Molecular regulation of cytokine gene expression during the immune response

Journal of Clinical Immunology

Volumn 19, Issue 2, 1999, Pages 98-108

  Viola, João P B ^a   Rao, Anjana ^b  

^a INSTITUTO NACIONAL DE CÂNCER   (Brazil)

^b HARVARD MEDICAL SCHOOL   (United States)

Author keywords

Cytokine genes; Immune response; Molecular regulation

Indexed keywords

CD4 ANTIGEN; CYTOKINE; GAMMA INTERFERON; INTERLEUKIN 10; INTERLEUKIN 13; INTERLEUKIN 2; INTERLEUKIN 4; INTERLEUKIN 5; INTERLEUKIN 6;

ARTICLE; GENE EXPRESSION REGULATION; HELPER CELL; HUMAN; IMMUNOREACTIVITY; IMMUNOREGULATION; INTERFERON PRODUCTION; LYMPHOCYTE DIFFERENTIATION; NONHUMAN; PRIORITY JOURNAL; PROTEIN EXPRESSION;

EID: 0032922288     PISSN: 02719142     EISSN: None     Source Type: Journal    
DOI: 10.1023/A:1020502516196     Document Type: Article

References (129)

1. 1. Paul WE, Seder RA: Lymphocyte responses and cytokines. Cell 76:241-251, 1994
2. 2. Abbas AK, Murphy KM, Sher A: Functional diversity of helper T lymphocytes. Nature 383:787-793, 1996
3. 3. Carter LL, Dutton RW: Type 1 and type 2: A fundamental dichotomy for all T-cell subsets. Curr Opin Immunol 8:336-342, 1996
4. 4. Constant SL, Bottomly K: Induction of Th1 and Th2 CD4+ T cell responses: The alternative approaches. Annu Rev Immunol 15:297-322, 1997
5. 5. Rincon M, Flavell R: T-cell subsets: Transciptional control in the Th1/Th2 decision. Curr Biol 729-732, 1997
6. 6. Szabo S, Glimcher L, Ho I: Genes that regulate interleukin-4 expression in T cells. Curr Opin Immunol 9:776-781, 1998
7. 7. Murphy KM: T lymphocyte differentiation in the periphery. Curr Opin Immunol 10:226-232, 1998
8. 8. O'Garra A: Cytokines induce the development of functionally heterogeneous T helper cell subsets. Immunity 8:275-283, 1998
9. 9. Agarwal S, Rao A: Long-range transcriptional regulation of cytokine gene expression. Curr Opin Immunol 10:345-352, 1998
10. 10. Orkin SH: Regulation of globin gene expression in erythroid cells. Eur J Biochem 231:271-281, 1995
11. 11. Sleckman BP, Gorman JR, Alt FW: Accessibility control of antigen-receptor variable-region gene assembly: Role of cisacting elements. Annu Rev Immunol 14:459-481, 1996
12. 12. Kass SU, Pruss D, Wolffe AP: How does DNA methylation repress transcription? Trends Genet 13:444-449, 1997
13. 13. Kadonaga JT: Eukaryotic transcription: An interlaced network of transcription factors and chromatin-modifying machines. Cell 92:307-313, 1998
14. 14. Gerber AN, Klesert TR, Bergstrom DA, Tapscott SJ: Two domains of MyoD mediate transcriptional activation of genes in repressive chromatin: a mechanism for lineage determination in myogenesis. Genes Dev 11:436-450, 1997
15. 15. Stamatoyannopoulos JA, Goodwin A, Joyce T, Lowrey CH: NF-E2 and GATA binding motifs are required for the formation of DNase I hypersensitive site 4 of the human beta-globin locus control region. EMBO J 14:106-116, 1995
16. 16. Le Gros G, Ben-Sasson S, Seder R, Finkelman F, Paul WE: Generation of interleukin 4 (IL-4)-producing cells in vivo and in vitro: IL-2 and IL-4 are required for in vitro generation of IL-4-producing cells. J Exp Med 172:921-929, 1990
17. 17. Croft M, Swain S: Recently activated naive CD4 T cells can help resting B cells, and can produce sufficient autocrine IL-4 to drive differentiation to secretion of T helper 2-type cytokines. J Immunol 154:4269 4282, 1995
18. 18. Lederer J, Perez V, DesRoches L, Kim S, Abbas A, Lichtman A: Cytokine transcriptional events during helper T cell subset differentiation. J Exp Med 184:397-406, 1996
19. 19. Bucy RP, Karr L, Huang GQ, Li J, Carter D, Honjo K, Lemons JA, Murphy KM, Weaver CT: Single cell analysis of cytokine gene coexpression during CD4+ T-cell phenotype development. Proc Natl Acad Sci USA 92:7565-7569, 1995
20. 20. Young H, Ghosh P, Ye B, Jianping, Lederer J, Lichtman A, Gerard J, Penix L, Wilson C, Melvin A, McGurn M, Lewis D, Taub D: Differentiation of the T helper phenotypes by analysis of the methylation state of the IFN-γ gene. J Immunol 153:3603-3610, 1994
21. 21. Melvin A, McGurn M, Bort S, Gibson C, Lewis D: Hypomethylation of the interferon-γ gene correlates with its expression by primary T-lineage cells. Hypomethylation of the interferon-γ gene correlates with its expression by primary T-lineage cells. Eur J Immunol 25:426-430, 1995
22. 22. Fitzpatrick D, Shirley K, McDonald L, Bielefeldt-Ohmann H, Kay G, Kelso A: Distinct methylation of the interferon (IFN)-γ and interleukin 3 (IL-3) genes in newly activated primary CD8+ T lymphocytes: Regional IFN-γ promoter demethylation and mRNA expression are heritable in CD44 high CD8+ T cells. J Exp Med 188:103-117, 1998
23. 23. Bird JJ, Brown DR, Mullen AC, Moskowitz NH, Mahowald MA, Sider JR, Gajewski TF, Wang CR, Reiner SL: Helper T cell differentiation is controlled by the cell cycle. Immunity 9:229-237, 1998
24. 24. Hollander GA, Zuklys S, Morel C, Mizoguchi E, Mobisson K, Simpson S, Terhorst C, Wishart W, Golan DE, Bhan AK, Burakoff SJ: Monoallelic expression of the interleukin-2 locus. Science 279:2118-2121, 1998
25. 25. Riviere I, Sunshine MJ, Littman DR: Regulation of IL-4 expression by activation of individual alleles. Immunity 9:217-228, 1998
26. 26. Agarwal S, Rao A: Modulation of chromatin structure regulates cytokine gene expression during T cell differentiation. Immunity 9, in press (1998)
27. 27. Blank V, Andrews N: The Maf transcription factors: regulators of differentiation. Trends Biochem Sci 22:437-441, 1997
28. 28. Motohashi H, Shavit J, Igarashi K, Yamamoto M, Engel JD: The world according to Maf. Nucleic Acids Res 25:2953-2959, 1997
29. 29. Weiss M, Orkin S: GATA transcription factors: Key regulators of hematopoiesis. Exp Hematol 23:99-107, 1995
30. 30. Huang H, Paul WE: Impaired interleukin 4 signaling in T helper type 1 cells. J Exp Med 187:1305-1313, 1998
31. 31. Bluestone JA: New perspectives of CD28-B7-mediated T cell costimulation. Immunity 2:555-559, 1995
32. 32. Schindler C, Darnell JE Jr: Transcriptional responses to polypeptide ligands: the JAK-STAT pathway. Annu Rev Biochem 64: 621-651, 1995
33. 33. Leonard WJ, Os JJ: Jaks and STATs: Biological implications. Annu Rev Immunol 16:293-322, 1998
34. 34. Liu KD, Gaffen SL, Goldsmith MA: JAK/STAT signaling by cytokine receptors. Curr Opin Immunol 10:271-278, 1998
35. 35. Durbin JE, Hackenmiller R, Simon MC, Levy DE: Targeted disruption of the mouse Stat1 gene results in compromised innate immunity to viral disease. Cell 84:443-450, 1996
36. 36. Meraz MA, White JM, Sheehan KC, Bach EA, Rodig SJ, Dighe AS, Kaplan DH, Riley JK, Greenlund AC, Campbell D, Carver-Moore K, DuBois RN, Clark R, Aguet M, Schreiber RD: Targeted disruption of the Stat1 gene in mice reveals unexpected physiologic specificity in the JAK-STAT signaling pathway. Cell 84:431-442, 1996
37. 37. Takeda K, Noguchi K, Shi W, Tanaka T, Matsumoto M, Yoshida N, Kishimoto T, Akira S: Targeted disruption of the mouse Stat3 gene leads to early embryonic lethality. Proc Natl Acad Sci USA 94:3801-3804, 1997
38. 38. Liu B, Liao J, Rao X, Kushner SA, Chung CD, Chang DD, Shuai K: Inhibition of Stat1-mediated gene activation by PIAS1. Proc Natl Acad Sci USA 95:10626-10631, 1998
39. 39. Udy GB, Towers RP, Snell RG, Wilkins RJ, Park SH, Ram PA, Waxman DJ, Davey HW: Requirement of STAT5b for sexual dimorphism of body growth rates and liver gene expression. Proc Nad Acad Sci USA 94:7239-7244, 1997
40. 40. Teglund S, McKay C, Schuetz E, van Deursen JM, Stravopodis D, Wang D, Brown M, Bodner S, Grosveld G, Ihle JN: Stat5a and Stat5b proteins have essential and nonessential, or redundant, roles in cytokine responses. Cell 93:841-850, 1998
41. 41. Jacobson NG, Szabo SJ, Weber-Nordt RM, Zhong Z, Schreiber RD, Darnell JE Jr, Murphy KM: Interleukin 12 signaling in T helper type 1 (Th1) cells involves tyrosine phosphorylation of signal transducer and activator of transcription (Stat)3 and Stat4. J Exp Med 181:1755-1762, 1995
42. 42. Hou J, Schindler U, Henzel WJ, Ho TC, Brasseur M, McKnight SL: An interleukin-4-induced transcription factor: IL-4 Stat. Science 265:1701-1706, 1994
43. 43. Kopf M, Le Gros G, Bachmann M, Lamers MC, Bluethmann H, Kohler G: Disruption of the murine IL-4 gene blocks Th2 cytokine responses. Nature 362:245-248, 1993
44. 44. Kaplan MH, Sun YL, Hoey T, Grusby MJ: Impaired IL-12 responses and enhanced development of Th2 cells in Stat4-deficient mice. Nature 382:174-177, 1996
45. 45. Kaplan MH, Schindler U, Smiley ST, Grusby MJ: Stat6 is required for mediating responses to IL-4 and for development of Th2 cells. Immunity 4:313-319, 1996
46. 46. Magram J, Sfarra J, Connaughton S, Faherty D, Warrier R, Carvajal D, Wu CY, Stewart C, Sarmiento U, Gately MK: IL-12-deficient mice are defective but not devoid of type 1 cytokine responses. Ann NY Acad Sci 795:60-70, 1996
47. 47. Takeda K, Tanaka T, Shi W, Matsumoto M, Minami M, Kashiwamura S, Nakanishi K, Yoshida N, Kishimoto T, Akira S: Essential role of Stat6 in IL-4 signalling. Nature 380:627-630, 1996
48. 48. Thierfelder WE, van Deursen JM, Yamamoto K, Tripp RA, Sarawar SR, Carson RT, Sangster MY, Vignali DA, Doherty PC, Grosveld GC, Ihle JN: Requirement for Stat4 in interleukin-12-mediated responses of natural killer and T cells. Nature 382:171-174, 1996
49. 49. Shimoda K, van Deursen J, Sangster MY, Sarawar SR, Carson RT, Tripp RA, Chu C, Quelle FW, Nosaka T, Vignali DA, Doherty PC, Grosveld G, Paul WE, Ihle JN: Lack of IL-4-induced Th2 response and IgE class switching in mice with disrupted Stat6 gene. Nature 380:630-633, 1996
50. 50. Akimoto T, Numata F, Tamura M, Takata Y, Higashida N, Takashi T, Takeda K, Akira S: Abrogation of bronchial eosinophilic inflammation and airway hyperreactivity in signal transducers and activators of transcription (STAT)6-deficient mice. J Exp Med 187:1537-1542, 1998
51. 51. Kuperman D, Schofield B, Wills-Karp M, Grusby MJ: Signal transducer and activator of transcription factor 6 (Stat6)-deficient mice are protected from antigen-induced airway hyperresponsiveness and mucus production. J Exp Med 187:939-948, 1998
52. 52. Kaplan MH, Wurster AL, Grusby MJ: A signal transducer and activator of transcription (Stat)4-independent pathway for the development of T helper type 1 cells. J Exp Med 188:1191-1196, 1998
53. 53. Marine J, Winoto A: The human enhancer-binding protein Gata3 binds to several T-cell receptor regulatory elements. Proc Natl Acad Sci USA 88:7284-7288, 1991
54. 54. Laverriere AC, MacNeill C, Mueller C, Poelmann RE, Burch JB, Evans T: GATA-4/5/6, a subfamily of three transcription factors transcribed in developing heart and gut. J Biol Chem 269:23177-23184, 1994
55. 55. Leonard M, Brice M, Engel JD, Papayannopoulou T: Dynamics of GATA transcription factor expression during erythroid differentiation. Blood 82:1071-1079, 1993
56. 56. Zon LI, Yamaguchi Y, Yee K, Albee EA, Kimura A, Bennett JC, Orkin SH, Ackerman SJ: Expression of mRNA for the GATA-binding proteins in human eosinophils and basophils: Potential role in gene transcription. Blood 81:3234 3241, 1993
57. 57. Evans T, Felsenfeld G: The erythroid-specific transcription faclor Eryf1: A new finger protein. Cell 58:877-885, 1989
58. 58. Tsai SF, Martin DI, Zon LI, DqAndrea AD, Wong GG, Orkin SH: Cloning of cDNA for the major DNA-binding protein of the erythroid lineage through expression in mammalian cells. Nature 339:446-451, 1989
59. 59. Martin DI, Orkin SH: Transcriptional activation and DNA binding by the erythroid factor GF-1/NF-E1/Eryf 1. Genes Dev 4:1886-1898, 1990
60. 60. Ito E, Toki T, Ishihara H, Ohtani H, Gu L, Yokoyama M, Engel JD, Yamamoto M: Erythroid transcription factor GATA-1 is abundantly transcribed in mouse testis. Nature 362:466-468, 1993
61. 61. Smith VM, Lee PP, Szychowski S, Winoto A: GATA-3 dominant negative mutant. Functional redundancy of the T cell receptor alpha and beta enhancers. J Biol Chem 270:1515-1520, 1995
62. 62. Pevny L, Simon MC, Robertson E, Klein WH, Tsai SF, V DA, Orkin SH, Costantini F: Erythroid differentiation in chimaeric mice blocked by a targeted mutation in the gene for transcription factor GATA-1. Nature 349:257-260, 1991
63. 63. Yamamoto M, Ko LJ, Leonard MW, Beug H, Orkin SH, Engel JD: Activity and tissue-specific expression of the transcription factor NF-E1 multigene family. Genes Dev 4:1650-1662, 1990
64. 64. Lee ME, Temizer DH, Clifford JA. Quertermous T: Cloning of the GATA-binding protein that regulates endothelin-1 gene expression in endothelial cells. J Biol Chem 266:16188-16192, 1991
65. 65. Gill LL, Zaninetta D, Karjalainen K: A transcriptional enhancer of the mouse T cell receptor delta gene locus. Eur J Immunol 21:807-810, 1991
66. 66. Ho IC, Vorhees P, Marin N, Oakley BK, Tsai SF, Orkin SH, Leiden JM: Human GATA-3: A lineage-restricted transcription factor that regulates the expression of the T cell receptor alpha gene. EMBO J 10:1187-1192, 1991
67. 67. Joulin V, Bories D, Eleouet JF, Labastie MC, Chretien S, Mattei MG, Romeo PH: A T-cell specific TCR delta DNA binding protein is a member of the human GATA family. EMBO J 10:1809-1816, 1991
68. 68. Ko LJ, Yamamoto M, Leonard MW, George KM, Ting P, Engel JD: Murine and human T-lymphocyte GATA-3 factors mediate transcription through a cis-regulatory element within the human T-cell receptor delta gene enhancer. Mol Cell Biol 11:2778-2784, 1991
69. 69. Hambor JE, Mennone J, Coon ME, Hanke JH, Kavathas P: Identification and characterisation of an Alu-containing, T-cell-specific enhancer located in the last intron of the human CD8 alpha gene. Mol Cell Biol 13:7056-7070, 1993
70. 70. Landry DB, Engel JD, Sen R: Functional GATA-3 binding sites within murine CD8 alpha upstream regulatory sequences. J Exp Med 178:941-949, 1993
71. 71. Wurster AL, Siu G, Leiden JM, Hedrick SM: Elf-1 binds to a critical element in a second CD4 enhancer. Mol Cell Biol 14:6452-6463, 1994
72. 72. Penix L, Weaver WM, Pang Y, Young HA, Wilson CB: Two essential regulatory elements in the human interferon gamma promoter confer activation specific expression in T cells. J Exp Med 178:1483-1496, 1993
73. 73. Pandolfi PP, Roth ME, Karis A, Leonard MW, Dzierzak E, Grosveld FG, Engel JD, Lindenbaum MH: Targeted disruption of the GATA3 gene causes severe abnormalities in the nervous system and in fetal liver haematopoiesis. Nat Genet 11:40 44, 1995
74. 74. Ting CN, Olson MC, Barton KP, Leiden JM: Transcription factor GATA-3 is required for development of the T-cell lineage. Nature 384:474-478, 1996
75. 75. Zhang DH, Cohn L, Ray P, Bottomly K, Ray A: Transcription factor GATA-3 is differentially expressed in murine Th1 and Th2 cells and controls Th2-specific expression of the interleukin-5 gene. J Biol Chem 272:21597-21603, 1997
76. 76. Zheng W, Flavell RA: The transcription factor GATA-3 is necessary and sufficient for Th2 cytokine gene expression in CD4 T cells. Cell 89:587-596, 1997
77. 77. Ouyang W, Ranganath SH, Weindel K, Bhattacharya D, Murphy TL, Sha WC, Murphy KM: Inhibition of Th1 development mediated by GATA-3 through an IL-4-independent mechanism. Immunity 9:745-755, 1998
78. 78. Ho IC, Hodge MR, Rooney JW, Glimcher LH: The protooncogenc c-maf is responsible for tissue-specific expression of interleukin-4. Cell 85:973-983, 1996
79. 79. Hodge MR, Chun HJ, Rengarajan J, Alt A, Lieberson R, Glimcher LH: NF-AT-driven interleukin-4 transcription potentiated by NIP45. Science 274:1903-1905, 1996
80. 80. Ho IC, Lo D, Glimcher LH: c-maf promotes T helper cell type 2 (Th2) and attenuates Th1 differentiation by both interleukin 4-dependent and -independent mechanisms. J Exp Med 188: 1859-1866, 1998
81. 81. Ye BH. Lista F, Lo Coco F, Knowles DM, Offit K, Chaganti RS, Dalla-Favera R: Alterations of a zinc finger-encoding gene, BCL-6, in diffuse large-cell lymphoma. Science 262:747-750, 1993
82. 82. Migliazza A, Martinotti S, Chen W, Fusco C, Ye BH, Knowles DM, Offit K, Chaganti RS, Dalla-Favera R: Frequent somatic hypermutation of the 5′ noncoding region of the BCL6 gene in B-cell lymphoma. Proc Natl Acad Sci USA 92:12520-12524, 1995
83. 83. Chang CC, Ye BH, Chaganti RS, Dalla-Favera R: BCL-6, a POZ/zinc-finger protein, is a sequence-specific transcriptional repressor. Proc Natl Acad Sci USA 93:6947-6952, 1996
84. 84. Seyfert VL, Allman D, He Y, Staudt LM: Transcriptional repression by the proto-oncogene BCL-6. Oncogene 12:2331-2342, 1996
85. 85. Onizuka T, Moriyama M, Yamochi T, Kuroda T, Kazama A, Kanazawa N, Sato K, Kato T, Ota H, Mori S: BCL-6 gene product, a 92- to 98-kD nuclear phosphoprotein, is highly expressed in germinal center B cells and their neoplastic counterparts. Blood 86:28-37, 1995
86. 86. Allman D, Jain A, Dent A, Maile RR, Selvaggi T, Kehry MR, Staudt LM: BCL-6 expression during B-cell activation. Blood 87:5257-5268, 1996
87. 87. Dent AL, Shaffer AL, Yu X, Allman D, Staudt LM: Control of inflammation, cytokine expression, and germinal center formation by BCL-6. Science 276:589-592, 1997
88. 88. Crabtree GR, Clipstone NA: Signal transmission between the plasma membrane and nucleus of T lymphocytes. Annu Rev Biochem 63:1045-1083, 1994
89. 89. Rao A, Luo C, Hogan PG: Transcription factors of the NFAT family: Regulation and function. Annu Rev Immunol 15:707-747, 1997
90. 90. Cockerill GW, Bert AG, Ryan GR, Gamble JR, Vadas MA, Cockerill PN: Regulation of granulocyte-macrophagc colony-stimulating factor and E-selectin expression in endothelial cells by cyclosporin A and the T-cell transcription factor NFAT. Blood 86:2689 2698, 1995
91. 91. Molkentin JD, Lu JR, Antos CL, Markham B, Richardson J, Robbins J, Grant SR, Olson EN: A calcineurin-dependent transcriptional pathway for cardiac hypertrophy. Cell 93:215-228, 1998
92. 92. Schubert LA, King G, Cron RQ, Lewis DB, Aruffo A, Hollenbaugh D: The human gp39 promoter. Two distinct nuclear factors of activated T cell protein-binding elements contribute independently to transcriptional activation. J Biol Chem 270:29624-29627, 1995
93. 93. Tsytsykova AV, Tsitsikov EN, Geha RS: The CD40L promoter contains nuclear factor of activated T cells-binding motifs which require AP-1 binding for activation of transcription. J Biol Chem 271:3763-3770, 1996
94. 94. Perkins AS, Kim JH: Zinc fingers 1-7 of EVII fail to bind to the GATA motif by itself but require the core site GACAAGATA for binding. J Biol Chem 271:1104-1110, 1996
95. 95. Latinis KM, Norian LA, Eliason SL, Koretzky GA: Two NFAT transcription factor binding sites participate in the regulation of CD95 (Fas) ligand expression in activated human T cells. J Biol Chem 272:31427-31434, 1997
96. 96. Holtz-Heppelmann CJ, Algeciras A, Badley AD, Paya CV: Transcriptional regulation of the human FasL promoter-enhancer region. J Biol Chem 273:4416-4423, 1998
97. 97. Shaw KT, Ho AM, Raghavan A, Kim J, Jain J, Park J, Sharma S, Rao A, Hogan PG: Immunosuppressive drugs prevent a rapid dephosphorylation of transcription factor NFAT1 in stimulated immune cells. Proc Natl Acad Sci USA 92:11205-11209, 1995
98. 98. Lyakh L, Ghosh P, Rice NR: Expression of NFAT-family proteins in normal human T cells. Mol Cell Biol 17:2475-2484, 1997
99. 2+ response amplitude and duration. Nature 386:855-858, 1997
100. 100. Healy JI, Dolmetsch RE, Timmerman LA, Cyster JG, Thomas ML, Crabtree GR, Lewis RS, Goodnow CC: Different nuclear signals are activated hy the B cell receptor during positive versus negative signaling. Immunity 6:419-428, 1997
101. 101. Masuda ES, Naito Y, Tokumitsu H, Campbell D, Saito F, Hannum C, Arai K, Arai N: NFATx, a novel member of the nuclear factor of activated T cells family that is expressed predominantly in the thymus. Mol Cell Biol 15:2697 2706, 1995
102. 102. Amasaki Y, Masuda ES, Imamura R, Arai K, Arai N: Distinct NFAT family proteins arc involved in the nuclear NFAT-DNA binding complexes from human thymocyte subsets. J Immunol 160:2324-2333, 1998
103. 103. Hoey T, Sun YL, Williamson K, Xu X: Isolation of two new members of the NF-AT gene family and functional characterization of the NF-AT proteins. Immunity 2:461-472, 1995
104. 104. Loh C, Shaw KT, Carew J, Viola JP, Luo C, Perrino BA, Rao A: Calcineurin binds the transcription factor NFAT1 and reversibly regulates its activity. J Biol Chem 271:10884-10891, 1996
105. 105. Luo C, Shaw KT, Raghavan A, Aramburu J, Garcia-Cozar F, Perrino BA, Hogan PG, Rao A: Interaction of calcineurin with a domain of the transcription factor NFAT1 that controls nuclear import. Proc Natl Acad Sci USA 93:8907-8912, 1996
106. 106. Shibasaki F, Price ER, Milan D, McKeon F: Role of kinases and the phosphatase calcineurin in the nuclear shuttling of transcription factor NF-AT4. Nature 382:370-373, 1996
107. 107. Timmerman LA, Clipstone NA, Ho SN, Northrop JP, Crabtree GR: Rapid shuttling of NF-AT in discrimination of Ca2+ signals and immunosuppression. Nature 383:837-840, 1996
108. 108. Beals CR, Clipstone NA, Ho SN, Crabtree GR: Nuclear localization of NF-ATc by a calcineurin-dependent, cyclosporin-sensitive intramolecular interaction. Genes Dev 11:824-834, 1997
109. 109. Aramburu J, Garcia-Cozar F, Raghavan A, Okamura H, Rao A, Hogan PG: Selective inhibition of NFAT activation by a peptide spanning the calcineurin targeting site of NFAT. Mol Cell 1:627-637, 1998
110. 110. Jain J, McCaffrey PG, Miner Z, Kerppola TK, Lambert JN, Verdine GL, Curran T, Rao A: The T-cell transcription factor NFATp is a substrate for calcineurin and interacts with Fos and Jun. Nature 365:352-355, 1993
111. 111. Chen L, Glover JN, Hogan PG, Rao A, Harrison SC: Structure of the DNA-binding domains from NFAT, Fos and Jun bound specifically to DNA. Nature 392:42-48, 1998
112. 112. Rooney JW, Hodge MR, McCaffrey PG, Rao A, Glimcher LH: A common factor regulates both Th1-and Th2-specific cytokine gene expression. EMBO J 13:861-870, 1994
113. 113. Rooney JW, Hoey T, Glimcher LH: Coordinate and cooperative roles for NF-AT and AP-1 in the regulation of the murine IL-4 gene. Immunity 2:473-483, 1995
114. 114. Rincon M, Flavell RA: Regulation of the activity of the transcription factors AP-1 and NFAT during differentiation of precursor CD4+ T-cells into effector cells. Biochem Soc Trans 25:347-354, 1997
115. 115. Rincon M, Flavell RA: Transcription mediated by NFAT is highly inducible in effector CD4+ T helper 2 (Th2) cells but not in Th1 cells. Mol Cell Biol 17:1522-1534, 1997
116. 116. Hodge MR, Ranger AM, Charles de la Brousse F, Hoey T, Grusby MJ, Glimcher LH: Hyperproliferation and dysregulation of IL-4 expression in NF-ATp-deficient mice. Immunity 4:397-405, 1996
117. 117. Xanthoudakis S, Viola JP, Shaw KT, Luo C, Wallace JD, Bozza PT, Luk DC, Curran T, Rao A: An enhanced immune response in mice lacking the transcription factor NFAT1. Science 272:892-895, 1996
118. 118. Viola JP, Kiani A, Bozza PT, Rao A: Regulation of allergic inflammation and eosinophil recruitment in mice lacking the transcription factor NFAT1: Role of interleukin-4 (IL-4) and IL-5. Blood 91:2223-2230, 1998
119. 119. Kiani A, Viola JP, Lichtman AH, Rao A: Down-regulation of IL-4 gene transcription and control of Th2 cell differentiation by a mechanism involving NFAT1. Immunity 7:849-860, 1997
120. 120. de la Pompa JL, Timmerman LA, Takimoto H, Yoshida H, Elia AJ, Samper E, Potter J, Wakeham A, Marengere L, Langille BL, Crabtree GR, Mak TW: Role of the NF-ATc transcription factor in morphogenesis of cardiac valves and septum [see Comments]. Nature 392:182 186, 1998
121. 121. Ranger AM, Grusby MJ, Hodge MR, Gravallese EM, de la Brousse FC, Hoey T, Mickanin C, Baldwin HS, Glimcher LH: The transcription factor NF-ATc is essential for cardiac valve formation. Nature 392:186-190, 1998
122. 122. Ranger AM, Hodge MR, Gravallese EM, Oukka M, Davidson L, Alt FW, de la Brousse FC, Hoey T, Grusby M, Glimcher LH: Delayed lymphoid repopulation with defects in IL-4-driven responses produced by inactivation of NF-ATc. Immunity 8:125-134, 1998
123. 123. Yoshida H, Nishina H, Takimoto H, Marengere LE, Wakeham AC, Bouchard D, Kong YY, Ohteki T, Shahinian A, Bachmann M, Ohashi PS, Penninger JM, Crabtree GR, Mak TW: The transcription factor NF-ATc1 regulates lymphocyte proliferation and Th2 cytokine production. Immunity 8:115-124, 1998
124. 124. Oukka M, Ho IC, de la Brousse FC, Hoey T, Grusby MJ, Glimcher LH: The transcription factor NFAT4 is involved in the generation and survival of T cells. Immunity 9:295-304, 1998
125. 125. Ranger AM, Oukka M, Rengarajan J, Glimcher LH: Inhibitory function of two NFAT family members in lymphoid homeostasis and Th2 development. Immunity 9:627-635, 1998
126. 126. Jain J, Loh C, Rao A: Transcriptional regulation of the IL-2 gene. Curr Opin Immunol 7:333-342, 1995
127. 127. Serfling E, Avots A, Neumann M: The architecture of the interleukin-2 promoter: A reflection of T lymphocyte activation. Biochim Biophys Acta 1263:181-200, 1995
128. 128. Hanks M, Wurst W, Anson-Cartwright L, Auerbach AB, Joyner AL: Rescue of the En-1 mutant phenotype by replacement of En-1 with En-2. Science 269:679-682, 1995
129. 129. Wang Y, Schnegelsberg PN, Dausman J, Jaenisch R: Functional redundancy of the muscle-specific transcription factors Myf5 and myogenin. Nature 379:823-825, 1996