altman, A. Protein kinase C(theta) in T cell activation. Annu. Rev. Immunol 2002,20:761-794.
    37. Baier, G., Telford, D., Giampa, L., Coggeshall, K. M., Baier-Bitterlich, G.,Isakov, N. and Altman, A. Molecular cloning and characterization of PKC theta, a novel member of the protein kinase C (PKC) gene family expressed predominantly in hematopoietic cells. J. Biol. Chem 1993,268:4997-5004.
    38. Chang, J. D., Xu, Y., Raychowdhury, M. K. and Ware, J. A. Molecular cloning and expression of a cDNA encoding a novel isoenzyme of protein kinase C (nPKC). A new member of the nPKC family expressedin skeletal muscle, megakaryoblastic cells, and platelets. J. Biol. Chem 1993,268:14208-14214.
    39. Osada, S., Mizuno, K., Saido, T. C., Suzuki, K., Kuroki, T. and Ohno, S. A new member of the protein kinase C family, nPKC theta, predominantly expressed in skeletal muscle. Mol. Cell. Biol 1992,12:3930-3938.
    40. Lin, X., O'Mahony, A., Mu, Y., Geleziunas, R. and Greene, W. C. Protein kinase C-theta participates in NF-kappaB activation induced by CD3-CD28 costimulation through selective activation of IkappaB kinase beta. Mol. Cell. Biol 2000,20: 2933-2940.
    41. Sun, Z., Arendt, C. W., Ellmeier, W., Schaeffer, E. M., Sunshine, M. J., Journal of Cell Science 117 (1) NF-kB signaling in lymphocytes 39 Gandhi, L., Annes, J., Petrzilka, D., Kupfer, A., Schwartzberg, P. L. et al. PKC-theta is required for TCR-induced NF-kappaB activation in mature but not immature T lymphocytes. Nature 2000,404:402-407.
    42. Ruland, J., Duncan, G. S., Elia, A., del Barco Barrantes, I., Nguyen, L.,Plyte, S., Millar, D. G., Bouchard, D., Wakeham, A., Ohashi, P. S. et al. Bcl10 is a positive regulator of antigen receptor-induced activation of NF-kappaB and neural tube closure. Cell 2001,104:33-42.
    43. Costanzo, A., Guiet, C. and Vito, P. c-E10 is a aspase-recruiting domain-containing protein that interacts with components of death receptors signaling pathway and activates nuclear factor-kappaB. J. Biol. Chem 1999,274:20127-20132.
    44. Koseki, T., Inohara, N., Chen, S., Carrio, R., Merino, J., Hottiger, M. O., Nabel, G. J. and Nunez, G. CIPER, a novel NF kappaB-activating protein containing a caspase recruitment domain with homology to Herpesvirus-2 protein E10. J. Biol. Chem 1999, 274:9955-9961.
    45. Srinivasula, S. M., Ahmad, M., Lin, J. H., Poyet, J. L., Fernandes-Alnemri, T., Tsichlis, P. N. and Alnemri, E. S. CLAP, a novel caspase recruitment domain-containing protein in the tumor necrosis factor receptor pathway, regulates NF-kappaB activation and apoptosis. J. Biol. Chem 1999,274:17946-17954.
    46. Thome, M., Martinon, F., Hofmann, K., Rubio, V., Steiner, V., Schneider, P., Mattmann, C. and Tschopp, J. Equine herpesvirus-2 E10 gene product, but not its cellular homologue, activates NF-kappaB transcription factor and c-Jun N-terminal kinase. J. Biol. Chem 1999,274:9962-9968.
    47. Willis, T. G., Jadayel, D. M., Du, M. Q., Peng, H., Perry, A. R., Abdul-Rauf, M., Price, H., Karran, L., Majekodunmi, O., Wlodarska, I. et al. Bcl10 is involved in t(1;14)(p22;q32) of MALT B cell lymphoma and mutated in multiple tumor types. Cell 1999,96:35-45.
    48. Yan, M., Lee, J., Schilbach, S., Goddard, A. and Dixit, V. mE10, a novel caspase recruitment domain-containing proapoptotic molecule. J.Biol. Chem 1999,274: 10287-10292.
    49. Zhang, Q., Siebert, R., Yan, M., Hinzmann, B., Cui, X., Xue, L.,Rakestraw, K. M., Naeve, C. W., Beckmann, G., Weisenburger, D. D. et al. Inactivating mutations and overexpression of BCL10, a caspase recruitment domain-containing gene, in MALT lymphoma with t(1;14)(p22;q32). Nat. Genet 1999,22:63-68.
    50. Akagi, T., Motegi, M., Tamura, A., Suzuki, R., Hosokawa, Y., Suzuki, H.,Ota, H., Nakamura, S., Morishima, Y., Taniwaki, M. et al. A novel gene, MALT1 at 18q21, is involved in t(11;18) (q21;q21) found in low-grade B-cell lymphoma of mucosa-associated lymphoid tissue. Oncogene 1999,18:5785-5794.
    51. Dierlamm, J., Baens, M., Wlodarska, I., Stefanova-Ouzounova, M.,Hernandez, J. M., Hossfeld, D. K., de Wolf-Peeters, C, Hagemeijer, A.,van den Berghe, H. and Marynen, P. The apoptosis inhibitor gene API2 and a novel 18q gene, MLT, are recurrently rearranged in the t(11;18)(q21;q21)p6ssociated with mucosa-associated lymphoid tissue lymphomas. Blood 1999,93,:3601-3609.
    52. Morgan, J. A., Yin, Y., Borowsky, A. D., Kuo, F., Nourmand, N., Koontz, J. I., Reynolds, C, Soreng, L., Griffin, C. A., Graeme-Cook, F. et al. Breakpoints of the t(11;18)(q21;q21) in mucosa-associated lymphoid tissue (MALT) lymphoma lie within or near the previously undescribed gene MALT1 in chromosome 18. Cancer Res 1999,59:6205-6213.
    53. Uren, A. G., O'Rourke, K., Aravind, L. A., Pisabarro, M. T., Seshagiri, S., Koonin, E. V. and Dixit, V. M. Identification of paracaspases and metacaspases:two ancient families of caspase-like proteins, one of which plays a key role in MALT lymphoma. Mol. Cell 2000,6:961-967.
    54. Lucas, P. C., Yonezumi, M., Inohara, N., McAllister-Lucas, L. M., Abazeed, M. E., Chen, F. F., Yamaoka, S., Seto, M. and Nunez, G. Bcl10 and MALT1, independent targets of chromosomal translocation in malt lymphoma, cooperate in a novel NF-kappa B signaling pathway. J. Biol. Chem 2001,276:19012-19019.
    55. Bertin, J., Wang, L., Guo, Y., Jacobson, M. D., Poyet, J. L., Srinivasula, S. M., Merriam, S., DiStefano, P. S. and Alnemri, E. S. CARD11 and CARD14 are novel caspase recruitment domain (CARD)/membraneassociated guanylate kinase (MAGUK) family members that interact with BCL10 and activate NF-kappa B. J. Biol.Chem 2001,276:11877-11882.
    56. Gaide, O., Martinon, F., Micheau, O., Bonnet, D., Thome, M. and Tschopp, J. Carmal, a CARD-containing binding partner of Bel 10, induces Bcl 10 phosphorylation and NF-kappaB activation. FEBS Lett 2001,496:121-127.
    57. McAllister-Lucas, L. M., Inohara, N., Lucas, P. C., Ruland, J., Benito, A., Li, Q., Chen, S., Chen, F. F., Yamaoka, S., Verma, I. M. et al. Bimpl, a MAGUK family member linking protein kinase C activation to Bcl 10-mediated NF-kappaB induction. J. Biol. Chem 2001,276(33):30589-30597.
    58. Wang, L., Guo, Y., Huang, W. J., Ke, X., Poyet, J. L., Manji, G. A., Merriam, S., Glucksmann, M. A., DiStefano, P. S., Alnemri, E. S. et al. Card10 is a novel caspase recruitment domain/membrane-associated guanylate kinase family member that interacts with BCL10 and activates NF-kappa B. J. Biol. Chem 2001,276: 21405-21409.
    59. Dimitratos, S. D., Woods, D. F., Stathakis, D. G. and Bryant, P. J. Signaling pathways are focused at specialized regions of the plasma membrane by scaffolding proteins of the MAGUK family. Bioessays 1999,21:912-921.
    60. Fanning, A. S. and Anderson, J. M. Protein modules as organizers of membrane structure. Curr. Opin. Cell Biol 1999,11:432-439.
    61. Ashkenazi A, Dixit VM. Death receptors:Signaling and modulation. Science 1998, 281:1305-1308.
    62. Zhang J, Cado D, Chen A, Kabra NH, Winoto A. Fas-mediated apoptosis and activation-induced T-cell proliferation are defective in mice lacking FADD/Mortl. Nature 1998,392:296-300.
    63. Nicolas Bide're,1 Andrew L. Snow,1 Keiko Sakai,1Lixin Zheng, and Michael J. Lenardo, Caspase-8 Regulation by Direct Interaction with TRAF6 in T Cell Receptor-Induced NF-kB Activation Current Biology 2006,16:1666-1671
    64. Ye, H., Arron, J.R., Lamothe, B., Cirilli, M., Kobayashi, T.,Shevde, N.K., Segal, D., Dzivenu, O.K., Vologodskaia, M., Yim, M., et al. Distinct molecular mechanism for initiating TRAF6 signalling. Nature 2002,418:443-447.
    65. Chang DW, Xing Z, Capacio VL, Peter ME, Yang X. Interdimer processing mechanism of procaspase-8 activation. EMBO J 2003,22:4132-4142.

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