請用此 Handle URI 來引用此文件:
http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/70989
完整後設資料紀錄
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.advisor | 董馨蓮 | |
dc.contributor.author | Chun-Hsien Wu | en |
dc.contributor.author | 吳俊賢 | zh_TW |
dc.date.accessioned | 2021-06-17T04:47:14Z | - |
dc.date.available | 2023-09-06 | |
dc.date.copyright | 2018-09-06 | |
dc.date.issued | 2018 | |
dc.date.submitted | 2018-08-01 | |
dc.identifier.citation | 1. Zhang, Q., R. Siebert, M. Yan, B. Hinzmann, X. Cui, 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(1): p. 63-68.
2. Akagi, T., M. Motegi, A. Tamura, R. Suzuki, Y. Hosokawa, 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(42): p. 5785-5794. 3. Morgan, J.A., Y. Yin, A.D. Borowsky, F. Kuo, N. Nourmand, 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(24): p. 6205-6213. 4. Lucas, P.C., M. Yonezumi, N. Inohara, L.M. McAllister-Lucas, M.E. Abazeed, et al., 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(22): p. 19012-19019. 5. Uren, A.G., K. O'Rourke, L. Aravind, M.T. Pisabarro, S. Seshagiri, et al., 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(4): p. 961-967. 6. Demeyer, A., J. Staal, and R. Beyaert, Targeting MALT1 proteolytic activity in immunity, inflammation and disease: Good or Bad? Trends Mol. Med., 2016. 22(2): p. 135-150. 7. Jaworski, M. and M. Thome, The paracaspase MALT1: biological function and potential for therapeutic inhibition. Cell. Mol. Life Sci., 2016. 73(3): p. 459-473. 8. Langel, F.D., N.A. Jain, J.S. Rossman, L.M. Kingeter, A.K. Kashyap, et al., Multiple protein domains mediate interaction between Bcl10 and MALT1. J. Biol. Chem., 2008. 283(47): p. 32419-32431. 9. Che, T., Y. You, D. Wang, M.J. Tanner, V.M. Dixit, et al., MALT1/paracaspase is a signaling component downstream of CARMA1 and mediates T cell receptor-induced NF-kappaB activation. J. Biol. Chem., 2004. 279(16): p. 15870-15876. 10. Sun, L., L. Deng, C.K. Ea, Z.P. Xia, and Z.J. Chen, The TRAF6 ubiquitin ligase and TAK1 kinase mediate IKK activation by BCL10 and MALT1 in T lymphocytes. Mol. Cell, 2004. 14(3): p. 289-301. 11. Noels, H., G. van Loo, S. Hagens, V. Broeckx, R. Beyaert, et al., A Novel TRAF6 binding site in MALT1 defines distinct mechanisms of NF-kappaB activation by API2middle dotMALT1 fusions. J. Biol. Chem., 2007. 282(14): p. 10180-10189. 12. Coornaert, B., M. Baens, K. Heyninck, T. Bekaert, M. Haegman, et al., T cell antigen receptor stimulation induces MALT1 paracaspase–mediated cleavage of the NF-κB inhibitor A20. Nat. Immunol., 2008. 9: p. 263. 13. Rebeaud, F., S. Hailfinger, A. Posevitz-Fejfar, M. Tapernoux, R. Moser, et al., The proteolytic activity of the paracaspase MALT1 is key in T cell activation. Nat. Immunol., 2008. 9: p. 272. 14. Meininger, I., R.A. Griesbach, D. Hu, T. Gehring, T. Seeholzer, et al., Alternative splicing of MALT1 controls signalling and activation of CD4(+) T cells. Nat. Commun., 2016. 7: p. 11292. 15. Thome, M., Multifunctional roles for MALT1 in T-cell activation. Nat. Rev. Immunol., 2008. 8(7): p. 495-500. 16. Kane, L.P., J. Lin, and A. Weiss, Signal transduction by the TCR for antigen. Curr. Opin. Immunol., 2000. 12(3): p. 242-249. 17. Matsumoto, R., D. Wang, M. Blonska, H. Li, M. Kobayashi, et al., Phosphorylation of CARMA1 plays a critical role in T cell receptor-mediated NF-κB activation. Immunity, 2005. 23(6): p. 575-585. 18. Sommer, K., B. Guo, J.L. Pomerantz, A.D. Bandaranayake, M.E. Moreno-García, et al., Phosphorylation of the CARMA1 linker controls NF-κB activation. Immunity, 2005. 23(6): p. 561-574. 19. Thome, M., CARMA1, BCL-10 and MALT1 in lymphocyte development and activation. Nat. Rev. Immunol., 2004. 4(5): p. 348-359. 20. Wegener, E. and D. Krappmann, CARD-Bcl10-Malt1 signalosomes: missing link to NF-kappaB. Sci. STKE, 2007. 2007(384): p. pe21. 21. Qiao, Q., C. Yang, C. Zheng, L. Fontan, L. David, et al., Structural architecture of the CARMA1/Bcl10/MALT1 signalosome: nucleation-induced filamentous assembly. Mol. Cell, 2013. 51(6): p. 766-779. 22. Oeckinghaus, A., E. Wegener, V. Welteke, U. Ferch, S.C. Arslan, et al., Malt1 ubiquitination triggers NF-kappaB signaling upon T-cell activation. EMBO J., 2007. 26(22): p. 4634-4645. 23. Wu, C.J. and J.D. Ashwell, NEMO recognition of ubiquitinated Bcl10 is required for T cell receptor-mediated NF-kappaB activation. Proc. Natl. Acad. Sci. U. S. A., 2008. 105(8): p. 3023-3028. 24. Hachmann, J., S.J. Snipas, B.J. van Raam, E.M. Cancino, E.J. Houlihan, et al., Mechanism and specificity of the human paracaspase MALT1. Biochem. J., 2012. 443(1): p. 287-295. 25. Jou, S.Y., C.C. Chang, C.H. Wu, M.R. Chen, C.H. Tsai, et al., BCL10GFP fusion protein as a substrate for analysis of determinants required for mucosa-associated lymphoid tissue 1 (MALT1)-mediated cleavage. J. Biomed. Sci., 2012. 19(1): p. 85. 26. Baens, M., L. Bonsignore, R. Somers, C. Vanderheydt, S.D. Weeks, et al., MALT1 auto-proteolysis is essential for NF-kappaB-dependent gene transcription in activated lymphocytes. PLoS One, 2014. 9(8): p. e103774. 27. Douanne, T., J. Gavard, and N. Bidere, The paracaspase MALT1 cleaves the LUBAC subunit HOIL1 during antigen receptor signaling. J. Cell Sci., 2016. 129(9): p. 1775-1780. 28. Elton, L., I. Carpentier, J. Staal, Y. Driege, M. Haegman, et al., MALT1 cleaves the E3 ubiquitin ligase HOIL-1 in activated T cells, generating a dominant negative inhibitor of LUBAC-induced NF-kappaB signaling. FEBS J., 2016. 283(3): p. 403-412. 29. Ginster, S., M. Bardet, A. Unterreiner, C. Malinverni, F. Renner, et al., Two antagonistic MALT1 auto-cleavage mechanisms reveal a role for TRAF6 to unleash MALT1 activation. PLoS One, 2017. 12(1): p. e0169026. 30. Hailfinger, S., H. Nogai, C. Pelzer, M. Jaworski, K. Cabalzar, et al., Malt1-dependent RelB cleavage promotes canonical NF-κB activation in lymphocytes and lymphoma cell lines. Proc. Natl. Acad. Sci. U. S. A., 2011. 108(35): p. 14596-14601. 31. Jeltsch, K.M., D. Hu, S. Brenner, J. Zöller, G.A. Heinz, et al., Cleavage of roquin and regnase-1 by the paracaspase MALT1 releases their cooperatively repressed targets to promote TH17 differentiation. Nat. Immunol., 2014. 15: p. 1079. 32. Klein, T., S.Y. Fung, F. Renner, M.A. Blank, A. Dufour, et al., The paracaspase MALT1 cleaves HOIL1 reducing linear ubiquitination by LUBAC to dampen lymphocyte NF-kappaB signalling. Nat. Commun., 2015. 6: p. 8777. 33. Staal, J., Y. Driege, T. Bekaert, A. Demeyer, D. Muyllaert, et al., T-cell receptor-induced JNK activation requires proteolytic inactivation of CYLD by MALT1. EMBO J., 2011. 30(9): p. 1742-1752. 34. Uehata, T., H. Iwasaki, A. Vandenbon, K. Matsushita, E. Hernandez-Cuellar, et al., Malt1-induced cleavage of regnase-1 in CD4+ helper T cells regulates immune activation. Cell, 2013. 153(5): p. 1036-1049. 35. Kirisako, T., K. Kamei, S. Murata, M. Kato, H. Fukumoto, et al., A ubiquitin ligase complex assembles linear polyubiquitin chains. EMBO J., 2006. 25(20): p. 4877-4887. 36. Sato, Y., H. Fujita, A. Yoshikawa, M. Yamashita, A. Yamagata, et al., Specific recognition of linear ubiquitin chains by the Npl4 zinc finger (NZF) domain of the HOIL-1L subunit of the linear ubiquitin chain assembly complex. Proc. Natl. Acad. Sci. U. S. A., 2011. 108(51): p. 20520-20525. 37. Rahighi, S., F. Ikeda, M. Kawasaki, M. Akutsu, N. Suzuki, et al., Specific recognition of linear ubiquitin chains by NEMO is important for NF-κB activation. Cell, 2009. 136(6): p. 1098-1109. 38. Fujita, H., S. Rahighi, M. Akita, R. Kato, Y. Sasaki, et al., Mechanism underlying IkappaB kinase activation mediated by the linear ubiquitin chain assembly complex. Mol. Cell. Biol., 2014. 34(7): p. 1322-1335. 39. Siegel, R., D. Naishadham, and A. Jemal, Cancer statistics, 2013. CA Cancer J. Clin., 2013. 63(1): p. 11-30. 40. Alizadeh, A.A., M.B. Eisen, R.E. Davis, C. Ma, I.S. Lossos, et al., Distinct types of diffuse large B-cell lymphoma identified by gene expression profiling. Nature, 2000. 403(6769): p. 503-511. 41. Lenz, G., G.W. Wright, N.C. Emre, H. Kohlhammer, S.S. Dave, et al., Molecular subtypes of diffuse large B-cell lymphoma arise by distinct genetic pathways. Proc. Natl. Acad. Sci. U. S. A., 2008. 105(36): p. 13520-13525. 42. Wright, G., B. Tan, A. Rosenwald, E.H. Hurt, A. Wiestner, et al., A gene expression-based method to diagnose clinically distinct subgroups of diffuse large B cell lymphoma. Proc. Natl. Acad. Sci. U. S. A., 2003. 100(17): p. 9991-9996. 43. Lenz, G., G. Wright, S.S. Dave, W. Xiao, J. Powell, et al., Stromal gene signatures in large-B-cell lymphomas. N. Engl. J. Med., 2008. 359(22): p. 2313-2323. 44. Davis, R.E., K.D. Brown, U. Siebenlist, and L.M. Staudt, Constitutive nuclear factor κB activity is required for survival of activated B cell–like diffuse large B cell lymphoma cells. J. Exp. Med., 2001. 194(12): p. 1861-1874. 45. Roschewski, M., L.M. Staudt, and W.H. Wilson, Diffuse large B-cell lymphoma-treatment approaches in the molecular era. Nat. Rev. Clin. Oncol., 2014. 11(1): p. 12-23. 46. Davis, R.E., V.N. Ngo, G. Lenz, P. Tolar, R. Young, et al., Chronic active B cell receptor signaling in diffuse large B cell lymphoma. Nature, 2010. 463(7277): p. 88-92. 47. Nagel, D., M. Bognar, A.C. Eitelhuber, K. Kutzner, M. Vincendeau, et al., Combinatorial BTK and MALT1 inhibition augments killing of CD79 mutant diffuse large B cell lymphoma. Oncotarget, 2015. 6(39): p. 42232-42242. 48. Lenz, G., R.E. Davis, V.N. Ngo, L. Lam, T.C. George, et al., Oncogenic CARD11 mutations in human diffuse large B cell lymphoma. Science, 2008. 319(5870): p. 1676-1679. 49. Kato, M., M. Sanada, I. Kato, Y. Sato, J. Takita, et al., Frequent inactivation of A20 in B-cell lymphomas. Nature, 2009. 459: p. 712. 50. Ngo, V.N., R.M. Young, R. Schmitz, S. Jhavar, W. Xiao, et al., Oncogenically active MYD88 mutations in human lymphoma. Nature, 2011. 470(7332): p. 115-119. 51. Ferch, U., B. Kloo, A. Gewies, V. Pfänder, M. Düwel, et al., Inhibition of MALT1 protease activity is selectively toxic for activated B cell–like diffuse large B cell lymphoma cells. J. Exp. Med., 2009. 206(11): p. 2313-2320. 52. Hailfinger, S., G. Lenz, V. Ngo, A. Posvitz-Fejfar, F. Rebeaud, et al., Essential role of MALT1 protease activity in activated B cell-like diffuse large B-cell lymphoma. Proc. Natl. Acad. Sci. U. S. A., 2009. 106(47): p. 19946-19951. 53. Nagel, D., S. Spranger, M. Vincendeau, M. Grau, S. Raffegerst, et al., Pharmacologic inhibition of MALT1 protease by phenothiazines as a therapeutic approach for the treatment of aggressive ABC-DLBCL. Cancer Cell, 2012. 22(6): p. 825-837. 54. Fontan, L., C. Yang, V. Kabaleeswaran, L. Volpon, M.J. Osborne, et al., MALT1 small molecule inhibitors specifically suppress ABC-DLBCL in vitro and in vivo. Cancer Cell, 2012. 22(6): p. 812-824. 55. Guiet, C. and P. Vito, Caspase recruitment domain (Card-Dependent) cytoplasmic filaments mediate Bcl10-induced Nf-κb activation. J. Cell Biol., 2000. 148(6): p. 1131-1140. 56. Ngo, V.N., R.E. Davis, L. Lamy, X. Yu, H. Zhao, et al., A loss-of-function RNA interference screen for molecular targets in cancer. Nature, 2006. 441: p. 106. 57. Gewies, A., O. Gorka, H. Bergmann, K. Pechloff, F. Petermann, et al., Uncoupling Malt1 threshold function from paracaspase activity results in destructive autoimmune inflammation. Cell Rep, 2014. 9(4): p. 1292-1305. 58. Bornancin, F., F. Renner, R. Touil, H. Sic, Y. Kolb, et al., Deficiency of MALT1 paracaspase activity results in unbalanced regulatory and effector T and B cell responses leading to multiorgan inflammation. J. Immunol., 2015. 194(8): p. 3723-3734. 59. Yu, J.W., S. Hoffman, A.M. Beal, A. Dykon, M.A. Ringenberg, et al., MALT1 protease activity is required for innate and adaptive immune responses. PLoS One, 2015. 10(5): p. e0127083. 60. Jaworski, M., B.J. Marsland, J. Gehrig, W. Held, S. Favre, et al., Malt1 protease inactivation efficiently dampens immune responses but causes spontaneous autoimmunity. EMBO J., 2014. 33(23): p. 2765-2781. | |
dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/70989 | - |
dc.description.abstract | Paracaspase mucosa-associated lymphoid tissue lymphoma translocation 1 (MALT1)能透過其鷹架蛋白功能來調控數種由不同接受器所引起的NF-κB訊息傳遞路徑。MALT1的蛋白水解活性被認為可以對數種NF-κB負向調控因子進行切割使其去活性,進而強化NF-κB活性。本研究發現,MALT1與具有聚合作用能力的BCL10共同表現時會引發本身的自我切割。MALT1自我切割的位點是在C端的Arg-781。在試管中切割試驗可以證實MALT1的自我切割能力;使用TPA/ionomycin或anti-CD3抗體刺激淋巴細胞,可偵測到微量的MALT1自我切割。然而在活化性瀰漫性大B細胞淋巴瘤細胞OCI-Ly3及HBL-1上可以觀察到明顯的MALT1於Arg-781的自我切割。自我切割後的MALT1與TRAF6結合的能力會降低,進而會使其引起NF-κB活化的能力下降。在內生性MALT1被knockdown的Jurkat細胞(Jurkat-S-MD)中表現野生型的MALT1、去蛋白水解活性的MALT1_C464A、自我切割能力缺乏的MALT1_R781L或C端被截短的MALT1_1-781,並以TPA/ionomycin激刺後,缺乏自我切割能力的MALT1_R781L保有蛋白水解活性並能夠誘發與MALT1相同的初始IκBα磷酸化活性。C端被截短的MALT1誘發較弱的初始IκBα磷酸化,並且使IL-2與IFN-γ的表現量下降。MALT1的蛋白水解活性對活化型瀰漫性大B細胞淋巴瘤細胞的生長及存活是必需的,在HBL-1細胞中誘發表現去蛋白水解活性的MAL1_C464A或缺乏自我切割能力的MALT1_R781L,會使細胞生長受到抑制。此一結果顯示MALT1於Arg-781的自我切割參與並調控活化型瀰漫性大B細胞淋巴瘤細胞的生長。 | zh_TW |
dc.description.abstract | Paracaspase mucosa-associated lymphoid tissue lymphoma translocation 1 (MALT1) can regulate several NF-κB signaling pathways caused by different receptors through its scaffold protein function. MALT1 protease activity is shown to inactivate several negative regulators of NF-κB signaling and augment NF-κB activation ability. In this study, MALT1 was demonstrated to autoprocess itself in the presence of oligomerization-competent BCL10. Cleavage occurred after Arg-781 located in the C-terminus of MALT1. The autocleavage of MALT1 could be observed in in-vitro cleavage assay. Cleavage at Arg-781 was detectable but marginal after activation with TPA/ionomycin or anti-CD3 antibody in lymphocytes. However, cleavage at Arg-781 was evident in ABC-DLBCL cells such as OCI-Ly3, HBL-1. Shortened MALT1 cleavage products showed attenuated binding ability with TRAF6. Its NF-κB activation ability was also weakened. Various MALT1 constructs including wild type, catalytically-inactive (MALT1_C464A), cleavage-defective (MALT1_R781L), or truncated (MALT1_1-781) form of MALT1 was introduced into MALT1-knocked-down-Jurkat T cells. Cleavage-defective MALT1_R781L retained its proteolytic and initial IκBα phosphorylation activity as MALT1. Truncated MALT1_1-781 mutant showed weakness in IBα phosphorylation and the expression of NF-κB targets IL-2 and IFN-γ. The proteolytic activity of MALT1 is essential for the survival of ABC-DLBCL cells. HBL-1 cells with induced expression of catalytically-inactive MALT1_C464A or cleavage-defective MALT1_R781L exhibited characteristic of retarded-growth. These findings suggested that cleavage at Arg-781 of MALT1 played a role in the survival of ABC-DLBCL cells. | en |
dc.description.provenance | Made available in DSpace on 2021-06-17T04:47:14Z (GMT). No. of bitstreams: 1 ntu-107-D97445004-1.pdf: 4612101 bytes, checksum: 61061e3754014ddaa168d409f2198856 (MD5) Previous issue date: 2018 | en |
dc.description.tableofcontents | 目錄
口試委員會審定書 i 摘要 ii Abstract iii 目錄 iv 圖目錄 vii 表目錄 x 第一章、 序論 1 1.1 MALT1 1 1.2 MALT1會參與NF-κB訊息傳遞路徑,扮演鷹架蛋白的角色 2 1.3 MALT1的蛋白水解活性(proteolytic activity)在NF-κB的訊息傳遞路徑上扮演重要的角色 3 1.4 MALT1需先進行聚合作用(oligomerization)才能具有NF-κB活化能力 3 1.5 瀰漫性大B細胞淋巴瘤(Diffuse Large B cell Lymphoma, DLBCL) 6 1.6 MALT1的蛋白水解活性對活化型瀰漫性大B細胞淋巴瘤的生長是重要的 7 第二章、 研究目的 9 第三章、 材料與方法 10 3.1 質體與抗體 10 3.2 細胞培養 13 3.3 冷凍細胞 14 3.4 刺激細胞活化的藥物與MALT1抑制劑 15 3.5 細菌轉型 15 3.6 小量質體製備 15 3.7 大量質體製備 16 3.8 細胞轉染 17 3.9 製備慢病毒載體顆粒 17 3.10 建立穩定表現sh-MALT1之突變細胞株及MALT1 拯救(rescue)細胞株 18 3.11 以TPA (12-o-tetradecanoylphorbol-13-acetate)/ionomycin誘導NF-κB活化 18 3.12 萃取核醣核酸 18 3.13 即時聚合酶鏈反應 19 3.14 萃取細胞中的蛋白質 19 3.15 蛋白質濃度測定 19 3.16 十二烷基硫酸鈉聚丙烯醯胺凝膠電泳 19 3.17 西方墨點法分析 20 3.18 免疫沉澱與去磷酸酵素作用 21 3.19 冷光酵素測定 21 3.20 電穿孔方法 21 3.21 試管內MALT1切割試驗 22 3.22 酵素連結免疫分析法 22 3.23 細胞生長率試驗 22 第四章、 結果 23 4.1 BCL10活化MALT1並且誘發MALT1的自我切割 23 4.2 MALT1於試管內進行自我切割 24 4.3 在活化的T和B淋巴細胞中,MALT1發生自我切割 24 4.4 MALT1在Arg-781自我切割,減弱其NF-κB活化的能力 26 4.5 C端被截短的MALT1在活化的Jurkat細胞中表現出較弱的NF-κB活化能力 27 4.6 MALT1在Arg-781的自我切割對於活化型瀰漫性大細胞淋巴瘤細胞的存活是需要的 28 第五章、 討論 30 第六章、 結果圖表 35 第七章、 附錄圖表 57 第八章、 參考文獻 79 圖目錄 圖一、 於HEK293T中轉染BCL10與MALT1,可以誘發MALT1的自我切割 35 圖二、 MALT1的蛋白水解活性對於本身的自我切割是必需的 36 圖三、 MALT1的自我切割是位於其C端 37 圖四、 Arg-781為MALT1的自我切割位點 38 圖五、 MALT1於試管中進行自我切割 39 圖六、 在活化的T細胞中,MALT1進行自我切割 40 圖七、 在活化的T細胞中,MALT1進行自我切割 41 圖八、 在活化的小鼠脾臟細胞中,MALT1進行自我切割 42 圖九、 在活化的BJAB細胞中,MALT1進行自我切割 43 圖十、 在活化的EBV+-Akata細胞中,MALT1不會進行自我切割 44 圖十一、 在活化型瀰漫性大B細胞淋巴瘤細胞中,MALT1進行自我切割 45 圖十二、 在活化型瀰漫性大B細胞淋巴瘤細胞 OCI-Ly3中的 MALT1自我切割可被MI-2抑制 46 圖十三、 C端被截短的MALT1具較弱與TRAF6進行結合的能力 47 圖十四、 C端被截短的MALT1具有較弱的NF-κB活化能力 48 圖十五、 C端被截短的GB-MALT1_1-781具有較弱的NF-κB活化能力 49 圖十六、 使用不同的干擾核醣核酸降低內生性 MALT1表現與在內生性 MALT1 knockdown的 Jurkat細胞(Jurkat-S-MD)表現 MALT1拯救質體 50 圖十七、 MALT1 Arg-781的自我切割減弱在 Jurkat細胞中誘發 NF-κB活化的能力 51 圖十八、 於 MALT1 Arg-781的自我切割減弱在 Jurkat細胞中誘發 NF-κB活化的能力 52 圖十九、 於MALT1 Arg-781的自我切割降低NF-κB活化後IL-2與IFN-γ的表現量 53 圖二十、 在HBL-1細胞中表現不同特性的MALT1與MALT1B 54 圖二十一、 自我切割位點突變的 MALT1_R781L以及去蛋白水解活性的MALT1_C464A會影響 HBL-1細胞的生長 55 圖二十二、 MALT1的蛋白水解活性調控活化型瀰漫性大B細胞淋巴瘤細胞生長假說圖 56 附圖一、 MALT1結構圖 57 附圖二、 CBM複合體在NF-κB訊息傳遞路徑上所扮演的角色 58 附圖三、 NF-κB訊息傳遞路徑 59 附圖四、 活化型瀰漫性大B細胞淋巴瘤細胞NF-κB訊息傳遞路徑持續活化機制 60 附圖五、 pRc/CMV MALT1_R781L、pRc/CMV MALT1_1-781與pRc/CMV MALT1_R723L, K724L的質體構築流程圖,以pRc/CMV MALT1_R781L為例 61 附圖六、 pRc/CMV MALT1-FLAG的質體構築流程圖 62 附圖七、 pCMV6/XL5 GB-MALT1_R781L與pCMV6/XL5 GB-MALT1_1-781的質體構築流程圖,以pCMV6/XL5 GB-MALT1_R781L為例 63 附圖八、 pRc/CMV MALT1_R、pRc/CMV MALT1_R781L_R與pRc/CMV MALT1_1-781_R的質體構築流程圖,以pRc/CMV MALT1_R為例64 附圖九、 pCMV6/XL5 MALT1_C464A_R的質體構築圖 65 附圖十、 pLAS3w.Pneo MALT1_R、pLAS3w.Pneo MALT1_R781L_R、pLAS3w.Pneo MALT1_1-781_R的質體構築流程圖,以pLAS3w.Pneo MALT1_R為例 66 附圖十一、 pLAS3w.Pneo MALT1_C464A_R的質體構築流程圖 67 附圖十二、 pRc/CMV MALT1B_R、pRc/CMV MALT1B_R770L_R與pRc/CMV MALT1B_1-770_R的質體構築流程圖,以pRc/CMV MALT1B_R例 68 附圖十三、 pAS4.1w.Ppuro-aOn MALT1_R、pAS4.1w.Ppuro-aOn MALT1_R781L_R、pAS4.1w.Ppuro-aOn MALT1_1-781_R、pAS4.1w.Ppuro-aOn MALT1B_R、pAS4.1w.Ppuro-aOn MALT1B_R770L_R與pAS4.1w.Ppuro-aOn MALT1B_1-770_R的質體構築流程圖,以pAS4.1w.Ppuro-aOn MALT1_R為例 69 附圖十四、 pAS4.1w.Ppuro-aOn MALT1_C464A_R的質體構築流程圖 70 附圖十五、 本研究所用之MALT1質體卡通示意圖 71 附圖十六、 BCL10 蛋白質純化的純度 72 附圖十七、 His-tag MALT1 蛋白質純化的純度 73 附圖十八、 於螢光顯微鏡下觀察BCL10GFP和BCL10_L41RGFP 74 表目錄 附表一、 實驗中所用之質體列表 75 附表二、 實驗中所使用之抗體列表 78 | |
dc.language.iso | zh-TW | |
dc.title | Paracaspase MALT1於Arg-781的自我切割減弱
NF-κB訊號並調控活化型瀰漫性大B細胞淋巴瘤細胞生長 | zh_TW |
dc.title | Autocleavage of the paracaspase MALT1 at Arg-781 attenuates NF-κB signaling and regulates the growth of activated B-cell like diffuse large B-cell lymphoma cells | en |
dc.type | Thesis | |
dc.date.schoolyear | 106-2 | |
dc.description.degree | 博士 | |
dc.contributor.oralexamcommittee | 鄧述諄,陳美如,徐立中,莊雙恩 | |
dc.subject.keyword | MALT1,自我切割,NF-κB,蛋白水解活性,活化型瀰漫性大B細胞瘤淋巴瘤, | zh_TW |
dc.subject.keyword | MALT1,autocleavage,NF-κB,proteolytic activity,ABC-DLBCL, | en |
dc.relation.page | 86 | |
dc.identifier.doi | 10.6342/NTU201802063 | |
dc.rights.note | 有償授權 | |
dc.date.accepted | 2018-08-01 | |
dc.contributor.author-college | 醫學院 | zh_TW |
dc.contributor.author-dept | 微生物學研究所 | zh_TW |
顯示於系所單位: | 微生物學科所 |
文件中的檔案:
檔案 | 大小 | 格式 | |
---|---|---|---|
ntu-107-1.pdf 目前未授權公開取用 | 4.5 MB | Adobe PDF |
系統中的文件,除了特別指名其著作權條款之外,均受到著作權保護,並且保留所有的權利。