請用此 Handle URI 來引用此文件:
http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/55355
完整後設資料紀錄
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.advisor | 嚴仲陽 | |
dc.contributor.author | Kun-Chin Ho | en |
dc.contributor.author | 何昆瑾 | zh_TW |
dc.date.accessioned | 2021-06-16T03:58:11Z | - |
dc.date.available | 2015-03-12 | |
dc.date.copyright | 2015-03-12 | |
dc.date.issued | 2014 | |
dc.date.submitted | 2014-12-01 | |
dc.identifier.citation | 1. Love PE, Bhandoola A. Signal integration and crosstalk during thymocyte migration and emigration. Nature reviews Immunology 2011 Jul; 11(7): 469-477.
2. Takahama Y. Journey through the thymus: stromal guides for T-cell development and selection. Nature reviews Immunology 2006 Feb; 6(2): 127-135. 3. Allman D, Sambandam A, Kim S, Miller JP, Pagan A, Well D, et al. Thymopoiesis independent of common lymphoid progenitors. Nature immunology 2003 Feb; 4(2): 168-174. 4. Feyerabend TB, Terszowski G, Tietz A, Blum C, Luche H, Gossler A, et al. Deletion of Notch1 converts pro-T cells to dendritic cells and promotes thymic B cells by cell-extrinsic and cell-intrinsic mechanisms. Immunity 2009 Jan 16; 30(1): 67-79. 5. Bell JJ, Bhandoola A. The earliest thymic progenitors for T cells possess myeloid lineage potential. Nature 2008 Apr 10; 452(7188): 764-767. 6. Ceredig R, Rolink T. A positive look at double-negative thymocytes. Nature reviews Immunology 2002 Nov; 2(11): 888-897. 7. Rodewald HR, Kretzschmar K, Swat W, Takeda S. Intrathymically expressed c-kit ligand (stem cell factor) is a major factor driving expansion of very immature thymocytes in vivo. Immunity 1995 Sep; 3(3): 313-319. 8. Peschon JJ, Morrissey PJ, Grabstein KH, Ramsdell FJ, Maraskovsky E, Gliniak BC, et al. Early lymphocyte expansion is severely impaired in interleukin 7 receptor-deficient mice. The Journal of experimental medicine 1994 Nov 1; 180(5): 1955-1960. 9. von Freeden-Jeffry U, Vieira P, Lucian LA, McNeil T, Burdach SE, Murray R. Lymphopenia in interleukin (IL)-7 gene-deleted mice identifies IL-7 as a nonredundant cytokine. The Journal of experimental medicine 1995 Apr 1; 181(4): 1519-1526. 10. Li WQ, Jiang Q, Khaled AR, Keller JR, Durum SK. Interleukin-7 inactivates the pro-apoptotic protein Bad promoting T cell survival. The Journal of biological chemistry 2004 Jul 9; 279(28): 29160-29166. 11. Khaled AR, Kim K, Hofmeister R, Muegge K, Durum SK. Withdrawal of IL-7 induces Bax translocation from cytosol to mitochondria through a rise in intracellular pH. Proceedings of the National Academy of Sciences of the United States of America 1999 Dec 7; 96(25): 14476-14481. 12. Kondo M, Akashi K, Domen J, Sugamura K, Weissman IL. Bcl-2 rescues T lymphopoiesis, but not B or NK cell development, in common gamma chain-deficient mice. Immunity 1997 Jul; 7(1): 155-162. 13. Pellegrini M, Bouillet P, Robati M, Belz GT, Davey GM, Strasser A. Loss of Bim increases T cell production and function in interleukin 7 receptor-deficient mice. The Journal of experimental medicine 2004 Nov 1; 200(9): 1189-1195. 14. Dunkle A, Dzhagalov I, He YW. Mcl-1 promotes survival of thymocytes by inhibition of Bak in a pathway separate from Bcl-2. Cell death and differentiation 2010 Jun; 17(6): 994-1002. 15. Hernandez JB, Newton RH, Walsh CM. Life and death in the thymus--cell death signaling during T cell development. Current opinion in cell biology 2010 Dec; 22(6): 865-871. 16. Fehling HJ, Krotkova A, Saint-Ruf C, von Boehmer H. Crucial role of the pre-T-cell receptor alpha gene in development of alpha beta but not gamma delta T cells. Nature 1995 Jun 29; 375(6534): 795-798. 17. Mandal M, Borowski C, Palomero T, Ferrando AA, Oberdoerffer P, Meng F, et al. The BCL2A1 gene as a pre-T cell receptor-induced regulator of thymocyte survival. The Journal of experimental medicine 2005 Feb 21; 201(4): 603-614. 18. Juntilla MM, Wofford JA, Birnbaum MJ, Rathmell JC, Koretzky GA. Akt1 and Akt2 are required for alphabeta thymocyte survival and differentiation. Proceedings of the National Academy of Sciences of the United States of America 2007 Jul 17; 104(29): 12105-12110. 19. Trampont PC, Tosello-Trampont AC, Shen Y, Duley AK, Sutherland AE, Bender TP, et al. CXCR4 acts as a costimulator during thymic beta-selection. Nature immunology 2010 Feb; 11(2): 162-170. 20. Newton K, Harris AW, Strasser A. FADD/MORT1 regulates the pre-TCR checkpoint and can function as a tumour suppressor. The EMBO journal 2000 Mar 1; 19(5): 931-941. 21. Singer A, Adoro S, Park JH. Lineage fate and intense debate: myths, models and mechanisms of CD4- versus CD8-lineage choice. Nature reviews Immunology 2008 Oct; 8(10): 788-801. 22. Sun Z, Unutmaz D, Zou YR, Sunshine MJ, Pierani A, Brenner-Morton S, et al. Requirement for RORgamma in thymocyte survival and lymphoid organ development. Science 2000 Jun 30; 288(5475): 2369-2373. 23. Bouillet P, Metcalf D, Huang DC, Tarlinton DM, Kay TW, Kontgen F, et al. Proapoptotic Bcl-2 relative Bim required for certain apoptotic responses, leukocyte homeostasis, and to preclude autoimmunity. Science 1999 Nov 26; 286(5445): 1735-1738. 24. Bouillet P, Purton JF, Godfrey DI, Zhang LC, Coultas L, Puthalakath H, et al. BH3-only Bcl-2 family member Bim is required for apoptosis of autoreactive thymocytes. Nature 2002 Feb 21; 415(6874): 922-926. 25. Smith-Garvin JE, Koretzky GA, Jordan MS. T cell activation. Annual review of immunology 2009; 27: 591-619. 26. Fischer AM, Katayama CD, Pages G, Pouyssegur J, Hedrick SM. The role of erk1 and erk2 in multiple stages of T cell development. Immunity 2005 Oct; 23(4): 431-443. 27. Sohn SJ, Lewis GM, Winoto A. Non-redundant function of the MEK5-ERK5 pathway in thymocyte apoptosis. The EMBO journal 2008 Jul 9; 27(13): 1896-1906. 28. Matloubian M, Lo CG, Cinamon G, Lesneski MJ, Xu Y, Brinkmann V, et al. Lymphocyte egress from thymus and peripheral lymphoid organs is dependent on S1P receptor 1. Nature 2004 Jan 22; 427(6972): 355-360. 29. Itoh M, Takahashi T, Sakaguchi N, Kuniyasu Y, Shimizu J, Otsuka F, et al. Thymus and autoimmunity: production of CD25+CD4+ naturally anergic and suppressive T cells as a key function of the thymus in maintaining immunologic self-tolerance. J Immunol 1999 May 1; 162(9): 5317-5326. 30. Hori S, Nomura T, Sakaguchi S. Control of regulatory T cell development by the transcription factor Foxp3. Science 2003 Feb 14; 299(5609): 1057-1061. 31. Fontenot JD, Gavin MA, Rudensky AY. Foxp3 programs the development and function of CD4+CD25+ regulatory T cells. Nature immunology 2003 Apr; 4(4): 330-336. 32. Khattri R, Cox T, Yasayko SA, Ramsdell F. An essential role for Scurfin in CD4+CD25+ T regulatory cells. Nature immunology 2003 Apr; 4(4): 337-342. 33. Workman CJ, Szymczak-Workman AL, Collison LW, Pillai MR, Vignali DA. The development and function of regulatory T cells. Cellular and molecular life sciences : CMLS 2009 Aug; 66(16): 2603-2622. 34. Marks BR, Nowyhed HN, Choi JY, Poholek AC, Odegard JM, Flavell RA, et al. Thymic self-reactivity selects natural interleukin 17-producing T cells that can regulate peripheral inflammation. Nature immunology 2009 Oct; 10(10): 1125-1132. 35. Gapin L, Matsuda JL, Surh CD, Kronenberg M. NKT cells derive from double-positive thymocytes that are positively selected by CD1d. Nature immunology 2001 Oct; 2(10): 971-978. 36. Chun T, Page MJ, Gapin L, Matsuda JL, Xu H, Nguyen H, et al. CD1d-expressing dendritic cells but not thymic epithelial cells can mediate negative selection of NKT cells. The Journal of experimental medicine 2003 Apr 7; 197(7): 907-918. 37. Kronenberg M. Toward an understanding of NKT cell biology: progress and paradoxes. Annual review of immunology 2005; 23: 877-900. 38. Stritesky GL, Jameson SC, Hogquist KA. Selection of self-reactive T cells in the thymus. Annual review of immunology 2012; 30: 95-114. 39. Cheroutre H, Lambolez F, Mucida D. The light and dark sides of intestinal intraepithelial lymphocytes. Nature reviews Immunology 2011 Jul; 11(7): 445-456. 40. Hayday A, Tigelaar R. Immunoregulation in the tissues by gammadelta T cells. Nature reviews Immunology 2003 Mar; 3(3): 233-242. 41. Ciofani M, Zuniga-Pflucker JC. Determining gammadelta versus alphass T cell development. Nature reviews Immunology 2010 Sep; 10(9): 657-663. 42. Melichar HJ, Narayan K, Der SD, Hiraoka Y, Gardiol N, Jeannet G, et al. Regulation of gammadelta versus alphabeta T lymphocyte differentiation by the transcription factor SOX13. Science 2007 Jan 12; 315(5809): 230-233. 43. Haks MC, Lefebvre JM, Lauritsen JP, Carleton M, Rhodes M, Miyazaki T, et al. Attenuation of gammadeltaTCR signaling efficiently diverts thymocytes to the alphabeta lineage. Immunity 2005 May; 22(5): 595-606. 44. Hayes SM, Li L, Love PE. TCR signal strength influences alphabeta/gammadelta lineage fate. Immunity 2005 May; 22(5): 583-593. 45. Prinz I, Silva-Santos B, Pennington DJ. Functional development of gammadelta T cells. European journal of immunology 2013 Aug; 43(8): 1988-1994. 46. Broughton SE, Dhagat U, Hercus TR, Nero TL, Grimbaldeston MA, Bonder CS, et al. The GM-CSF/IL-3/IL-5 cytokine receptor family: from ligand recognition to initiation of signaling. Immunological reviews 2012 Nov; 250(1): 277-302. 47. Lopez AF, Hercus TR, Ekert P, Littler DR, Guthridge M, Thomas D, et al. Molecular basis of cytokine receptor activation. IUBMB life 2010 Jul; 62(7): 509-518. 48. Murakami M, Narazaki M, Hibi M, Yawata H, Yasukawa K, Hamaguchi M, et al. Critical cytoplasmic region of the interleukin 6 signal transducer gp130 is conserved in the cytokine receptor family. Proceedings of the National Academy of Sciences of the United States of America 1991 Dec 15; 88(24): 11349-11353. 49. Tanner JW, Chen W, Young RL, Longmore GD, Shaw AS. The conserved box 1 motif of cytokine receptors is required for association with JAK kinases. The Journal of biological chemistry 1995 Mar 24; 270(12): 6523-6530. 50. Miura O, Ihle JN. Subunit structure of the erythropoietin receptor analyzed by 125I-Epo cross-linking in cells expressing wild-type or mutant receptors. Blood 1993 Apr 1; 81(7): 1739-1744. 51. Kao CJ, Chiang YJ, Chen PH, Lin KR, Hwang PI, Yang-Yen HF, et al. CBAP interacts with the un-liganded common beta-subunit of the GM-CSF/IL-3/IL-5 receptor and induces apoptosis via mitochondrial dysfunction. Oncogene 2008 Feb 28; 27(10): 1397-1403. 52. Yamada R, Mizutani-Koseki Y, Koseki H, Takahashi N. Requirement for Mab21l2 during development of murine retina and ventral body wall. Developmental biology 2004 Oct 15; 274(2): 295-307. 53. Jin J, Smith FD, Stark C, Wells CD, Fawcett JP, Kulkarni S, et al. Proteomic, functional, and domain-based analysis of in vivo 14-3-3 binding proteins involved in cytoskeletal regulation and cellular organization. Current biology : CB 2004 Aug 24; 14(16): 1436-1450. 54. Uberti B, Dentelli P, Rosso A, Defilippi P, Brizzi MF. Inhibition of beta1 integrin and IL-3Rbeta common subunit interaction hinders tumour angiogenesis. Oncogene 2010 Dec 16; 29(50): 6581-6590. 55. Defilippi P, Rosso A, Dentelli P, Calvi C, Garbarino G, Tarone G, et al. {beta}1 Integrin and IL-3R coordinately regulate STAT5 activation and anchorage-dependent proliferation. The Journal of cell biology 2005 Mar 28; 168(7): 1099-1108. 56. Chiang YJ, Ho KC, Sun CT, Chiu JJ, Lee FJ, Liao F, et al. CBAP functions as a novel component in chemokine-induced ZAP70-mediated T-cell adhesion and migration. PloS one 2013; 8(4): e61761. 57. Darragh J, Soloaga A, Beardmore VA, Wingate AD, Wiggin GR, Peggie M, et al. MSKs are required for the transcription of the nuclear orphan receptors Nur77, Nurr1 and Nor1 downstream of MAPK signalling. The Biochemical journal 2005 Sep 15; 390(Pt 3): 749-759. 58. Boley SE, Wong VA, French JE, Recio L. p53 heterozygosity alters the mRNA expression of p53 target genes in the bone marrow in response to inhaled benzene. Toxicological sciences : an official journal of the Society of Toxicology 2002 Apr; 66(2): 209-215. 59. Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods 2001 Dec; 25(4): 402-408. 60. Mohtashami M, Shah DK, Nakase H, Kianizad K, Petrie HT, Zuniga-Pflucker JC. Direct comparison of Dll1- and Dll4-mediated Notch activation levels shows differential lymphomyeloid lineage commitment outcomes. J Immunol 2010 Jul 15; 185(2): 867-876. 61. Kortum RL, Sommers CL, Pinski JM, Alexander CP, Merrill RK, Li W, et al. Deconstructing Ras signaling in the thymus. Molecular and cellular biology 2012 Jul; 32(14): 2748-2759. 62. Cao Y, Li H, Liu H, Zhang M, Hua Z, Ji H, et al. LKB1 regulates TCR-mediated PLCgamma1 activation and thymocyte positive selection. The EMBO journal 2011 May 18; 30(10): 2083-2093. 63. Wange RL, Kong AN, Samelson LE. A tyrosine-phosphorylated 70-kDa protein binds a photoaffinity analogue of ATP and associates with both the zeta chain and CD3 components of the activated T cell antigen receptor. The Journal of biological chemistry 1992 Jun 15; 267(17): 11685-11688. 64. Nitta T, Nitta S, Lei Y, Lipp M, Takahama Y. CCR7-mediated migration of developing thymocytes to the medulla is essential for negative selection to tissue-restricted antigens. Proceedings of the National Academy of Sciences of the United States of America 2009 Oct 6; 106(40): 17129-17133. 65. Kisielow P, Teh HS, Bluthmann H, von Boehmer H. Positive selection of antigen-specific T cells in thymus by restricting MHC molecules. Nature 1988 Oct 20; 335(6192): 730-733. 66. Clarke SR, Barnden M, Kurts C, Carbone FR, Miller JF, Heath WR. Characterization of the ovalbumin-specific TCR transgenic line OT-I: MHC elements for positive and negative selection. Immunology and cell biology 2000 Apr; 78(2): 110-117. 67. von Boehmer H. Developmental biology of T cells in T cell-receptor transgenic mice. Annual review of immunology 1990; 8: 531-556. 68. Benz C, Heinzel K, Bleul CC. Homing of immature thymocytes to the subcapsular microenvironment within the thymus is not an absolute requirement for T cell development. European journal of immunology 2004 Dec; 34(12): 3652-3663. 69. Davalos-Misslitz AC, Worbs T, Willenzon S, Bernhardt G, Forster R. Impaired responsiveness to T-cell receptor stimulation and defective negative selection of thymocytes in CCR7-deficient mice. Blood 2007 Dec 15; 110(13): 4351-4359. 70. Starr TK, Jameson SC, Hogquist KA. Positive and negative selection of T cells. Annual review of immunology 2003; 21: 139-176. 71. Gong Q, Cheng AM, Akk AM, Alberola-Ila J, Gong G, Pawson T, et al. Disruption of T cell signaling networks and development by Grb2 haploid insufficiency. Nature immunology 2001 Jan; 2(1): 29-36. 72. Bennett BL, Sasaki DT, Murray BW, O'Leary EC, Sakata ST, Xu W, et al. SP600125, an anthrapyrazolone inhibitor of Jun N-terminal kinase. Proceedings of the National Academy of Sciences of the United States of America 2001 Nov 20; 98(24): 13681-13686. 73. Lei K, Davis RJ. JNK phosphorylation of Bim-related members of the Bcl2 family induces Bax-dependent apoptosis. Proceedings of the National Academy of Sciences of the United States of America 2003 Mar 4; 100(5): 2432-2437. 74. Putcha GV, Le S, Frank S, Besirli CG, Clark K, Chu B, et al. JNK-mediated BIM phosphorylation potentiates BAX-dependent apoptosis. Neuron 2003 Jun 19; 38(6): 899-914. 75. McCarty N, Paust S, Ikizawa K, Dan I, Li X, Cantor H. Signaling by the kinase MINK is essential in the negative selection of autoreactive thymocytes. Nature immunology 2005 Jan; 6(1): 65-72. 76. Villunger A, Marsden VS, Zhan Y, Erlacher M, Lew AM, Bouillet P, et al. Negative selection of semimature CD4(+)8(-)HSA+ thymocytes requires the BH3-only protein Bim but is independent of death receptor signaling. Proceedings of the National Academy of Sciences of the United States of America 2004 May 4; 101(18): 7052-7057. 77. Molina TJ, Kishihara K, Siderovski DP, van Ewijk W, Narendran A, Timms E, et al. Profound block in thymocyte development in mice lacking p56lck. Nature 1992 May 14; 357(6374): 161-164. 78. Negishi I, Motoyama N, Nakayama K, Senju S, Hatakeyama S, Zhang Q, et al. Essential role for ZAP-70 in both positive and negative selection of thymocytes. Nature 1995 Aug 3; 376(6539): 435-438. 79. Zhang W, Sommers CL, Burshtyn DN, Stebbins CC, DeJarnette JB, Trible RP, et al. Essential role of LAT in T cell development. Immunity 1999 Mar; 10(3): 323-332. 80. Fu G, Vallee S, Rybakin V, McGuire MV, Ampudia J, Brockmeyer C, et al. Themis controls thymocyte selection through regulation of T cell antigen receptor-mediated signaling. Nature immunology 2009 Aug; 10(8): 848-856. 81. Johnson AL, Aravind L, Shulzhenko N, Morgun A, Choi SY, Crockford TL, et al. Themis is a member of a new metazoan gene family and is required for the completion of thymocyte positive selection. Nature immunology 2009 Aug; 10(8): 831-839. 82. Lesourne R, Uehara S, Lee J, Song KD, Li L, Pinkhasov J, et al. Themis, a T cell-specific protein important for late thymocyte development. Nature immunology 2009 Aug; 10(8): 840-847. 83. Wang D, Zheng M, Lei L, Ji J, Yao Y, Qiu Y, et al. Tespa1 is involved in late thymocyte development through the regulation of TCR-mediated signaling. Nature immunology 2012 Jun; 13(6): 560-568. 84. Ogawa M, Okamura T, Ishikura S, Doi K, Matsuzaki H, Tanaka Y, et al. Zfat-deficiency results in a loss of CD3zeta phosphorylation with dysregulation of ERK and Egr activities leading to impaired positive selection. PloS one 2013; 8(10): e76254. 85. Hwang PM, Li C, Morra M, Lillywhite J, Muhandiram DR, Gertler F, et al. A 'three-pronged' binding mechanism for the SAP/SH2D1A SH2 domain: structural basis and relevance to the XLP syndrome. The EMBO journal 2002 Feb 1; 21(3): 314-323. 86. Tan YX, Manz BN, Freedman TS, Zhang C, Shokat KM, Weiss A. Inhibition of the kinase Csk in thymocytes reveals a requirement for actin remodeling in the initiation of full TCR signaling. Nature immunology 2013 Dec 8. 87. Choi YI, Duke-Cohan JS, Chen W, Liu B, Rossy J, Tabarin T, et al. Dynamic control of beta1 integrin adhesion by the plexinD1-sema3E axis. Proceedings of the National Academy of Sciences of the United States of America 2014 Jan 7; 111(1): 379-384. 88. Ueno T, Saito F, Gray DH, Kuse S, Hieshima K, Nakano H, et al. CCR7 signals are essential for cortex-medulla migration of developing thymocytes. The Journal of experimental medicine 2004 Aug 16; 200(4): 493-505. 89. Schneider OD, Weiss AA, Miller WE. Pertussis toxin signals through the TCR to initiate cross-desensitization of the chemokine receptor CXCR4. J Immunol 2009 May 1; 182(9): 5730-5739. 90. Yasuda T, Kuwabara T, Nakano H, Aritomi K, Onodera T, Lipp M, et al. Chemokines CCL19 and CCL21 promote activation-induced cell death of antigen-responding T cells. Blood 2007 Jan 15; 109(2): 449-456. 91. Liston A, Enders A, Siggs OM. Unravelling the association of partial T-cell immunodeficiency and immune dysregulation. Nature reviews Immunology 2008 Jul; 8(7): 545-558. | |
dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/55355 | - |
dc.description.abstract | T細胞受器所傳遞之訊息對胸腺細胞於CD4與CD8分子雙陽性之發育時期是非常關鍵的,但是參與其中的分子尚未完全被鑑定與分析。於先前的研究中,本實驗室已發現GM-CSF/IL-3/IL-5 receptor common β-chain associated protein (CBAP)會調控由受體缺乏所引起的細胞凋亡與由ZAP70所傳達的T細胞移動,而本研究旨在進一步探討CBAP於T細胞譜系中的功能。基於CBAP在胸腺細胞中的高表現量,本研究使用CBAP基因剃除小鼠探討該基因於胸腺發育時的功能。CBAP基因剃除小鼠的早期胸腺細胞發育與正向篩選能力無明顯缺陷;然而,在數種檢測負向篩選能力的動物模式中(包含利用T細胞受器轉基因鼠、施打抗CD3抗體與施打超抗原staphylococcal enterotoxin B等),T細胞受器所誘導之胸腺細胞死亡則顯著地下降。這與在CBAP基因剃除之胸腺細胞中,T細胞受器所誘導之BIM蛋白累積量較少有高度的關聯。進一步的研究發現在缺少CBAP時,T細胞受器近端如ZAP70、LAT與PLCγ1與遠端如JNK之訊息傳遞皆變弱,而且LAT訊息傳遞複合體之形成也較不完全。這些證據顯示CBAP是一個參與在T細胞受器訊息傳遞中的新穎分子,並在胸腺細胞的負向篩選中調控其死亡。此外,藉由酵母菌雙雜合系統找尋與CBAP有交互作的蛋白顯示,CBAP有可能參與許多類型的生物進程,這項結果也呼應了本研究與本實驗室先前的研究:CBAP在數種不同的生理反應中均扮演調控的角色。 | zh_TW |
dc.description.abstract | T cell receptor (TCR)-transduced signaling is critical to thymocyte development at the CD4/CD8 double-positive stage, but the molecules involved in this process are not yet fully characterized. Our laboratory previously demonstrated that GM-CSF/IL-3/IL-5 receptor common β-chain associated protein (CBAP) modulates cytokine withdrawal-induced apoptosis in vitro and ZAP70-mediated T cell migration/adhesion in vivo. In this study, the function of CBAP in T cell lineage was further investigated. Based on the high expression of CBAP during thymocyte development, a CBAP knockout mouse was utilized to investigate the function of CBAP in thymocyte development. CBAP-deficient mice showed normal early thymocyte development and positive selection. In contrast, several negative selection models (including TCR transgene, superantigen staphylococcal enterotoxin B, and anti-CD3 antibody treatment) revealed an attenuation of TCR-induced thymocyte deletion in CBAP knockout mice. This phenotype correlated with a reduced accumulation of BIM upon TCR crosslinking in CBAP-deficient thymocytes. Loss of CBAP led to reduced TCR-induced phosphorylation of proteins involved in both proximal and distal signaling events, including ZAP70, LAT, PLCγ1, and JNK1/2. Furthur investigation on TCR proximal signaling revealed that TCR-induced association of LAT signalosome components is reduced in CBAP-deficient thymocytes. These data demonstrate that CBAP is a novel component in the TCR signaling pathway and modulates thymocyte apoptosis during negative selection. Moreover, CBAP-interacting proteins identified by a yeast two-hybrid system implied that CBAP is involved in divergent biological processes, echoing multiple functions of CBAP characterized in the previous and present studies. | en |
dc.description.provenance | Made available in DSpace on 2021-06-16T03:58:11Z (GMT). No. of bitstreams: 1 ntu-103-D97448003-1.pdf: 2513432 bytes, checksum: 44d3ce2254c99ba4cf06b05c5378696a (MD5) Previous issue date: 2014 | en |
dc.description.tableofcontents | 中文摘要-i
Abstract-ii Table of contents -iv 1.Introduction-p1 1-1.T cell development-p1 1-1-1.Double-negative stage-p2 1-1-2.Double-positive stage and single positive stage-p4 1-1-3.Other T cell types generated from the thymus-p6 1-2.Common β-chain associated protein-p7 1-2-1.Discovery and feature of common β-chain associated protein-p8 1-2-2.Function of common β-chain associated protein in apoptosis and migration/adhesion-p9 2.Materials and methods-p12 3.Phenotype of CBAP-deficient mice in T cell development-p18 3-1.Results-p18 3-1-1.General analysis of CBAP-deficient thymi-p18 3-1-2.Migratory defects in CBAP-deficient thymocytes-p19 3-1-3.Early thymocyte development in CBAP-deficient mice-p20 3-1-4.Positive selection in CBAP-deficient mice-p22 3-1-5.Defective negative selection in CBAP-deficient mice-p22 3-2.Discussion-p24 4.Mechanism of CBAP in modulating negative selection-p33 4-1.Results-p33 4-1-1.Abatement of TCR-induced BIM expression and JNK phosphorylation in CBAP-deficient thymocytes-p33 4-1-2.Involvement of CBAP in TCR proximal signaling-p36 4-2.Discussion-p37 5.Identification of CBAP-interacting proteins-p44 5-1.Results-p44 5-1-1.Screening CBAP-interacting proteins by yeast two-hybrid-p44 5-1-2.Self-interaction of CBAP-p45 5-1-3.Interaction of CBAP and FLN A-p45 5-2.Discussion-p46 6.References-p52 | |
dc.language.iso | en | |
dc.title | CBAP蛋白於T細胞發育之功能研究 | zh_TW |
dc.title | Functional Analysis of CBAP in T Cell Development | en |
dc.type | Thesis | |
dc.date.schoolyear | 103-1 | |
dc.description.degree | 博士 | |
dc.contributor.oralexamcommittee | 李芳仁,賴明宗,楊性芳,廖南詩 | |
dc.subject.keyword | T細胞發育,負向篩選,T細胞受器訊息, | zh_TW |
dc.subject.keyword | T cell development,negative selection,TCR signaling, | en |
dc.relation.page | 62 | |
dc.rights.note | 有償授權 | |
dc.date.accepted | 2014-12-01 | |
dc.contributor.author-college | 醫學院 | zh_TW |
dc.contributor.author-dept | 分子醫學研究所 | zh_TW |
顯示於系所單位: | 分子醫學研究所 |
文件中的檔案:
檔案 | 大小 | 格式 | |
---|---|---|---|
ntu-103-1.pdf 目前未授權公開取用 | 2.45 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。