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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 董馨蓮(Shin-Lian Doong) | |
| dc.contributor.author | Su-Hsin Tsang | en |
| dc.contributor.author | 臧素心 | zh_TW |
| dc.date.accessioned | 2021-05-20T20:09:22Z | - |
| dc.date.available | 2019-07-27 | |
| dc.date.available | 2021-05-20T20:09:22Z | - |
| dc.date.copyright | 2009-09-15 | |
| dc.date.issued | 2009 | |
| dc.date.submitted | 2009-07-30 | |
| dc.identifier.citation | 1. 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., Pan, L., Crook, T., Hamoudi, R., Isaacson, P.G., Dyer, M.J. (1999) BCL10 is involved in t(1;14)(p22;q32) of MALT B cell lymphoma and mutated in multiple tumor types. Cell 96, 35-45.
2. Zhang, Q., Siebert, R., Yan, M., Hinzmann, B., Cui, X., Xue, L., Rakestraw, K.M., Naeve, C.W., Beckmann, G., Weisenburger, D.D., Sanger, W.G., Nowotny, H., Vesely, M., Callet-Bauchu, E., Salles, G., Dixit, V.M., Rosenthal, A., Schlegelberger, B., Morris, S.W. (1999) Inactivating mutations and overexpression of BCL10, a caspase recruitment domain-containing gene, in MALT lymphoma with t(1;14)(p22;q32). Nat Genet 22, 63-8. 3. Koseki, T., Inohara, N., Chen, S., Carrio, R., Merino, J., Hottiger, M.O., Nabel, G.J., Nunez, G. (1999) CIPER, a novel NF-κB-activating protein containing a caspase recruitment domain with homology to Herpesvirus-2 protein E10. J Biol Chem 274, 9955-61. 4. Srinivasula, S.M., Ahmad, M., Lin, J.H., Poyet, J.L., Fernandes-Alnemri, T., Tsichlis, P.N., Alnemri, E.S. (1999) CLAP, a novel caspase recruitment domain-containing protein in the tumor necrosis factor receptor pathway, regulates NF-κB activation and apoptosis. J Biol Chem 274, 17946-54. 5. Yan, M., Lee, J., Schilbach, S., Goddard, A., Dixit, V. (1999) mE10, a novel caspase recruitment domain-containing proapoptotic molecule. J Biol Chem 274, 10287-92. 6. Thome, M., Martinon, F., Hofmann, K., Rubio, V., Steiner, V., Schneider, P., Mattmann, C., Tschopp, J. (1999) Equine herpesvirus-2 E10 gene product, but not its cellular homologue, activates NF-κB transcription factor and c-Jun N-terminal kinase. J Biol Chem 274, 9962-8. 7. Lucas, P.C., Yonezumi, M., Inohara, N., McAllister-Lucas, L.M., Abazeed, M.E., Chen, F.F., Yamaoka, S., Seto, M., Nunez, G. (2001) BCL10 and MALT1, independent targets of chromosomal translocation in malt lymphoma, cooperate in a novel NF-κ B signaling pathway. J Biol Chem 276, 19012-9. 8. Wegener, E., Oeckinghaus, A., Papadopoulou, N., Lavitas, L., Schmidt-Supprian, M., Ferch, U., Mak, T.W., Ruland, J., Heissmeyer, V., Krappmann, D. (2006) Essential role for IκB kinase beta in remodeling CARMA1-BCL10-MALT1 complexes upon T cell activation. Mol Cell 23, 13-23. 9. Gaide, O., Martinon, F., Micheau, O., Bonnet, D., Thome, M., Tschopp, J. (2001) CARMA1, a CARD-containing binding partner of BCL10, induces BCL10 phosphorylation and NF-κB activation. FEBS Lett 496, 121-7. 10. Ishiguro, K., Ando, T., Goto, H., Xavier, R. (2007) BCL10 is phosphorylated on Ser138 by Ca2+/calmodulin-dependent protein kinase II. Mol Immunol 44, 2095-100. 11. Lobry, C., Lopez, T., Israel, A., Weil, R. (2007) Negative feedback loop in T cell activation through IκB kinase-induced phosphorylation and degradation of BCL10. Proc Natl Acad Sci U S A 104, 908-13. 12. Scharschmidt, E., Wegener, E., Heissmeyer, V., Rao, A., Krappmann, D. (2004) Degradation of BCL10 induced by T-cell activation negatively regulates NF-κ B signaling. Mol Cell Biol 24, 3860-73. 13. Ruefli-Brasse, A.A., Lee, W.P., Hurst, S., Dixit, V.M. (2004) Rip2 participates in BCL10 signaling and T-cell receptor-mediated NF-κB activation. J Biol Chem 279, 1570-4. 14. Rebeaud, F., Hailfinger, S., Posevitz-Fejfar, A., Tapernoux, M., Moser, R., Rueda, D., Gaide, O., Guzzardi, M., Iancu, E.M., Rufer, N., Fasel, N., Thome, M. (2008) The proteolytic activity of the paracaspase MALT1 is key in T cell activation. Nat Immunol 9, 272-81. 15. 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., Marynen, P. (1999) The apoptosis inhibitor gene API2 and a novel 18q gene, MLT, are recurrently rearranged in the t(11;18)(q21;q21) associated with mucosa-associated lymphoid tissue lymphomas. Blood 93, 3601-9. 16. Akagi, T., Motegi, M., Tamura, A., Suzuki, R., Hosokawa, Y., Suzuki, H., Ota, H., Nakamura, S., Morishima, Y., Taniwaki, M., Seto, M. (1999) 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 18, 5785-94. 17. 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., Harris, N.L., Weisenburger, D., Pinkus, G.S., Fletcher, J.A., Sklar, J. (1999) 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 59, 6205-13. 18. Uren, A.G., O'Rourke, K., Aravind, L.A., Pisabarro, M.T., Seshagiri, S., Koonin, E.V., Dixit, V.M. (2000) Identification of paracaspases and metacaspases: two ancient families of caspase-like proteins, one of which plays a key role in MALT lymphoma. Mol Cell 6, 961-7. 19. Zhou, H., Du, M.Q., Dixit, V.M. (2005) Constitutive NF-κB activation by the t(11;18)(q21;q21) product in MALT lymphoma is linked to deregulated ubiquitin ligase activity. Cancer Cell 7, 425-31. 20. Noels, H., van Loo, G., Hagens, S., Broeckx, V., Beyaert, R., Marynen, P., Baens, M. (2007) A Novel TRAF6 binding site in MALT1 defines distinct mechanisms of NF-κB activation by API2middle dotMALT1 fusions. J Biol Chem 282, 10180-9. 21. Coornaert, B., Baens, M., Heyninck, K., Bekaert, T., Haegman, M., Staal, J., Sun, L., Chen, Z.J., Marynen, P., Beyaert, R. (2008) T cell antigen receptor stimulation induces MALT1 paracaspase-mediated cleavage of the NF-κB inhibitor A20. Nat Immunol 9, 263-71. 22. Sun, L., Deng, L., Ea, C.K., Xia, Z.P., Chen, Z.J. (2004) The TRAF6 ubiquitin ligase and TAK1 kinase mediate IKK activation by BCL10 and MALT1 in T lymphocytes. Mol Cell 14, 289-301. 23. Ruefli-Brasse, A.A., French, D.M., Dixit, V.M. (2003) Regulation of NF-κB-dependent lymphocyte activation and development by paracaspase. Science 302, 1581-4. 24. Heyninck, K., Beyaert, R. (2005) A20 inhibits NF-κB activation by dual ubiquitin-editing functions. Trends Biochem Sci 30, 1-4. 25. Kinashi, T. (2005) Intracellular signalling controlling integrin activation in lymphocytes. Nat Rev Immunol 5, 546-59. 26. Bertin, J., Guo, Y., Wang, L., Srinivasula, S.M., Jacobson, M.D., Poyet, J.L., Merriam, S., Du, M.Q., Dyer, M.J., Robison, K.E., DiStefano, P.S., Alnemri, E.S. (2000) CARD9 is a novel caspase recruitment domain-containing protein that interacts with BCL10/CLAP and activates NF-κ B. J Biol Chem 275, 41082-6. 27. Bertin, J., Wang, L., Guo, Y., Jacobson, M.D., Poyet, J.L., Srinivasula, S.M., Merriam, S., DiStefano, P.S., Alnemri, E.S. (2001) CARD11 and CARD14 are novel caspase recruitment domain (CARD)/membrane-associated guanylate kinase (MAGUK) family members that interact with BCL10 and activate NF-κB. J Biol Chem 276, 11877-82. 28. 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., Bertin, J. (2001) CARD10 is a novel caspase recruitment domain/membrane-associated guanylate kinase family member that interacts with BCL10 and activates NF-κB. J Biol Chem 276, 21405-9. 29. Lupas, A. (1996) Coiled coils: new structures and new functions. Trends Biochem Sci 21, 375-82. 30. Fanning, A.S., Anderson, J.M. (1999) Protein modules as organizers of membrane structure. Curr Opin Cell Biol 11, 432-9. 31. Wegener, E., Krappmann, D. (2007) CARD-BCL10-MALT1 signalosomes: missing link to NF-κB. Sci STKE 2007, pe21. 32. Clements, J.L., Boerth, N.J., Lee, J.R., Koretzky, G.A. (1999) Integration of T cell receptor-dependent signaling pathways by adapter proteins. Annu Rev Immunol 17, 89-108. 33. Schulze-Luehrmann, J., Ghosh, S. (2006) Antigen-receptor signaling to nuclear factor κ B. Immunity 25, 701-15. 34. Karin, M., Lin, A. (2002) NF-κB at the crossroads of life and death. Nat Immunol 3, 221-7. 35. Karin, M., Ben-Neriah, Y. (2000) Phosphorylation meets ubiquitination: the control of NF-[κ]B activity. Annu Rev Immunol 18, 621-63. 36. Deng, L., Wang, C., Spencer, E., Yang, L., Braun, A., You, J., Slaughter, C., Pickart, C., Chen, Z.J. (2000) Activation of the IκB kinase complex by TRAF6 requires a dimeric ubiquitin-conjugating enzyme complex and a unique polyubiquitin chain. Cell 103, 351-61. 37. Wang, C., Deng, L., Hong, M., Akkaraju, G.R., Inoue, J., Chen, Z.J. (2001) TAK1 is a ubiquitin-dependent kinase of MKK and IKK. Nature 412, 346-51. 38. Gaide, O., Favier, B., Legler, D.F., Bonnet, D., Brissoni, B., Valitutti, S., Bron, C., Tschopp, J., Thome, M. (2002) CARMA1 is a critical lipid raft-associated regulator of TCR-induced NF-κ B activation. Nat Immunol 3, 836-43. 39. Pomerantz, J.L., Denny, E.M., Baltimore, D. (2002) CARD11 mediates factor-specific activation of NF-κB by the T cell receptor complex. EMBO J 21, 5184-94. 40. Egawa, T., Albrecht, B., Favier, B., Sunshine, M.J., Mirchandani, K., O'Brien, W., Thome, M., Littman, D.R. (2003) Requirement for CARMA1 in antigen receptor-induced NF-κ B activation and lymphocyte proliferation. Curr Biol 13, 1252-8. 41. Newton, K., Dixit, V.M. (2003) Mice lacking the CARD of CARMA1 exhibit defective B lymphocyte development and impaired proliferation of their B and T lymphocytes. Curr Biol 13, 1247-51. 42. Hara, H., Wada, T., Bakal, C., Kozieradzki, I., Suzuki, S., Suzuki, N., Nghiem, M., Griffiths, E.K., Krawczyk, C., Bauer, B., D'Acquisto, F., Ghosh, S., Yeh, W.C., Baier, G., Rottapel, R., Penninger, J.M. (2003) The MAGUK family protein CARD11 is essential for lymphocyte activation. Immunity 18, 763-75. 43. 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., Mak, T.W. (2001) BCL10 is a positive regulator of antigen receptor-induced activation of NF-κB and neural tube closure. Cell 104, 33-42. 44. Ruland, J., Duncan, G.S., Wakeham, A., Mak, T.W. (2003) Differential requirement for MALT1 in T and B cell antigen receptor signaling. Immunity 19, 749-58. 45. Che, T., You, Y., Wang, D., Tanner, M.J., Dixit, V.M., Lin, X. (2004) MALT1/paracaspase is a signaling component downstream of CARMA1 and mediates T cell receptor-induced NF-κB activation. J Biol Chem 279, 15870-6. 46. Oeckinghaus, A., Wegener, E., Welteke, V., Ferch, U., Arslan, S.C., Ruland, J., Scheidereit, C., Krappmann, D. (2007) MALT1 ubiquitination triggers NF-κB signaling upon T-cell activation. EMBO J 26, 4634-45. 47. Thome, M. (2004) CARMA1, BCL-10 and MALT1 in lymphocyte development and activation. Nat Rev Immunol 4, 348-59. 48. Gross, O., Grupp, C., Steinberg, C., Zimmermann, S., Strasser, D., Hannesschlager, N., Reindl, W., Jonsson, H., Huo, H.R., Littman, D.R., Peschel, C., Yokoyama, W.M., Krug, A., Ruland, J. (2008) Multiple ITAM-coupled NK-cell receptors engage the BCL10/MALT1 complex via CARMA1 for NF-κB and MAPK activation to selectively control cytokine production. Blood 112, 2421-2428. 49. Hara, H., Ishihara, C., Takeuchi, A., Xue, L.Q., Morris, S.W., Penninger, J.M., Yoshida, H., Saito, T. (2008) Cell type-specific regulation of ITAM-mediated NF-κ B activation by the adaptors, CARMA1 and CARD9. J Immunol 181, 918-930. 50. Malarkannan, S., Regunathan, J., Chu, H., Kutlesa, S., Chen, Y., Zeng, H., Wen, R., Wang, D. (2007) BCL10 plays a divergent role in NK cell-mediated cytotoxicity and cytokine generation. J Immunol 179, 3752-62. 51. Hara, H., Ishihara, C., Takeuchi, A., Imanishi, T., Xue, L., Morris, S.W., Inui, M., Takai, T., Shibuya, A., Saijo, S., Iwakura, Y., Ohno, N., Koseki, H., Yoshida, H., Penninger, J.M., Saito, T. (2007) The adaptor protein CARD9 is essential for the activation of myeloid cells through ITAM-associated and Toll-like receptors. Nat Immunol 8, 619-29. 52. Gross, O., Gewies, A., Finger, K., Schafer, M., Sparwasser, T., Peschel, C., Forster, I., Ruland, J. (2006) CARD9 controls a non-TLR signalling pathway for innate anti-fungal immunity. Nature 442, 651-6. 53. Klemm, S., Gutermuth, J., Hultner, L., Sparwasser, T., Behrendt, H., Peschel, C., Mak, T.W., Jakob, T., Ruland, J. (2006) The BCL10-MALT1 complex segregates Fc epsilon RI-mediated nuclear factor κ B activation and cytokine production from mast cell degranulation. J Exp Med 203, 337-47. 54. Chen, Y., Pappu, B.P., Zeng, H., Xue, L., Morris, S.W., Lin, X., Wen, R., Wang, D. (2007) B cell lymphoma 10 is essential for FcepsilonR-mediated degranulation and IL-6 production in mast cells. J Immunol 178, 49-57. 55. Grabiner, B.C., Blonska, M., Lin, P.C., You, Y., Wang, D., Sun, J., Darnay, B.G., Dong, C., Lin, X. (2007) CARMA3 deficiency abrogates G protein-coupled receptor-induced NF-{κ}B activation. Genes Dev 21, 984-96. 56. Wang, D., You, Y., Lin, P.C., Xue, L., Morris, S.W., Zeng, H., Wen, R., Lin, X. (2007) BCL10 plays a critical role in NF-κB activation induced by G protein-coupled receptors. Proc Natl Acad Sci U S A 104, 145-50. 57. McAllister-Lucas, L.M., Ruland, J., Siu, K., Jin, X., Gu, S., Kim, D.S., Kuffa, P., Kohrt, D., Mak, T.W., Nunez, G., Lucas, P.C. (2007) CARMA3/BCL10/MALT1-dependent NF-κB activation mediates angiotensin II-responsive inflammatory signaling in nonimmune cells. Proc Natl Acad Sci U S A 104, 139-44. 58. Klemm, S., Zimmermann, S., Peschel, C., Mak, T.W., Ruland, J. (2007) BCL10 and MALT1 control lysophosphatidic acid-induced NF-κB activation and cytokine production. Proc Natl Acad Sci U S A 104, 134-8. 59. Bhattacharyya, S., Borthakur, A., Pant, N., Dudeja, P.K., Tobacman, J.K. (2007) BCL10 mediates LPS-induced activation of NF-κB and IL-8 in human intestinal epithelial cells. Am J Physiol Gastrointest Liver Physiol 293, G429-37. 60. Dong, W., Liu, Y., Peng, J., Chen, L., Zou, T., Xiao, H., Liu, Z., Li, W., Bu, Y., Qi, Y. (2006) The IRAK-1-BCL10-MALT1-TRAF6-TAK1 cascade mediates signaling to NF-κB from Toll-like receptor 4. J Biol Chem 281, 26029-40. 61. Liu, Y., Dong, W., Chen, L., Xiang, R., Xiao, H., De, G., Wang, Z., Qi, Y. (2004) BCL10 mediates lipopolysaccharide/toll-like receptor-4 signaling through interaction with Pellino2. J Biol Chem 279, 37436-44. 62. Wright, S.D., Ramos, R.A., Tobias, P.S., Ulevitch, R.J., Mathison, J.C. (1990) CD14, a receptor for complexes of lipopolysaccharide (LPS) and LPS binding protein. Science 249, 1431-3. 63. Brown, G.D., Gordon, S. (2001) Immune recognition. A new receptor for beta-glucans. Nature 413, 36-7. 64. Rogers, N.C., Slack, E.C., Edwards, A.D., Nolte, M.A., Schulz, O., Schweighoffer, E., Williams, D.L., Gordon, S., Tybulewicz, V.L., Brown, G.D., Reis e Sousa, C. (2005) Syk-dependent cytokine induction by Dectin-1 reveals a novel pattern recognition pathway for C type lectins. Immunity 22, 507-17. 65. Brown, G.D., Herre, J., Williams, D.L., Willment, J.A., Marshall, A.S., Gordon, S. (2003) Dectin-1 mediates the biological effects of beta-glucans. J Exp Med 197, 1119-24. 66. Bartels, M., Schweda, A.T., Dreikhausen, U., Frank, R., Resch, K., Beil, W., Nourbakhsh, M. (2007) Peptide-mediated disruption of NFκB/NRF interaction inhibits IL-8 gene activation by IL-1 or Helicobacter pylori. J Immunol 179, 7605-13. 67. Nourbakhsh, M., Kalble, S., Dorrie, A., Hauser, H., Resch, K., Kracht, M. (2001) The NF-κ b repressing factor is involved in basal repression and interleukin (IL)-1-induced activation of IL-8 transcription by binding to a conserved NF-κ b-flanking sequence element. J Biol Chem 276, 4501-8. 68. Backert, S., Moese, S., Selbach, M., Brinkmann, V., Meyer, T.F. (2001) Phosphorylation of tyrosine 972 of the Helicobacter pylori CagA protein is essential for induction of a scattering phenotype in gastric epithelial cells. Mol Microbiol 42, 631-44. 69. Segal, E.D., Cha, J., Lo, J., Falkow, S., Tompkins, L.S. (1999) Altered states: involvement of phosphorylated CagA in the induction of host cellular growth changes by Helicobacter pylori. Proc Natl Acad Sci U S A 96, 14559-64. 70. Hayden, M.S., Ghosh, S. (2004) Signaling to NF-κB. Genes Dev 18, 2195-224. 71. Holloway, A.F., Rao, S., Chen, X., Shannon, M.F. (2003) Changes in chromatin accessibility across the GM-CSF promoter upon T cell activation are dependent on nuclear factor κB proteins. J Exp Med 197, 413-23. 72. Tato, C.M., Mason, N., Artis, D., Shapira, S., Caamano, J.C., Bream, J.H., Liou, H.C., Hunter, C.A. (2006) Opposing roles of NF-κB family members in the regulation of NK cell proliferation and production of IFN-gamma. Int Immunol 18, 505-13. 73. Zhou, H., Wertz, I., O'Rourke, K., Ultsch, M., Seshagiri, S., Eby, M., Xiao, W., Dixit, V.M. (2004) BCL10 activates the NF-κB pathway through ubiquitination of NEMO. Nature 427, 167-71. 74. Zeng, H., Di, L., Fu, G., Chen, Y., Gao, X., Xu, L., Lin, X., Wen, R. (2007) Phosphorylation of BCL10 negatively regulates T-cell receptor-mediated NF-κB activation. Mol Cell Biol 27, 5235-45. 75. Gross, O., Grupp, C., Steinberg, C., Zimmermann, S., Strasser, D., Hannesschlager, N., Reindl, W., Jonsson, H., Huo, H., Littman, D.R., Peschel, C., Yokoyama, W.M., Krug, A., Ruland, J. (2008) Multiple ITAM-coupled NK-cell receptors engage the BCL10/MALT1 complex via CARMA1 for NF-κB and MAPK activation to selectively control cytokine production. Blood 112, 2421-8. 76. Gross, O., Grupp, C., Steinberg, C., Zimmermann, S., Strasser, D., Hannesschlager, N., Reindl, W., Peschel, C., Krug, A., Ruland, J. (2008) CARMA1/BCL10/MALT1 complexes transmit ITAM-coupled NK cell receptor signals for NF-κ B and MAPK activation. Wiener Klinische Wochenschrift 120, 21-21. 77. Amieva, M.R., Vogelmann, R., Covacci, A., Tompkins, L.S., Nelson, W.J., Falkow, S. (2003) Disruption of the epithelial apical-junctional complex by Helicobacter pylori CagA. Science 300, 1430-4. 78. Hara, H., Ishihara, C., Takeuchi, A., Xue, L., Morris, S.W., Penninger, J.M., Yoshida, H., Saito, T. (2008) Cell type-specific regulation of ITAM-mediated NF-κB activation by the adaptors, CARMA1 and CARD9. J Immunol 181, 918-30. 79. Martin, D., Galisteo, R., Gutkind, J.S. (2009) CXCL8/IL8 stimulates vascular endothelial growth factor (VEGF) expression and the autocrine activation of VEGFR2 in endothelial cells by activating NF-κB through the CBM (CARMA3/BCL10/MALT1) complex. J Biol Chem 284, 6038-42. 80. Matsumoto, R., Wang, D., Blonska, M., Li, H., Kobayashi, M., Pappu, B., Chen, Y., Lin, X. (2005) Phosphorylation of CARMA1 plays a critical role in T Cell receptor-mediated NF-κB activation. Immunity 23, 575-85. 81. Sommer, K., Guo, B., Pomerantz, J.L., Bandaranayake, A.D., Moreno-Garcia, M.E., Ovechkina, Y.L., Rawlings, D.J. (2005) Phosphorylation of the CARMA1 linker controls NF-κB activation. Immunity 23, 561-74. 82. Wang, D., You, Y., Case, S.M., McAllister-Lucas, L.M., Wang, L., DiStefano, P.S., Nunez, G., Bertin, J., Lin, X. (2002) A requirement for CARMA1 in TCR-induced NF-κ B activation. Nat Immunol 3, 830-5. 83. Khoshnan, A., Bae, D., Tindell, C.A., Nel, A.E. (2000) The physical association of protein kinase C theta with a lipid raft-associated inhibitor of κ B factor kinase (IKK) complex plays a role in the activation of the NF-κB cascade by TCR and CD28. J Immunol 165, 6933-40. | |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/9104 | - |
| dc.description.abstract | 轉錄因子NF-κB是調控淋巴球的活化中最主要的角色，其作用包括促進淋巴球的增生、分化以及細胞激素的製造。近年來的研究陸續指出，CBM complex(CARMA1-BCL10-MALT1)參與調控抗原受體活化NF-κB的路徑中。在實驗室先前的研究與Rebeaud, F. et al. (2008)的研究中，發現在淋巴球活化後，BCL10有被誘導切割的現象，而這個動作可能是透過類似caspase的para-caspase MALT1所造成。除了淋巴球之外，最近也有許多研究陸續證明CBM complex也參與在一些ITAM(immunoreceptor tyrosine-based activation motif)-containing receptor、TLR(Toll-like receptor)或GPCR(G protein-coupled receptors)所活化的NF-κB路徑中，雖然越來越多的研究探討BCL10在NF-κB活化路徑的調控，但對於BCL10切割的機制或者是否還有其他生理上的意義上的研究則付之闕如。因此我們試圖建立不同細胞活化NF-κB的模組，想要知道其他細胞活化NF-κB的路徑是否也有CBM complex的參與，並且觀察BCL10是否有發生被誘導切割的現象，來找出BCL10切割的機制以及其在生物中意義。
我的研究方法是利用各種刺激物(PMA/ionomycin、TNF-α、LPS、zymosan、IL-1β、Helicobacter pylori)來刺激不同細胞(淋巴系細胞：Jurkat 、Raji、Akata、NK，骨髓系細胞：Raw264.7、THP-1，非血球系細胞：HeLa、AGS、293T)用以活化NF-κB。我們以IκBα的降解以及冷光酵素測定法觀察NF-κB活化的狀況，並以免疫沈澱法將BCL10沈澱下來再以磷酸水解酶處理，觀察BCL10切割的情形。當刺激物活化NF-κB路徑，但不見BCL10的變化時，使用核酸干擾BCL10來驗證BCL10是否參與在活化路徑中。最後再以NF-κB抑制劑(MG132、Bay11-7085)以及鈣離子螯合劑(BAPTA-AM)，在Jurkat細胞中觀察對BCL10切割的影響，找出調控BCL10切割的因子。 本研究結果發現BCL10的切割只發生在T細胞、B細胞以及自然殺手細胞中，而TNF-α及IL-1β所誘導的NF-κB活化路徑中不需要BCL10的參與。雖然BCL10-MALT1存在於許多細胞中，但是MALT1在NF-κB活化時所誘導BCL10的切割卻不是一個共通的現象，顯示此切割的行為還需要MALT1以外的因子參與。當我們將Jurkat細胞以NF-κB抑制劑前處理後，再以PMA/ionomycin刺激，發現經MG132(抑制IκBα的降解)前處理之後並不影響BCL10的切割，但是經Bay11-7085(抑制IκBα的磷酸化)前處理過後的細胞，其BCL10的切割有被抑制的現象，顯示IKK的活性可能是造成BCL10切割的原因。最後我們以鈣離子螯合劑(BAPTA-AM)使細胞內鈣離子濃度降低，可以發現NF-κB的活化以及BCL10的切割有被抑制的情況，顯示鈣離子可以幫助BCL10的切割以及NF-κB的活化。 由於不同細胞以不同的CARD-containing adaptor組合成CBM complex來活化NF-κB的路徑(例如T細胞、B細胞以及NK細胞所使用的是CARMA1，骨髓系細胞所使用的是CARD9)，因此BCL10的切割可能與CARMA1的選用有關。CRAMA1與CARD9在蛋白質構造上的差異在於CARD9缺少了linker以及MAGUK domain，這個差異性使CARD-containing adaptor在活化上的調控有很大的不同，而這個調控的不同可能就是造成BCL10切割與否的關鍵。先前在實驗室的研究顯示磷酸化的BCL10更容易被MALT1所誘導切割，在Zeng, H. et al.(2007)的研究也指出IKKβ具有將BCL10磷酸化的能力，進而使之降解而抑制NF-κB的活化。因此我們推論，BCL10切割的機制可能與調控CARMA1-BCL10-MALT1 complex的活化有關，透過CBM complex活化IKK complex後，以IKKβ的活性將BCL10磷酸化而使之造成切割的結果，而鈣離子可能透過某種機制協助參與切割的調控當中，至於BCL10切割在生物中所扮演的角色仍是值得繼續探討的部分。 | zh_TW |
| dc.description.provenance | Made available in DSpace on 2021-05-20T20:09:22Z (GMT). No. of bitstreams: 1 ntu-98-R95445117-1.pdf: 2390756 bytes, checksum: 8d16f9fb46ef81e5f071c8ae5408aef8 (MD5) Previous issue date: 2009 | en |
| dc.description.tableofcontents | 目錄
口試委員審定書……………………………………………………………………Ⅰ 中文摘要……………………………………………………………………………Ⅱ 英文摘要……………………………………………………………………………Ⅴ 第一章、 序論…………………………………………………………………… 1 1.1 CBM complex個論…………………………………………………… 1 1.2 CBM complex在後天免疫訊息傳遞中的角色……………………… 8 1.3 CBM complex在先天免疫以及非免疫的訊息傳遞………………… 10 第二章、 研究目的……………………………………………………………… 11 第三章、 材料與方法…………………………………………………………… 12 第四章、 結果…………………………………………………………………… 21 4.1 建立各種細胞活化NF-κB路徑的模組……………………………… 21 4.1.1 淋巴球系血球細胞……………………………………………… 21 4.1.2 骨髓系血球細胞………………………………………………… 22 4.1.3 非血球系細胞…………………………………………………… 23 4.1.4 自然殺手細胞…………………………………………………… 24 4.2 BCL10切割的機制…………………………………………………… 24 4.2.1 IKK的活性參與BCL10切割的機制…………………………… 24 4.2.2 鈣離子(Calcium)參與BCL10切割的機制……………………… 25 第五章、 討論…………………………………………………………………… 27 5.1 BCL10的切割需要MALT1以及額外因子的參與…………………… 27 5.2 CARMA1-BCL10-MALT1的選用可能是造成切割的原因………… 27 5.3 CARD domain的遮蔽造成選用的差異………………………………...30 5.4 CARMA1與CARD9的功能性比較………………………………… ..30 5.5 IKK對於BCL10切割的重要性……………………………………… .31 5.6 BCL10切割的功能與意義………………………………………………32 第六章、 參考文獻……………………………………………………………… .33 圖表…………………………………………………………………………………41 附圖………………………………………………………………………………….56 | |
| dc.language.iso | zh-TW | |
| dc.title | BCL10切割機制之探討 | zh_TW |
| dc.title | Investigation on the Mechanisms of BCL10 cleavage | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 97-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 李財坤(Tsai-Kun Li),陳青周(Ching-Chow Chen) | |
| dc.subject.keyword | CARMA1,CARD9,BCL10,MALT1,NF-κB活化, | zh_TW |
| dc.subject.keyword | CARMA1,CARD9,BCL10,MALT1,NF-κB activation, | en |
| dc.relation.page | 59 | |
| dc.rights.note | 同意授權(全球公開) | |
| dc.date.accepted | 2009-07-30 | |
| 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 | |
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