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研究生:余永倫
研究生(外文):Yu Yung-Luen
論文名稱:第三介白質依賴性存活反應中轉錄因子角色之探討
論文名稱(外文):Identification and characterization of transcriptional factors involved in IL-3-dependent survival responses
指導教授:嚴仲陽
指導教授(外文):Yen Jong-Young
學位類別:博士
校院名稱:國防醫學院
系所名稱:生命科學研究所
學門:生命科學學門
學類:生物學類
論文種類:學術論文
論文出版年:2002
畢業學年度:90
語文別:英文
論文頁數:148
中文關鍵詞:第三介白質細胞凋亡轉錄因子
外文關鍵詞:IL-3apoptosistranscriptional factor
相關次數:
  • 被引用被引用:0
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  • 下載下載:21
  • 收藏至我的研究室書目清單書目收藏:1
在造血系統中,細胞激素負責傳遞細胞增生,分化與存活的訊息。在那麼多種細胞激素中,其中第三介白質(IL-3)它對於前趨細胞和成熟血球細胞的存活效應扮演著重要的角色。雖然經過數十年的研究,第三介白質存活反應的訊息傳遞途徑與調控機制仍然尚未完全了解。所以在我的論文研究中,我將利用老鼠的第三介白質依賴性前趨B細胞株(Ba/F3)為我的研究模式系統,進一步來探討轉錄因子在存活反應中所扮演的角色。首先,在論文的第一部分,我試著想要找出哺乳動物中能與CES-2/E2A-HLF結合序列(CBE)結合且參與調控細胞凋亡(apoptosis)的結合蛋白。結果我發現CBE的結合體存在於許多哺乳動物的細胞株與組織中,且鑑定出CREB蛋白存在於其中一個主要的CBE結合體中。接著,我再利用能誘導表現且干擾CREB結合能力的突變蛋白(CREB-R287L)來進行研究,研究發現它確實能降低細胞的存活能力。進一步我也找到了抗細胞凋亡基因 Bcl-2上也具有此CBE結合體,所以認為它是其抗細胞凋亡目標基因之一。在我論文的第二部分,我主要研究另一個CBE結合蛋白E4BP4其轉錄的調控機制。E4BP4是一個含有bZIP轉錄因子家族的一員,它能受到第三介白質的調控且在第三介白質存活反應中扮演一個重要的角色。根據實驗指出,第三介白質活化E4bp4基因主要是透過轉錄層次。再經由啟動子分析,我找到在主要轉錄起始點後面有一個GATA結合序列為E4bp4基因表達所需。進一步也發現GATA轉錄因子家族中的GATA-1和GATA-2在活化E4bp4基因上扮演重要的角色,且參與第三介白質存活反應的訊息傳遞。論文的最後,我想要了解第三介白質是透過什麼樣的訊息傳遞途徑來活化E4bp4基因。研究指出,第三介白質能調控E4bp4啟動子上GATA結合序列結合的能力與GATA-1蛋白的磷酸化。接著我也發現第三介白質是透過RAF-MEK-MAPK這條訊息傳遞途徑來調控GATA-1的磷酸化,結合能力與E4bp4基因的表達,若進一步抑制MAPK就能降低E4bp4啟動子的活性與訊息RNA的表達。總之,根據以上我的論文研究指出,有許多轉錄因子能負責傳遞第三介白質的存活訊息且它們的表達與功能在第三介白質存活反應上扮演一個重要的角色。所以在血球細胞細胞凋亡的途徑中,發現GATA轉錄因子在E4bp4上所扮演的角色給我們很大的啟示,且對於未來了解造血過程與血球增生上更提供了另一個思考的方向。

Cytokines transduce signals of proliferation, differentiation, and survival in the hematopoietic system. As one of the most characterized cytokines, interleukin-3 (IL-3) is well known for its survival effect on both progenitors and mature blood cells. Although with the extensive studies in the past decades, the signaling pathways and regulatory mechanism of survival response of IL-3 still is not completely understood. In my thesis, I will use a murine IL-3-dependent pro-B cell line, Ba/F3, as a model system to explore the role of transcriptional factors in survival responses. The first part of my thesis was aiming to identify the mammalian CES-2/E2A-HLF Binding Element (CBE)-binding proteins that may be involved in apoptosis regulation. I was able to demonstrate the existence of multiple binding complexes of CBE in various mammalian cell lines and tissues and identify cyclic AMP (cAMP)-responsive element (CRE)-binding protein (CREB) as the component of one major CBE complex. By conditionally expressing CREB-R287L mutant, which interferes the binding ability of wild-type CREB, I demonstrated that the viability of cell lines was reduced in the presence of mutant CREB. Moreover, my data also suggested the Bcl-2 gene as one candidate cellular target of the CREB-containing CBE complex. In the second part of my thesis, the transcriptional regulatory mechanism of another CBE-binding protein, E4BP4, is studied. E4bp4, a member of the basic region-leucine zipper (bZIP) transcriptional factor superfamily, is up-regulated by the IL-3 and plays an important role in IL-3’s antiapoptotic response. In this study, I have demonstrated that IL-3 activation of the E4bp4 gene is regulated at the transcriptional level. Through promoter analysis, I showed that a GATA motif downstream of the transcriptional initiation site is essential for E4bp4 expression in the Ba/F3 cells. I also demonstrated that GATA-binding factors, most likely GATA-1 and GATA-2, play an important role in the transcriptional activation of E4bp4, and are involved in the antiapoptotic signaling of IL-3. The third part of my thesis is devoted to investigate the signaling pathway responsible for induction of the survival gene E4bp4 by IL-3 in Ba/F3 cells. In this study, I demonstrated that both the GATA site binding ability and phosphorylation of the GATA-1 protein are regulated by IL-3. Furthermore, I demonstrated that the RAF-MEK-MAPK signaling pathway mediates the IL-3-induced phosphorylation and binding activity of GATA-1, and inhibition of MAPK leads to decrease the promoter activity and reduce the expression of the endogenous mRNA of E4bp4. In summary, the works in my dissertation clearly demonstrated that there are some transcriptional factors involved in transducing survival signal of IL-3 and their expression and function are both critical to IL-3’s survival responses. Furthermore, the discovery of GATA factors functioning in the upstream of the E4bp4 gene may extend our knowledge on the apoptotic pathway in hematopoietic cells, and may contribute to our further understanding of the processes of hematopoiesis and leukemogenesis.

Contents I
List of Figures III
List of Tables V
List of Abbreviation VI
Chinese Summary VIII
English Summary X
Chapter I: General Introduction 1
Chapter II: CREB is one component of the binding complex of the CES-2/E2A-HLF
binding element and is an integral part of the interleukin-3 survival signal 23
Abstract 24
Introduction 25
Materials and Methods 28
Results 33
Discussion 38
Figures 41
Chapter III: GATA factors are essential for transcription of the survival gene E4bp4 and
the viability response of interleukin-3 in Ba/F3 hematopoietic cells 50
Abstract 51
Introduction 52
Materials and Methods 54
Results 66
Discussion 76
Figures 80
Chapter IV: The RAF-MEK-MAPK signaling pathway mediates interleukin-3-dependent
E4bp4 expression and the function of GATA-1 93
Abstract 94
Introduction 95
Materials and Methods 98
Results 103
Discussion 108
Figures 111
Chapter V: General Discussion 117
References 124
Appendixes

1. Aggarwal BB, Puri R: Human cytokines : their role in disease and therapy. Boston: Blackwell Scientific Publications; 1994.
2. Mizel SB: The interleukins. Faseb J 1989, 3:2379-2388.
3. Schrader JW: The panspecific hemopoietin of activated T lymphocytes (interleukin-3). Annu Rev Immunol 1986, 4:205-230.
4. Ihle JN, Keller J, Oroszlan S, Henderson LE, Copeland TD, Fitch F, Prystowsky MB, Goldwasser E, Schrader JW, Palaszynski E, et al.: Biologic properties of homogeneous interleukin 3. I. Demonstration of WEHI-3 growth factor activity, mast cell growth factor activity, p cell-stimulating factor activity, colony-stimulating factor activity, and histamine-producing cell-stimulating factor activity. J Immunol 1983, 131:282-287.
5. Mire-Sluis AR, Thorpe R: Cytokines. San Diego: Academic Press; 1998.
6. Mui AL, Wakao H, Kinoshita T, Kitamura T, Miyajima A: Suppression of interleukin-3-induced gene expression by a C-terminal truncated Stat5: role of Stat5 in proliferation. Embo J 1996, 15:2425-2433.
7. Wang D, Stravopodis D, Teglund S, Kitazawa J, Ihle JN: Naturally occurring dominant negative variants of Stat5. Mol Cell Biol 1996, 16:6141-6148.
8. Yoshimura A, Ichihara M, Kinjyo I, Moriyama M, Copeland NG, Gilbert DJ, Jenkins NA, Hara T, Miyajima A: Mouse oncostatin M: an immediate early gene induced by multiple cytokines through the JAK-STAT5 pathway. Embo J 1996, 15:1055-1063.
9. Okuda K, Sanghera JS, Pelech SL, Kanakura Y, Hallek M, Griffin JD, Druker BJ: Granulocyte-macrophage colony-stimulating factor, interleukin-3, and steel factor induce rapid tyrosine phosphorylation of p42 and p44 MAP kinase. Blood 1992, 79:2880-2887.
10. Satoh T, Nakafuku M, Miyajima A, Kaziro Y: Involvement of ras p21 protein in signal-transduction pathways from interleukin 2, interleukin 3, and granulocyte/macrophage colony-stimulating factor, but not from interleukin 4. Proc Natl Acad Sci U S A 1991, 88:3314-3318.
11. Carroll MP, Clark-Lewis I, Rapp UR, May WS: Interleukin-3 and granulocyte-macrophage colony-stimulating factor mediate rapid phosphorylation and activation of cytosolic c-raf. J Biol Chem 1990, 265:19812-19817.
12. Kanakura Y, Druker B, Wood KW, Mamon HJ, Okuda K, Roberts TM, Griffin JD: Granulocyte-macrophage colony-stimulating factor and interleukin-3 induce rapid phosphorylation and activation of the proto-oncogene Raf-1 in a human factor-dependent myeloid cell line. Blood 1991, 77:243-248.
13. Okuda K, Ernst TJ, Griffin JD: Inhibition of p21ras activation blocks proliferation but not differentiation of interleukin-3-dependent myeloid cells. J Biol Chem 1994, 269:24602-24607.
14. Nagata Y, Moriguchi T, Nishida E, Todokoro K: Activation of p38 MAP kinase pathway by erythropoietin and interleukin-3. Blood 1997, 90:929-934.
15. Terada K, Kaziro Y, Satoh T: Ras-dependent activation of c-Jun N-terminal kinase/stress-activated protein kinase in response to interleukin-3 stimulation in hematopoietic BaF3 cells. J Biol Chem 1997, 272:4544-4548.
16. Nagata Y, Nishida E, Todokoro K: Activation of JNK signaling pathway by erythropoietin, thrombopoietin, and interleukin-3. Blood 1997, 89:2664-2669.
17. Smith A, Ramos-Morales F, Ashworth A, Collins M: A role for JNK/SAPK in proliferation, but not apoptosis, of IL-3-dependent cells. Curr Biol 1997, 7:893-896.
18. Gold MR, Duronio V, Saxena SP, Schrader JW, Aebersold R: Multiple cytokines activate phosphatidylinositol 3-kinase in hemopoietic cells. Association of the enzyme with various tyrosine-phosphorylated proteins. J Biol Chem 1994, 269:5403-5412.
19. Songyang Z, Baltimore D, Cantley LC, Kaplan DR, Franke TF: Interleukin 3-dependent survival by the Akt protein kinase. Proc Natl Acad Sci U S A 1997, 94:11345-11350.
20. Calvo V, Wood M, Gjertson C, Vik T, Bierer BE: Activation of 70-kDa S6 kinase, induced by the cytokines interleukin-3 and erythropoietin and inhibited by rapamycin, is not an absolute requirement for cell proliferation. Eur J Immunol 1994, 24:2664-2671.
21. Brandt JE, Bhalla K, Hoffman R: Effects of interleukin-3 and c-kit ligand on the survival of various classes of human hematopoietic progenitor cells. Blood 1994, 83:1507-1514.
22. Kinoshita T, Yokota T, Arai K, Miyajima A: Suppression of apoptotic death in hematopoietic cells by signalling through the IL-3/GM-CSF receptors. Embo J 1995, 14:266-275.
23. Nicola NA, Robb L, Metcalf D, Cary D, Drinkwater CC, Begley CG: Functional inactivation in mice of the gene for the interleukin-3 (IL-3)-specific receptor beta-chain: implications for IL-3 function and the mechanism of receptor transmodulation in hematopoietic cells. Blood 1996, 87:2665-2674.
24. Terada K, Kaziro Y, Satoh T: Ras is not required for the interleukin 3-induced proliferation of a mouse pro-B cell line, BaF3. J Biol Chem 1995, 270:27880-27886.
25. Cleveland JL, Troppmair J, Packham G, Askew DS, Lloyd P, Gonzalez-Garcia M, Nunez G, Ihle JN, Rapp UR: v-raf suppresses apoptosis and promotes growth of interleukin-3-dependent myeloid cells. Oncogene 1994, 9:2217-2226.
26. Kinoshita T, Shirouzu M, Kamiya A, Hashimoto K, Yokoyama S, Miyajima A: Raf/MAPK and rapamycin-sensitive pathways mediate the anti-apoptotic function of p21Ras in IL-3-dependent hematopoietic cells. Oncogene 1997, 15:619-627.
27. Perkins GR, Marshall CJ, Collins MK: The role of MAP kinase kinase in interleukin-3 stimulation of proliferation. Blood 1996, 87:3669-3675.
28. Garland JM, Rudin C: Cytochrome c induces caspase-dependent apoptosis in intact hematopoietic cells and overrides apoptosis suppression mediated by bcl-2, growth factor signaling, MAP-kinase-kinase, and malignant change. Blood 1998, 92:1235-1246.
29. Poommipanit PB, Chen B, Oltvai ZN: Interleukin-3 induces the phosphorylation of a distinct fraction of bcl-2. J Biol Chem 1999, 274:1033-1039.
30. Dumon S, Santos SC, Debierre-Grockiego F, Gouilleux-Gruart V, Cocault L, Boucheron C, Mollat P, Gisselbrecht S, Gouilleux F: IL-3 dependent regulation of Bcl-xL gene expression by STAT5 in a bone marrow derived cell line. Oncogene 1999, 18:4191-4199.
31. Gesbert F, Griffin JD: Bcr/Abl activates transcription of the Bcl-X gene through STAT5. Blood 2000, 96:2269-2276.
32. Wang JM, Chao JR, Chen W, Kuo ML, Yen JJ, Yang-Yen HF: The antiapoptotic gene mcl-1 is up-regulated by the phosphatidylinositol 3-kinase/Akt signaling pathway through a transcription factor complex containing CREB. Mol Cell Biol 1999, 19:6195-6206.
33. Leverrier Y, Thomas J, Perkins GR, Mangeney M, Collins MK, Marvel J: In bone marrow derived Baf-3 cells, inhibition of apoptosis by IL-3 is mediated by two independent pathways. Oncogene 1997, 14:425-430.
34. Rinaudo MS, Su K, Falk LA, Halder S, Mufson RA: Human interleukin-3 receptor modulates bcl-2 mRNA and protein levels through protein kinase C in TF-1 cells. Blood 1995, 86:80-88.
35. Kinoshita T, Yokota T, Arai K, Miyajima A: Regulation of Bcl-2 expression by oncogenic Ras protein in hematopoietic cells. Oncogene 1995, 10:2207-2212.
36. Lin EY, Orlofsky A, Wang HG, Reed JC, Prystowsky MB: A1, a Bcl-2 family member, prolongs cell survival and permits myeloid differentiation. Blood 1996, 87:983-992.
37. Baffy G, Miyashita T, Williamson JR, Reed JC: Apoptosis induced by withdrawal of interleukin-3 (IL-3) from an IL-3-dependent hematopoietic cell line is associated with repartitioning of intracellular calcium and is blocked by enforced Bcl-2 oncoprotein production. J Biol Chem 1993, 268:6511-6519.
38. Ito T, Deng X, Carr B, May WS: Bcl-2 phosphorylation required for anti-apoptosis function. J Biol Chem 1997, 272:11671-11673.
39. Gotoh N, Tojo A, Shibuya M: A novel pathway from phosphorylation of tyrosine residues 239/240 of Shc, contributing to suppress apoptosis by IL-3. Embo J 1996, 15:6197-6204.
40. Suzuki J, Kaziro Y, Koide H: An activated mutant of R-Ras inhibits cell death caused by cytokine deprivation in BaF3 cells in the presence of IGF-I. Oncogene 1997, 15:1689-1697.
41. Marte BM, Rodriguez-Viciana P, Wennstrom S, Warne PH, Downward J: R-Ras can activate the phosphoinositide 3-kinase but not the MAP kinase arm of the Ras effector pathways. Curr Biol 1997, 7:63-70.
42. Scheid MP, Lauener RW, Duronio V: Role of phosphatidylinositol 3-OH-kinase activity in the inhibition of apoptosis in haemopoietic cells: phosphatidylinositol 3-OH-kinase inhibitors reveal a difference in signalling between interleukin-3 and granulocyte-macrophage colony stimulating factor. Biochem J 1995, 312 ( Pt 1):159-162.
43. Marte BM, Downward J: PKB/Akt: connecting phosphoinositide 3-kinase to cell survival and beyond. Trends Biochem Sci 1997, 22:355-358.
44. Datta SR, Dudek H, Tao X, Masters S, Fu H, Gotoh Y, Greenberg ME: Akt phosphorylation of BAD couples survival signals to the cell-intrinsic death machinery. Cell 1997, 91:231-241.
45. Kerr JF, Wyllie AH, Currie AR: Apoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics. Br J Cancer 1972, 26:239-257.
46. Sulston JE, Horvitz HR: Post-embryonic cell lineages of the nematode, Caenorhabditis elegans. Dev Biol 1977, 56:110-156.
47. Ellis RE, Yuan JY, Horvitz HR: Mechanisms and functions of cell death. Annu Rev Cell Biol 1991, 7:663-698.
48. Hengartner MO, Horvitz HR: Programmed cell death in Caenorhabditis elegans. Curr Opin Genet Dev 1994, 4:581-586.
49. Hengartner MO: Genetic control of programmed cell death and aging in the nematode Caenorhabditis elegans. Exp Gerontol 1997, 32:363-374.
50. Liu QA, Hengartner MO: The molecular mechanism of programmed cell death in C. elegans. Ann N Y Acad Sci 1999, 887:92-104.
51. Meier P, Finch A, Evan G: Apoptosis in development. Nature 2000, 407:796-801.
52. Chinnaiyan AM, O'Rourke K, Lane BR, Dixit VM: Interaction of CED-4 with CED-3 and CED-9: a molecular framework for cell death. Science 1997, 275:1122-1126.
53. Chinnaiyan AM, Chaudhary D, O'Rourke K, Koonin EV, Dixit VM: Role of CED-4 in the activation of CED-3. Nature 1997, 388:728-729.
54. Spector MS, Desnoyers S, Hoeppner DJ, Hengartner MO: Interaction between the C. elegans cell-death regulators CED-9 and CED-4. Nature 1997, 385:653-656.
55. Wu D, Wallen HD, Nunez G: Interaction and regulation of subcellular localization of CED-4 by CED-9. Science 1997, 275:1126-1129.
56. Pan G, O'Rourke K, Dixit VM: Caspase-9, Bcl-XL, and Apaf-1 form a ternary complex. J Biol Chem 1998, 273:5841-5845.
57. Hu Y, Benedict MA, Wu D, Inohara N, Nunez G: Bcl-XL interacts with Apaf-1 and inhibits Apaf-1-dependent caspase-9 activation. Proc Natl Acad Sci U S A 1998, 95:4386-4391.
58. Conradt B, Horvitz HR: The C. elegans protein EGL-1 is required for programmed cell death and interacts with the Bcl-2-like protein CED-9. Cell 1998, 93:519-529.
59. Ellis RE, Horvitz HR: Two C. elegans genes control the programmed deaths of specific cells in the pharynx. Development 1991, 112:591-603.
60. Metzstein MM, Hengartner MO, Tsung N, Ellis RE, Horvitz HR: Transcriptional regulator of programmed cell death encoded by Caenorhabditis elegans gene ces-2. Nature 1996, 382:545-547.
61. Inukai T, Inoue A, Kurosawa H, Goi K, Shinjyo T, Ozawa K, Mao M, Inaba T, Look AT: SLUG, a ces-1-related zinc finger transcription factor gene with antiapoptotic activity, is a downstream target of the E2A-HLF oncoprotein. Mol Cell 1999, 4:343-352.
62. Hemavathy K, Guru SC, Harris J, Chen JD, Ip YT: Human Slug is a repressor that localizes to sites of active transcription. Mol Cell Biol 2000, 20:5087-5095.
63. Inaba T, Inukai T, Yoshihara T, Seyschab H, Ashmun RA, Canman CE, Laken SJ, Kastan MB, Look AT: Reversal of apoptosis by the leukaemia-associated E2A-HLF chimaeric transcription factor. Nature 1996, 382:541-544.
64. Metzstein MM, Horvitz HR: The C. elegans cell death specification gene ces-1 encodes a snail family zinc finger protein. Mol Cell 1999, 4:309-319.
65. Lindsten T, Ross AJ, King A, Zong WX, Rathmell JC, Shiels HA, Ulrich E, Waymire KG, Mahar P, Frauwirth K, et al.: The combined functions of proapoptotic Bcl-2 family members bak and bax are essential for normal development of multiple tissues. Mol Cell 2000, 6:1389-1399.
66. Montminy MR, Bilezikjian LM: Binding of a nuclear protein to the cyclic-AMP response element of the somatostatin gene. Nature 1987, 328:175-178.
67. Yamamoto KK, Gonzalez GA, Biggs WH, 3rd, Montminy MR: Phosphorylation-induced binding and transcriptional efficacy of nuclear factor CREB. Nature 1988, 334:494-498.
68. Klemm DJ, Roesler WJ, Boras T, Colton LA, Felder K, Reusch JE: Insulin stimulates cAMP-response element binding protein activity in HepG2 and 3T3-L1 cell lines. J Biol Chem 1998, 273:917-923.
69. Walker WH, Fucci L, Habener JF: Expression of the gene encoding transcription factor cyclic adenosine 3',5'-monophosphate (cAMP) response element-binding protein (CREB): regulation by follicle-stimulating hormone-induced cAMP signaling in primary rat Sertoli cells. Endocrinology 1995, 136:3534-3545.
70. Ghosh A, Greenberg ME: Distinct roles for bFGF and NT-3 in the regulation of cortical neurogenesis. Neuron 1995, 15:89-103.
71. Ginty DD, Bonni A, Greenberg ME: Nerve growth factor activates a Ras-dependent protein kinase that stimulates c-fos transcription via phosphorylation of CREB. Cell 1994, 77:713-725.
72. Tan Y, Rouse J, Zhang A, Cariati S, Cohen P, Comb MJ: FGF and stress regulate CREB and ATF-1 via a pathway involving p38 MAP kinase and MAPKAP kinase-2. Embo J 1996, 15:4629-4642.
73. Pende M, Fisher TL, Simpson PB, Russell JT, Blenis J, Gallo V: Neurotransmitter- and growth factor-induced cAMP response element binding protein phosphorylation in glial cell progenitors: role of calcium ions, protein kinase C, and mitogen-activated protein kinase/ribosomal S6 kinase pathway. J Neurosci 1997, 17:1291-1301.
74. Sheng M, Thompson MA, Greenberg ME: CREB: a Ca(2+)-regulated transcription factor phosphorylated by calmodulin-dependent kinases. Science 1991, 252:1427-1430.
75. Shaywitz AJ, Greenberg ME: CREB: a stimulus-induced transcription factor activated by a diverse array of extracellular signals. Annu Rev Biochem 1999, 68:821-861.
76. Gonzalez GA, Montminy MR: Cyclic AMP stimulates somatostatin gene transcription by phosphorylation of CREB at serine 133. Cell 1989, 59:675-680.
77. Beitner-Johnson D, Millhorn DE: Hypoxia induces phosphorylation of the cyclic AMP response element-binding protein by a novel signaling mechanism. J Biol Chem 1998, 273:19834-19839.
78. Bonni A, Brunet A, West AE, Datta SR, Takasu MA, Greenberg ME: Cell survival promoted by the Ras-MAPK signaling pathway by transcription-dependent and -independent mechanisms. Science 1999, 286:1358-1362.
79. Du K, Montminy M: CREB is a regulatory target for the protein kinase Akt/PKB. J Biol Chem 1998, 273:32377-32379.
80. Brindle P, Linke S, Montminy M: Protein-kinase-A-dependent activator in transcription factor CREB reveals new role for CREM repressors. Nature 1993, 364:821-824.
81. Gonzalez GA, Menzel P, Leonard J, Fischer WH, Montminy MR: Characterization of motifs which are critical for activity of the cyclic AMP-responsive transcription factor CREB. Mol Cell Biol 1991, 11:1306-1312.
82. Chrivia JC, Kwok RP, Lamb N, Hagiwara M, Montminy MR, Goodman RH: Phosphorylated CREB binds specifically to the nuclear protein CBP. Nature 1993, 365:855-859.
83. Kwok RP, Lundblad JR, Chrivia JC, Richards JP, Bachinger HP, Brennan RG, Roberts SG, Green MR, Goodman RH: Nuclear protein CBP is a coactivator for the transcription factor CREB. Nature 1994, 370:223-226.
84. Yano S, Tokumitsu H, Soderling TR: Calcium promotes cell survival through CaM-K kinase activation of the protein-kinase-B pathway. Nature 1998, 396:584-587.
85. Riccio A, Ahn S, Davenport CM, Blendy JA, Ginty DD: Mediation by a CREB family transcription factor of NGF-dependent survival of sympathetic neurons. Science 1999, 286:2358-2361.
86. Yang YM, Dolan LR, Ronai Z: Expression of dominant negative CREB reduces resistance to radiation of human melanoma cells. Oncogene 1996, 12:2223-2233.
87. Jean D, Harbison M, McConkey DJ, Ronai Z, Bar-Eli M: CREB and its associated proteins act as survival factors for human melanoma cells. J Biol Chem 1998, 273:24884-24890.
88. Barton K, Muthusamy N, Chanyangam M, Fischer C, Clendenin C, Leiden JM: Defective thymocyte proliferation and IL-2 production in transgenic mice expressing a dominant-negative form of CREB. Nature 1996, 379:81-85.
89. Bussfeld D, Bacher M, Moritz A, Gemsa D, Sprenger H: Expression of transcription factor genes after influenza A virus infection. Immunobiology 1997, 198:291-298.
90. Blendy JA, Kaestner KH, Weinbauer GF, Nieschlag E, Schutz G: Severe impairment of spermatogenesis in mice lacking the CREM gene. Nature 1996, 380:162-165.
91. Nantel F, Monaco L, Foulkes NS, Masquilier D, LeMeur M, Henriksen K, Dierich A, Parvinen M, Sassone-Corsi P: Spermiogenesis deficiency and germ-cell apoptosis in CREM-mutant mice. Nature 1996, 380:159-162.
92. Rudolph D, Tafuri A, Gass P, Hammerling GJ, Arnold B, Schutz G: Impaired fetal T cell development and perinatal lethality in mice lacking the cAMP response element binding protein. Proc Natl Acad Sci U S A 1998, 95:4481-4486.
93. Bleckmann SC, Blendy JA, Rudolph D, Monaghan AP, Schmid W, Schutz G: Activating transcription factor 1 and CREB are important for cell survival during early mouse development. Mol Cell Biol 2002, 22:1919-1925.
94. Lee HJ, Mignacca RC, Sakamoto KM: Transcriptional activation of egr-1 by granulocyte-macrophage colony-stimulating factor but not interleukin 3 requires phosphorylation of cAMP response element-binding protein (CREB) on serine 133. J Biol Chem 1995, 270:15979-15983.
95. Wilson BE, Mochon E, Boxer LM: Induction of bcl-2 expression by phosphorylated CREB proteins during B-cell activation and rescue from apoptosis. Mol Cell Biol 1996, 16:5546-5556.
96. Merry DE, Korsmeyer SJ: Bcl-2 gene family in the nervous system. Annu Rev Neurosci 1997, 20:245-267.
97. Ikushima S, Inukai T, Inaba T, Nimer SD, Cleveland JL, Look AT: Pivotal role for the NFIL3/E4BP4 transcription factor in interleukin 3-mediated survival of pro-B lymphocytes. Proc Natl Acad Sci U S A 1997, 94:2609-2614.
98. Inaba T, Roberts WM, Shapiro LH, Jolly KW, Raimondi SC, Smith SD, Look AT: Fusion of the leucine zipper gene HLF to the E2A gene in human acute B-lineage leukemia. Science 1992, 257:531-534.
99. Hunger SP, Ohyashiki K, Toyama K, Cleary ML: Hlf, a novel hepatic bZIP protein, shows altered DNA-binding properties following fusion to E2A in t(17;19) acute lymphoblastic leukemia. Genes Dev 1992, 6:1608-1620.
100. Hunger SP, Brown R, Cleary ML: DNA-binding and transcriptional regulatory properties of hepatic leukemia factor (HLF) and the t(17;19) acute lymphoblastic leukemia chimera E2A-HLF. Mol Cell Biol 1994, 14:5986-5996.
101. Inaba T, Shapiro LH, Funabiki T, Sinclair AE, Jones BG, Ashmun RA, Look AT: DNA-binding specificity and trans-activating potential of the leukemia-associated E2A-hepatic leukemia factor fusion protein. Mol Cell Biol 1994, 14:3403-3413.
102. Inukai T, Inaba T, Yoshihara T, Look AT: Cell transformation mediated by homodimeric E2A-HLF transcription factors. Mol Cell Biol 1997, 17:1417-1424.
103. Inukai T, Inaba T, Ikushima S, Look AT: The AD1 and AD2 transactivation domains of E2A are essential for the antiapoptotic activity of the chimeric oncoprotein E2A-HLF. Mol Cell Biol 1998, 18:6035-6043.
104. Cowell IG, Skinner A, Hurst HC: Transcriptional repression by a novel member of the bZIP family of transcription factors. Mol Cell Biol 1992, 12:3070-3077.
105. Zhang W, Zhang J, Kornuc M, Kwan K, Frank R, Nimer SD: Molecular cloning and characterization of NF-IL3A, a transcriptional activator of the human interleukin-3 promoter. Mol Cell Biol 1995, 15:6055-6063.
106. Chen WJ, Lewis KS, Chandra G, Cogswell JP, Stinnett SW, Kadwell SH, Gray JG: Characterization of human E4BP4, a phosphorylated bZIP factor. Biochim Biophys Acta 1995, 1264:388-396.
107. Lai CK, Ting LP: Transcriptional repression of human hepatitis B virus genes by a bZIP family member, E4BP4. J Virol 1999, 73:3197-3209.
108. Ishida H, Ueda K, Ohkawa K, Kanazawa Y, Hosui A, Nakanishi F, Mita E, Kasahara A, Sasaki Y, Hori M, et al.: Identification of multiple transcription factors, HLF, FTF, and E4BP4, controlling hepatitis B virus enhancer II. J Virol 2000, 74:1241-1251.
109. Doi M, Nakajima Y, Okano T, Fukada Y: Light-induced phase-delay of the chicken pineal circadian clock is associated with the induction of cE4bp4, a potential transcriptional repressor of cPer2 gene. Proc Natl Acad Sci U S A 2001, 98:8089-8094.
110. Cowell IG, Hurst HC: Transcriptional repression by the human bZIP factor E4BP4: definition of a minimal repression domain. Nucleic Acids Res 1994, 22:59-65.
111. Cowell IG, Hurst HC: Protein-protein interaction between the transcriptional repressor E4BP4 and the TBP-binding protein Dr1. Nucleic Acids Res 1996, 24:3607-3613.
112. Mueller CR, Maire P, Schibler U: DBP, a liver-enriched transcriptional activator, is expressed late in ontogeny and its tissue specificity is determined posttranscriptionally. Cell 1990, 61:279-291.
113. Drolet DW, Scully KM, Simmons DM, Wegner M, Chu KT, Swanson LW, Rosenfeld MG: TEF, a transcription factor expressed specifically in the anterior pituitary during embryogenesis, defines a new class of leucine zipper proteins. Genes Dev 1991, 5:1739-1753.
114. Kuribara R, Kinoshita T, Miyajima A, Shinjyo T, Yoshihara T, Inukai T, Ozawa K, Look AT, Inaba T: Two distinct interleukin-3-mediated signal pathways, Ras-NFIL3 (E4BP4) and Bcl-xL, regulate the survival of murine pro-B lymphocytes. Mol Cell Biol 1999, 19:2754-2762.
115. Chu CC, Paul WE: Expressed genes in interleukin-4 treated B cells identified by cDNA representational difference analysis. Mol Immunol 1998, 35:487-502.
116. Wallace AD, Wheeler TT, Young DA: Inducibility of E4BP4 suggests a novel mechanism of negative gene regulation by glucocorticoids. Biochem Biophys Res Commun 1997, 232:403-406.
117. Nishimura Y, Tanaka T: Calcium-dependent activation of nuclear factor regulated by interleukin 3/adenovirus E4 promoter-binding protein gene expression by calcineurin/nuclear factor of activated T cells and calcium/calmodulin-dependent protein kinase signaling. J Biol Chem 2001, 276:19921-19928.
118. Mitsui S, Yamaguchi S, Matsuo T, Ishida Y, Okamura H: Antagonistic role of E4BP4 and PAR proteins in the circadian oscillatory mechanism. Genes Dev 2001, 15:995-1006.
119. Merika M, Orkin SH: DNA-binding specificity of GATA family transcription factors. Mol Cell Biol 1993, 13:3999-4010.
120. Evans T, Reitman M, Felsenfeld G: An erythrocyte-specific DNA-binding factor recognizes a regulatory sequence common to all chicken globin genes. Proc Natl Acad Sci U S A 1988, 85:5976-5980.
121. Evans T, Felsenfeld G: The erythroid-specific transcription factor Eryf1: a new finger protein. Cell 1989, 58:877-885.
122. Tsai SF, Martin DI, Zon LI, D'Andrea AD, Wong GG, Orkin SH: Cloning of cDNA for the major DNA-binding protein of the erythroid lineage through expression in mammalian cells. Nature 1989, 339:446-451.
123. Trainor CD, Omichinski JG, Vandergon TL, Gronenborn AM, Clore GM, Felsenfeld G: A palindromic regulatory site within vertebrate GATA-1 promoters requires both zinc fingers of the GATA-1 DNA-binding domain for high-affinity interaction. Mol Cell Biol 1996, 16:2238-2247.
124. Weiss MJ, Yu C, Orkin SH: Erythroid-cell-specific properties of transcription factor GATA-1 revealed by phenotypic rescue of a gene-targeted cell line. Mol Cell Biol 1997, 17:1642-1651.
125. Weiss MJ, Orkin SH: GATA transcription factors: key regulators of hematopoiesis. Exp Hematol 1995, 23:99-107.
126. Shivdasani RA, Fujiwara Y, McDevitt MA, Orkin SH: A lineage-selective knockout establishes the critical role of transcription factor GATA-1 in megakaryocyte growth and platelet development. Embo J 1997, 16:3965-3973.
127. Orkin SH: GATA-binding transcription factors in hematopoietic cells. Blood 1992, 80:575-581.
128. Visvader J, Adams JM: Megakaryocytic differentiation induced in 416B myeloid cells by GATA-2 and GATA-3 transgenes or 5-azacytidine is tightly coupled to GATA-1 expression. Blood 1993, 82:1493-1501.
129. Kulessa H, Frampton J, Graf T: GATA-1 reprograms avian myelomonocytic cell lines into eosinophils, thromboblasts, and erythroblasts. Genes Dev 1995, 9:1250-1262.
130. Takahashi S, Komeno T, Suwabe N, Yoh K, Nakajima O, Nishimura S, Kuroha T, Nagasawa T, Yamamoto M: Role of GATA-1 in proliferation and differentiation of definitive erythroid and megakaryocytic cells in vivo. Blood 1998, 92:434-442.
131. Weiss MJ, Orkin SH: Transcription factor GATA-1 permits survival and maturation of erythroid precursors by preventing apoptosis. Proc Natl Acad Sci U S A 1995, 92:9623-9627.
132. Whyatt DJ, Karis A, Harkes IC, Verkerk A, Gillemans N, Elefanty AG, Vairo G, Ploemacher R, Grosveld F, Philipsen S: The level of the tissue-specific factor GATA-1 affects the cell-cycle machinery. Genes Funct 1997, 1:11-24.
133. Whyatt D, Lindeboom F, Karis A, Ferreira R, Milot E, Hendriks R, de Bruijn M, Langeveld A, Gribnau J, Grosveld F, et al.: An intrinsic but cell-nonautonomous defect in GATA-1-overexpressing mouse erythroid cells. Nature 2000, 406:519-524.
134. Orlic D, Anderson S, Biesecker LG, Sorrentino BP, Bodine DM: Pluripotent hematopoietic stem cells contain high levels of mRNA for c-kit, GATA-2, p45 NF-E2, and c-myb and low levels or no mRNA for c-fms and the receptors for granulocyte colony-stimulating factor and interleukins 5 and 7. Proc Natl Acad Sci U S A 1995, 92:4601-4605.
135. Ikonomi P, Rivera CE, Riordan M, Washington G, Schechter AN, Noguchi CT: Overexpression of GATA-2 inhibits erythroid and promotes megakaryocyte differentiation. Exp Hematol 2000, 28:1423-1431.
136. Onodera K, Yomogida K, Suwabe N, Takahashi S, Muraosa Y, Hayashi N, Ito E, Gu L, Rassoulzadegan M, Engel JD, et al.: Conserved structure, regulatory elements, and transcriptional regulation from the GATA-1 gene testis promoter. J Biochem (Tokyo) 1997, 121:251-263.
137. Nishimura S, Takahashi S, Kuroha T, Suwabe N, Nagasawa T, Trainor C, Yamamoto M: A GATA box in the GATA-1 gene hematopoietic enhancer is a critical element in the network of GATA factors and sites that regulate this gene. Mol Cell Biol 2000, 20:713-723.
138. Tsang AP, Visvader JE, Turner CA, Fujiwara Y, Yu C, Weiss MJ, Crossley M, Orkin SH: FOG, a multitype zinc finger protein, acts as a cofactor for transcription factor GATA-1 in erythroid and megakaryocytic differentiation. Cell 1997, 90:109-119.
139. Fox AH, Kowalski K, King GF, Mackay JP, Crossley M: Key residues characteristic of GATA N-fingers are recognized by FOG. J Biol Chem 1998, 273:33595-33603.
140. Rekhtman N, Radparvar F, Evans T, Skoultchi AI: Direct interaction of hematopoietic transcription factors PU.1 and GATA-1: functional antagonism in erythroid cells. Genes Dev 1999, 13:1398-1411.
141. Fox AH, Liew C, Holmes M, Kowalski K, Mackay J, Crossley M: Transcriptional cofactors of the FOG family interact with GATA proteins by means of multiple zinc fingers. Embo J 1999, 18:2812-2822.
142. Nerlov C, Querfurth E, Kulessa H, Graf T: GATA-1 interacts with the myeloid PU.1 transcription factor and represses PU.1-dependent transcription. Blood 2000, 95:2543-2551.
143. Zhang P, Zhang X, Iwama A, Yu C, Smith KA, Mueller BU, Narravula S, Torbett BE, Orkin SH, Tenen DG: PU.1 inhibits GATA-1 function and erythroid differentiation by blocking GATA-1 DNA binding. Blood 2000, 96:2641-2648.
144. Merika M, Orkin SH: Functional synergy and physical interactions of the erythroid transcription factor GATA-1 with the Kruppel family proteins Sp1 and EKLF. Mol Cell Biol 1995, 15:2437-2447.
145. Boyes J, Byfield P, Nakatani Y, Ogryzko V: Regulation of activity of the transcription factor GATA-1 by acetylation. Nature 1998, 396:594-598.
146. Hung HL, Lau J, Kim AY, Weiss MJ, Blobel GA: CREB-Binding protein acetylates hematopoietic transcription factor GATA-1 at functionally important sites. Mol Cell Biol 1999, 19:3496-3505.
147. Crossley M, Orkin SH: Phosphorylation of the erythroid transcription factor GATA-1. J Biol Chem 1994, 269:16589-16596.
148. Taxman DJ, Sonsteby SK, Wojchowski DM: In vitro transcription of erythroid promoters using baculoviral-expressed human GATA-1: purification, physicochemistry, and activities. Protein Expr Purif 1994, 5:587-594.
149. Partington GA, Patient RK: Phosphorylation of GATA-1 increases its DNA-binding affinity and is correlated with induction of human K562 erythroleukaemia cells. Nucleic Acids Res 1999, 27:1168-1175.
150. De Maria R, Zeuner A, Eramo A, Domenichelli C, Bonci D, Grignani F, Srinivasula SM, Alnemri ES, Testa U, Peschle C: Negative regulation of erythropoiesis by caspase-mediated cleavage of GATA-1. Nature 1999, 401:489-493.
151. Gregory T, Yu C, Ma A, Orkin SH, Blobel GA, Weiss MJ: GATA-1 and erythropoietin cooperate to promote erythroid cell survival by regulating bcl-xL expression. Blood 1999, 94:87-96.
152. Tanaka H, Matsumura I, Nakajima K, Daino H, Sonoyama J, Yoshida H, Oritani K, Machii T, Yamamoto M, Hirano T, et al.: GATA-1 blocks IL-6-induced macrophage differentiation and apoptosis through the sustained expression of cyclin D1 and bcl-2 in a murine myeloid cell line M1. Blood 2000, 95:1264-1273.
153. Blackwood EM, Kadonaga JT: Going the distance: a current view of enhancer action. Science 1998, 281:61-63.
154. Lee TI, Young RA: Transcription of eukaryotic protein-coding genes. Annu Rev Genet 2000, 34:77-137.
155. Lemon B, Tjian R: Orchestrated response: a symphony of transcription factors for gene control. Genes Dev 2000, 14:2551-2569.
156. Malik S, Roeder RG: Transcriptional regulation through Mediator-like coactivators in yeast and metazoan cells. Trends Biochem Sci 2000, 25:277-283.
157. Orphanides G, Lagrange T, Reinberg D: The general transcription factors of RNA polymerase II. Genes Dev 1996, 10:2657-2683.
158. Smale ST: Transcription initiation from TATA-less promoters within eukaryotic protein-coding genes. Biochim Biophys Acta 1997, 1351:73-88.
159. Lagrange T, Kapanidis AN, Tang H, Reinberg D, Ebright RH: New core promoter element in RNA polymerase II-dependent transcription: sequence-specific DNA binding by transcription factor IIB. Genes Dev 1998, 12:34-44.
160. Smale ST, Baltimore D: The "initiator" as a transcription control element. Cell 1989, 57:103-113.
161. Burke TW, Kadonaga JT: Drosophila TFIID binds to a conserved downstream basal promoter element that is present in many TATA-box-deficient promoters. Genes Dev 1996, 10:711-724.
162. Burke TW, Kadonaga JT: The downstream core promoter element, DPE, is conserved from Drosophila to humans and is recognized by TAFII60 of Drosophila. Genes Dev 1997, 11:3020-3031.
163. Burke TW, Willy PJ, Kutach AK, Butler JE, Kadonaga JT: The DPE, a conserved downstream core promoter element that is functionally analogous to the TATA box. Cold Spring Harb Symp Quant Biol 1998, 63:75-82.
164. Kutach AK, Kadonaga JT: The downstream promoter element DPE appears to be as widely used as the TATA box in Drosophila core promoters. Mol Cell Biol 2000, 20:4754-4764.
165. Smale ST: Core promoters: active contributors to combinatorial gene regulation. Genes Dev 2001, 15:2503-2508.
166. Butler JE, Kadonaga JT: Enhancer-promoter specificity mediated by DPE or TATA core promoter motifs. Genes Dev 2001, 15:2515-2519.
167. Sehgal A, Patil N, Chao M: A constitutive promoter directs expression of the nerve growth factor receptor gene. Mol Cell Biol 1988, 8:3160-3167.
168. Dynan WS, Tjian R: The promoter-specific transcription factor Sp1 binds to upstream sequences in the SV40 early promoter. Cell 1983, 35:79-87.
169. Biggin MD, Tjian R: Transcription factors that activate the Ultrabithorax promoter in developmentally staged extracts. Cell 1988, 53:699-711.
170. Soeller WC, Poole SJ, Kornberg T: In vitro transcription of the Drosophila engrailed gene. Genes Dev 1988, 2:68-81.
171. Perkins KK, Dailey GM, Tjian R: In vitro analysis of the Antennapedia P2 promoter: identification of a new Drosophila transcription factor. Genes Dev 1988, 2:1615-1626.
172. Landau NR, St John TP, Weissman IL, Wolf SC, Silverstone AE, Baltimore D: Cloning of terminal transferase cDNA by antibody screening. Proc Natl Acad Sci U S A 1984, 81:5836-5840.
173. Anderson SJ, Chou HS, Loh DY: A conserved sequence in the T-cell receptor beta-chain promoter region. Proc Natl Acad Sci U S A 1988, 85:3551-3554.
174. Garvin AM, Pawar S, Marth JD, Perlmutter RM: Structure of the murine lck gene and its rearrangement in a murine lymphoma cell line. Mol Cell Biol 1988, 8:3058-3064.
175. Kudo A, Sakaguchi N, Melchers F: Organization of the murine Ig-related lambda 5 gene transcribed selectively in pre-B lymphocytes. Embo J 1987, 6:103-107.
176. Kudo A, Melchers F: A second gene, VpreB in the lambda 5 locus of the mouse, which appears to be selectively expressed in pre-B lymphocytes. Embo J 1987, 6:2267-2272.
177. Grosschedl R, Birnstiel ML: Identification of regulatory sequences in the prelude sequences of an H2A histone gene by the study of specific deletion mutants in vivo. Proc Natl Acad Sci U S A 1980, 77:1432-1436.
178. Breathnach R, Chambon P: Organization and expression of eucaryotic split genes coding for proteins. Annu Rev Biochem 1981, 50:349-383.
179. Smale ST, Schmidt MC, Berk AJ, Baltimore D: Transcriptional activation by Sp1 as directed through TATA or initiator: specific requirement for mammalian transcription factor IID. Proc Natl Acad Sci U S A 1990, 87:4509-4513.
180. Smale ST, Jain A, Kaufmann J, Emami KH, Lo K, Garraway IP: The initiator element: a paradigm for core promoter heterogeneity within metazoan protein-coding genes. Cold Spring Harb Symp Quant Biol 1998, 63:21-31.
181. Sulston JE, Schierenberg E, White JG, Thomson JN: The embryonic cell lineage of the nematode Caenorhabditis elegans. Dev Biol 1983, 100:64-119.
182. Ellis HM, Horvitz HR: Genetic control of programmed cell death in the nematode C. elegans. Cell 1986, 44:817-829.
183. Hengartner MO, Ellis RE, Horvitz HR: Caenorhabditis elegans gene ced-9 protects cells from programmed cell death. Nature 1992, 356:494-499.
184. Ellis RE, Jacobson DM, Horvitz HR: Genes required for the engulfment of cell corpses during programmed cell death in Caenorhabditis elegans. Genetics 1991, 129:79-94.
185. Hedgecock EM, Sulston JE, Thomson JN: Mutations affecting programmed cell deaths in the nematode Caenorhabditis elegans. Science 1983, 220:1277-1279.
186. Sulston JE: Post-embryonic development in the ventral cord of Caenorhabditis elegans. Philos Trans R Soc Lond B Biol Sci 1976, 275:287-297.
187. Yoshihara T, Inaba T, Shapiro LH, Kato JY, Look AT: E2A-HLF-mediated cell transformation requires both the trans-activation domains of E2A and the leucine zipper dimerization domain of HLF. Mol Cell Biol 1995, 15:3247-3255.
188. Palacios R, Steinmetz M: Il-3-dependent mouse clones that express B-220 surface antigen, contain Ig genes in germ-line configuration, and generate B lymphocytes in vivo. Cell 1985, 41:727-734.
189. Lee SF, Huang HM, Chao JR, Lin S, Yang-Yen HF, Yen JJ: Cytokine receptor common beta chain as a potential activator of cytokine withdrawal-induced apoptosis. Mol Cell Biol 1999, 19:7399-7409.
190. Kitamura T, Tange T, Terasawa T, Chiba S, Kuwaki T, Miyagawa K, Piao YF, Miyazono K, Urabe A, Takaku F: Establishment and characterization of a unique human cell line that proliferates dependently on GM-CSF, IL-3, or erythropoietin. J Cell Physiol 1989, 140:323-334.
191. Vinson CR, LaMarco KL, Johnson PF, Landschulz WH, McKnight SL: In situ detection of sequence-specific DNA binding activity specified by a recombinant bacteriophage. Genes Dev 1988, 2:801-806.
192. Dignam JD, Lebovitz RM, Roeder RG: Accurate transcription initiation by RNA polymerase II in a soluble extract from isolated mammalian nuclei. Nucleic Acids Res 1983, 11:1475-1489.
193. Chodosh LA, Carthew RW, Sharp PA: A single polypeptide possesses the binding and transcription activities of the adenovirus major late transcription factor. Mol Cell Biol 1986, 6:4723-4733.
194. Hsueh YP, Liang HE, Ng SY, Lai MZ: CD28-costimulation activates cyclic AMP-responsive element-binding protein in T lymphocytes. J Immunol 1997, 158:85-93.
195. Zheng QA, Chang DC: High-efficiency gene transfection by in situ electroporation of cultured cells. Biochim Biophys Acta 1991, 1088:104-110.
196. Grumont RJ, Rourke IJ, Gerondakis S: Rel-dependent induction of A1 transcription is required to protect B cells from antigen receptor ligation-induced apoptosis. Genes Dev 1999, 13:400-411.
197. Herber B, Truss M, Beato M, Muller R: Inducible regulatory elements in the human cyclin D1 promoter. Oncogene 1994, 9:2105-2107.
198. Stegmann K, Boecker J, Kosan C, Ermert A, Kunz J, Koch MC: Human transcription factor SLUG: mutation analysis in patients with neural tube defects and identification of a missense mutation (D119E) in the Slug subfamily-defining region. Mutat Res 1999, 406:63-69.
199. Sakamoto KM, Fraser JK, Lee HJ, Lehman E, Gasson JC: Granulocyte-macrophage colony-stimulating factor and interleukin-3 signaling pathways converge on the CREB-binding site in the human egr-1 promoter. Mol Cell Biol 1994, 14:5975-5985.
200. Zhang F, Rincon M, Flavell RA, Aune TM: Defective Th function induced by a dominant-negative cAMP response element binding protein mutation is reversed by Bcl-2. J Immunol 2000, 165:1762-1770.
201. Chao JR, Wang JM, Lee SF, Peng HW, Lin YH, Chou CH, Li JC, Huang HM, Chou CK, Kuo ML, et al.: mcl-1 is an immediate-early gene activated by the granulocyte-macrophage colony-stimulating factor (GM-CSF) signaling pathway and is one component of the GM-CSF viability response. Mol Cell Biol 1998, 18:4883-4898.
202. Martin DI, Orkin SH: Transcriptional activation and DNA binding by the erythroid factor GF-1/NF-E1/Eryf 1. Genes Dev 1990, 4:1886-1898.
203. 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 1990, 4:1650-1662.
204. Martin DI, Zon LI, Mutter G, Orkin SH: Expression of an erythroid transcription factor in megakaryocytic and mast cell lineages. Nature 1990, 344:444-447.
205. Romeo PH, Prandini MH, Joulin V, Mignotte V, Prenant M, Vainchenker W, Marguerie G, Uzan G: Megakaryocytic and erythrocytic lineages share specific transcription factors. Nature 1990, 344:447-449.
206. Sposi NM, Zon LI, Care A, Valtieri M, Testa U, Gabbianelli M, Mariani G, Bottero L, Mather C, Orkin SH, et al.: Cell cycle-dependent initiation and lineage-dependent abrogation of GATA-1 expression in pure differentiating hematopoietic progenitors. Proc Natl Acad Sci U S A 1992, 89:6353-6357.
207. Leonard M, Brice M, Engel JD, Papayannopoulou T: Dynamics of GATA transcription factor expression during erythroid differentiation. Blood 1993, 82:1071-1079.
208. 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 1993, 362:466-468.
209. Yomogida K, Ohtani H, Harigae H, Ito E, Nishimune Y, Engel JD, Yamamoto M: Developmental stage- and spermatogenic cycle-specific expression of transcription factor GATA-1 in mouse Sertoli cells. Development 1994, 120:1759-1766.
210. 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 1993, 81:3234-3241.
211. Dorfman DM, Wilson DB, Bruns GA, Orkin SH: Human transcription factor GATA-2. Evidence for regulation of preproendothelin-1 gene expression in endothelial cells. J Biol Chem 1992, 267:1279-1285.
212. Wilson DB, Dorfman DM, Orkin SH: A nonerythroid GATA-binding protein is required for function of the human preproendothelin-1 promoter in endothelial cells. Mol Cell Biol 1990, 10:4854-4862.
213. George KM, Leonard MW, Roth ME, Lieuw KH, Kioussis D, Grosveld F, Engel JD: Embryonic expression and cloning of the murine GATA-3 gene. Development 1994, 120:2673-2686.
214. Kornhauser JM, Leonard MW, Yamamoto M, LaVail JH, Mayo KE, Engel JD: Temporal and spatial changes in GATA transcription factor expression are coincident with development of the chicken optic tectum. Brain Res Mol Brain Res 1994, 23:100-110.
215. Pevny L, Simon MC, Robertson E, Klein WH, Tsai SF, D'Agati V, Orkin SH, Costantini F: Erythroid differentiation in chimaeric mice blocked by a targeted mutation in the gene for transcription factor GATA-1. Nature 1991, 349:257-260.
216. Tsai FY, Keller G, Kuo FC, Weiss M, Chen J, Rosenblatt M, Alt FW, Orkin SH: An early haematopoietic defect in mice lacking the transcription factor GATA-2. Nature 1994, 371:221-226.
217. Weiss MJ, Keller G, Orkin SH: Novel insights into erythroid development revealed through in vitro differentiation of GATA-1 embryonic stem cells. Genes Dev 1994, 8:1184-1197.
218. Rodriguez-Tarduchy G, Collins M, Lopez-Rivas A: Regulation of apoptosis in interleukin-3-dependent hemopoietic cells by interleukin-3 and calcium ionophores. Embo J 1990, 9:2997-3002.
219. Sambrook J, Russell DW: Molecular cloning : a laboratory manual edn 3rd. Cold Spring Harbor, N.Y.: Cold Spring Harbor Laboratory Press; 2001.
220. Sambrook J, Fritsch EF, Maniatis T: Molecular cloning : a laboratory manual edn 2nd. Cold Spring Harbor, N.Y.: Cold Spring Harbor Laboratory; 1989.
221. Chen W, Yu YL, Lee SF, Chiang YJ, Chao JR, Huang JH, Chiong JH, Huang CJ, Lai MZ, Yang-Yen HF, et al.: CREB is one component of the binding complex of the Ces-2/E2A-HLF binding element and is an integral part of the interleukin-3 survival signal. Mol Cell Biol 2001, 21:4636-4646.
222. Wadman IA, Osada H, Grutz GG, Agulnick AD, Westphal H, Forster A, Rabbitts TH: The LIM-only protein Lmo2 is a bridging molecule assembling an erythroid, DNA-binding complex which includes the TAL1, E47, GATA-1 and Ldb1/NLI proteins. Embo J 1997, 16:3145-3157.
223. Saccani S, Pantano S, Natoli G: Two waves of nuclear factor kappaB recruitment to target promoters. J Exp Med 2001, 193:1351-1359.
224. Visvader JE, Crossley M, Hill J, Orkin SH, Adams JM: The C-terminal zinc finger of GATA-1 or GATA-2 is sufficient to induce megakaryocytic differentiation of an early myeloid cell line. Mol Cell Biol 1995, 15:634-641.
225. Huang HM, Li JC, Hsieh YC, Yang-Yen HF, Yen JJ: Optimal proliferation of a hematopoietic progenitor cell line requires either costimulation with stem cell factor or increase of receptor expression that can be replaced by overexpression of Bcl-2. Blood 1999, 93:2569-2577.
226. Tsai FY, Orkin SH: Transcription factor GATA-2 is required for proliferation/survival of early hematopoietic cells and mast cell formation, but not for erythroid and myeloid terminal differentiation. Blood 1997, 89:3636-3643.
227. 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 1995, 11:40-44.
228. Hendriks RW, Nawijn MC, Engel JD, van Doorninck H, Grosveld F, Karis A: Expression of the transcription factor GATA-3 is required for the development of the earliest T cell progenitors and correlates with stages of cellular proliferation in the thymus. Eur J Immunol 1999, 29:1912-1918.
229. Chtanova T, Kemp RA, Sutherland AP, Ronchese F, Mackay CR: Gene microarrays reveal extensive differential gene expression in both CD4(+) and CD8(+) type 1 and type 2 T cells. J Immunol 2001, 167:3057-3063.
230. Towatari M, May GE, Marais R, Perkins GR, Marshall CJ, Cowley S, Enver T: Regulation of GATA-2 phosphorylation by mitogen-activated protein kinase and interleukin-3. J Biol Chem 1995, 270:4101-4107.
231. Yamagata T, Mitani K, Oda H, Suzuki T, Honda H, Asai T, Maki K, Nakamoto T, Hirai H: Acetylation of GATA-3 affects T-cell survival and homing to secondary lymphoid organs. Embo J 2000, 19:4676-4687.
232. Ozawa Y, Towatari M, Tsuzuki S, Hayakawa F, Maeda T, Miyata Y, Tanimoto M, Saito H: Histone deacetylase 3 associates with and represses the transcription factor GATA-2. Blood 2001, 98:2116-2123.
233. Arai KI, Lee F, Miyajima A, Miyatake S, Arai N, Yokota T: Cytokines: coordinators of immune and inflammatory responses. Annu Rev Biochem 1990, 59:783-836.
234. Conscience JF, Verrier B, Martin G: Interleukin-3-dependent expression of the c-myc and c-fos proto-oncogenes in hemopoietic cell lines. Embo J 1986, 5:317-323.
235. Yoshimura A, Ohkubo T, Kiguchi T, Jenkins NA, Gilbert DJ, Copeland NG, Hara T, Miyajima A: A novel cytokine-inducible gene CIS encodes an SH2-containing protein that binds to tyrosine-phosphorylated interleukin 3 and erythropoietin receptors. Embo J 1995, 14:2816-2826.
236. Huang HM, Huang CJ, Yen JJ: Mcl-1 is a common target of stem cell factor and interleukin-5 for apoptosis prevention activity via MEK/MAPK and PI-3K/Akt pathways. Blood 2000, 96:1764-1771.
237. Ferby IM, Waga I, Hoshino M, Kume K, Shimizu T: Wortmannin inhibits mitogen-activated protein kinase activation by platelet-activating factor through a mechanism independent of p85/p110-type phosphatidylinositol 3-kinase. J Biol Chem 1996, 271:11684-11688.
238. Darnell JE, Jr., Kerr IM, Stark GR: Jak-STAT pathways and transcriptional activation in response to IFNs and other extracellular signaling proteins. Science 1994, 264:1415-1421.
239. Ward AC, Touw I, Yoshimura A: The Jak-Stat pathway in normal and perturbed hematopoiesis. Blood 2000, 95:19-29.
240. Orkin SH: Transcription factors and hematopoietic development. J Biol Chem 1995, 270:4955-4958.
241. Clevers HC, Grosschedl R: Transcriptional control of lymphoid development: lessons from gene targeting. Immunol Today 1996, 17:336-343.
242. Clevers H, Ferrier P: Transcriptional control during T-cell development. Curr Opin Immunol 1998, 10:166-171.
243. 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 1998, 9:745-755.
244. 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 1997, 272:21597-21603.
245. Zheng W, Flavell RA: The transcription factor GATA-3 is necessary and sufficient for Th2 cytokine gene expression in CD4 T cells. Cell 1997, 89:587-596.
246. Ting CN, Olson MC, Barton KP, Leiden JM: Transcription factor GATA-3 is required for development of the T-cell lineage. Nature 1996, 384:474-478.
247. Kurata H, Lee HJ, O'Garra A, Arai N: Ectopic expression of activated Stat6 induces the expression of Th2-specific cytokines and transcription factors in developing Th1 cells. Immunity 1999, 11:677-688.
248. Ho IC, Hodge MR, Rooney JW, Glimcher LH: The proto-oncogene c-maf is responsible for tissue-specific expression of interleukin-4. Cell 1996, 85:973-983.
249. Kim JI, Ho IC, Grusby MJ, Glimcher LH: The transcription factor c-Maf controls the production of interleukin-4 but not other Th2 cytokines. Immunity 1999, 10:745-751.
250. Agarwal S, Avni O, Rao A: Cell-type-restricted binding of the transcription factor NFAT to a distal IL-4 enhancer in vivo. Immunity 2000, 12:643-652.

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