The role of Ets transcription factors in the development and function of the mammalian immune system.

Publisher Summary The Ets (E26-transformation specific or E-twenty-six-specific) family of eukaryotic transcription factors is a large (and rapidly growing) set of winged helix-loop-helix DNA-binding proteins all of which recognize a purine-rich sequence motif centered around the core sequence, GGA/T. Invertebrate Ets proteins are both positive and negative regulators of a wide variety of important developmental events, including vulval cell-fate determination in Caenorhabditis elegans and steroid hormone-induced metamorphosis photoreceptor development in Drosophila . The fine mapping of Ets phosphorylation sites and an understanding of the role of individual sites in regulating specific functions, such as DNA binding and protein–protein interactions, will also be essential for understanding the regulation of Ets proteins, as will the elucidation of the signaling pathways that lead to the phosphorylation of Ets proteins following immune cell activation. It is important to identify additional partners that interact with Ets proteins to regulate their transcriptional activities. According to this chapter, recent rapid progress in this field seems safe to predict that the next 5 years will represent a second revolution in the understanding of the role of Ets transcription factors in immune cell function.

[1]  A. Bassuk,et al.  A direct physical association between ETS and AP-1 transcription factors in normal human T cells. , 1995, Immunity.

[2]  M. Tymms,et al.  The Ets1 transcription factor is widely expressed during murine embryo development and is associated with mesodermal cells involved in morphogenetic processes such as organ formation. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[3]  W. Leonard,et al.  Importance of low affinity Elf-1 sites in the regulation of lymphoid- specific inducible gene expression , 1996, The Journal of experimental medicine.

[4]  B. Graves,et al.  Characterization of the cooperative function of inhibitory sequences in Ets-1 , 1996, Molecular and cellular biology.

[5]  A. Sharrocks,et al.  The transcription factors Elk-1 and serum response factor interact by direct protein-protein contacts mediated by a short region of Elk-1 , 1994, Molecular and cellular biology.

[6]  M. Klemsz,et al.  Hematopoietic lineage- and stage-restricted expression of the ETS oncogene family member PU.1. , 1993, Blood.

[7]  S. Hedrick,et al.  Elf-1 binds to a critical element in a second CD4 enhancer , 1994, Molecular and cellular biology.

[8]  T. Oka,et al.  Structural and functional analysis of the regulatory sequences of the ets-1 gene. , 1991, Oncogene.

[9]  J. Ware,et al.  Identification of Essential GATA and Ets Binding Motifs within the Promoter of the Platelet Glycoprotein Ibα Gene (*) , 1995, The Journal of Biological Chemistry.

[10]  A. C. Webb,et al.  Monocyte expression of the human prointerleukin 1 beta gene (IL1B) is dependent on promoter sequences which bind the hematopoietic transcription factor Spi-1/PU.1 , 1995, Molecular and cellular biology.

[11]  F. Alt,et al.  Increased T-cell apoptosis and terminal B-cell differentiation induced by inactivation of the Ets-1 proto-oncogene , 1995, Nature.

[12]  N. Bhat,et al.  Isoforms of the human ets-1 protein: generation by alternative splicing and differential phosphorylation. , 1990, Oncogene.

[13]  M. Klemsz,et al.  The macrophage and B cell-specific transcription factor PU.1 is related to the ets oncogene , 1990, Cell.

[14]  D. Landsman,et al.  Common sequence and structural features in the heat-shock factor and Ets families of DNA-binding domains. , 1995, Trends in biochemical sciences.

[15]  A. Bernstein,et al.  Identification and mapping of a common proviral integration site Fli-1 in erythroleukemia cells induced by Friend murine leukemia virus. , 1990, Proceedings of the National Academy of Sciences of the United States of America.

[16]  L. Klampfer,et al.  Promoter Structure and Transcriptional Activation of the Murine TSG-14 Gene Encoding a Tumor Necrosis Factor/Interleukin-1-inducible Pentraxin Protein (*) , 1995, The Journal of Biological Chemistry.

[17]  E. Olejniczak,et al.  The secondary structure of the ets domain of human Fli-1 resembles that of the helix-turn-helix DNA-binding motif of the Escherichia coli catabolite gene activator protein. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[18]  C. Glass,et al.  Combinatorial interactions between AP-1 and ets domain proteins contribute to the developmental regulation of the macrophage scavenger receptor gene , 1994, Molecular and cellular biology.

[19]  D. Bonthron,et al.  Novel cis-acting elements in the human platelet-derived growth factor B-chain core promoter that mediate gene expression in cultured vascular endothelial cells. , 1994, The Journal of biological chemistry.

[20]  M. Roussel.  Signal transduction by the macrophage-colony-stimulating factor receptor (CSF-1R) , 1994, Journal of Cell Science.

[21]  C. Fisher,et al.  Ligation of membrane Ig leads to calcium-mediated phosphorylation of the proto-oncogene product, Ets-1. , 1991, Journal of immunology.

[22]  S. Galli,et al.  Cloning and functional analysis of the mouse c-kit promoter. , 1993, Biochemical and biophysical research communications.

[23]  A. Sharrocks.  ERK2/p42 MAP kinase stimulates both autonomous and SRF‐dependent DNA binding by Elk‐1 , 1995, FEBS letters.

[24]  M. Roussel,et al.  DNA-binding and transcriptional activation properties of the EWS-FLI-1 fusion protein resulting from the t(11;22) translocation in Ewing sarcoma , 1994, Molecular and cellular biology.

[25]  J. Leiden.  Transcriptional regulation during T-cell development: the α TCR gene as a molecular model , 1992 .

[26]  T. Alber,et al.  Modulation of transcription factor Ets-1 DNA binding: DNA-induced unfolding of an alpha helix. , 1995, Science.

[27]  N. Bhat,et al.  The ets gene family. , 1992, Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research.

[28]  O. Farokhzad,et al.  The human beta 2 integrin CD18 promoter consists of two inverted Ets cis elements , 1994, Molecular and cellular biology.

[29]  R. Fisher,et al.  ets-1 in astrocytes: expression and transmitter-evoked phosphorylation , 1995, Molecular and cellular biology.

[30]  A. Seth,et al.  ETS family proteins activate transcription from HIV-1 long terminal repeat. , 1993, AIDS research and human retroviruses.

[31]  J. H. Chen,et al.  PEA3, Oct 1 and Oct 2 positively regulate the human ETS1 promoter. , 1993, Oncogene.

[32]  P. Romeo,et al.  The Fli-1 proto-oncogene, involved in erythroleukemia and Ewing's sarcoma, encodes a transcriptional activator with DNA-binding specificities distinct from other Ets family members. , 1993, Oncogene.

[33]  A. Giordano,et al.  ets-2 regulates cdc2 kinase activity in mammalian cells: coordinated expression of cdc2 and cyclin A. , 1995, Experimental cell research.

[34]  B. Graves,et al.  Identification of ETS domain proteins in murine T lymphocytes that interact with the Moloney murine leukemia virus enhancer , 1994, Molecular and cellular biology.

[35]  N. Bhat,et al.  Temporal and tissue-specific expression of mouse ets genes. , 1987, Proceedings of the National Academy of Sciences of the United States of America.

[36]  Michael C. Ostrowski,et al.  Ras-mediated phosphorylation of a conserved threonine residue enhances the transactivation activities of c-Ets1 and c-Ets2 , 1996, Molecular and cellular biology.

[37]  K. Struhl,et al.  The TBP-TFIIA interaction in the response to acidic activators in vivo. , 1995, Science.

[38]  N. Bhat,et al.  Phosphorylation of the ETS-2 protein: regulation by the T-cell antigen receptor-CD3 complex , 1990, Molecular and cellular biology.

[39]  S. McKnight,et al.  Convergence of Ets- and notch-related structural motifs in a heteromeric DNA binding complex. , 1991, Science.

[40]  E. E. Max,et al.  Pax5 (BSAP) regulates the murine immunoglobulin 3' alpha enhancer by suppressing binding of NF-alpha P, a protein that controls heavy chain transcription. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[41]  U. Storb,et al.  Pip, a novel IRF family member, is a lymphoid-specific, PU.1-dependent transcriptional activator. , 1995, Genes & development.

[42]  Alfred Nordheim,et al.  Elk-1 protein domains required for direct and SRF-assisted DNA-binding , 1992, Nucleic Acids Res..

[43]  R. J. Fisher,et al.  An intricate arrangement of binding sites for the Ets family of transcription factors regulates activity of the alpha 4 integrin gene promoter. , 1994, The Journal of biological chemistry.

[44]  J. Ghysdael,et al.  Identification of a Ets1 variant protein unaffected in its chromatin and in vitro DNA binding capacities by T cell antigen receptor triggering and intracellular calcium rises. , 1990, Oncogene.

[45]  K. Struhl,et al.  Conserved and nonconserved functions of the yeast and human TATA-binding proteins. , 1994, Genes & development.

[46]  D. Leprince,et al.  Identification and preferential expression in thymic and bursal lymphocytes of a c-ets oncogene-encoded Mr 54,000 cytoplasmic protein. , 1986, Proceedings of the National Academy of Sciences of the United States of America.

[47]  M. Klemsz,et al.  Characterization of the ets oncogene family member, fli-1. , 1993, The Journal of biological chemistry.

[48]  C Terhorst,et al.  Human CD3-epsilon gene contains three miniexons and is transcribed from a non-TATA promoter. , 1988, Proceedings of the National Academy of Sciences of the United States of America.

[49]  N. Copeland,et al.  The murine interleukin-3 receptor alpha subunit gene: chromosomal localization, genomic structure, and promoter function. , 1995, Blood.

[50]  D. Klatzmann,et al.  Characterization of the human CD4 gene promoter: transcription from the CD4 gene core promoter is tissue-specific and is activated by Ets proteins. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[51]  F. Moreau-Gachelin,et al.  Differential phosphorylations of Spi-B and Spi-1 transcription factors. , 1996, Oncogene.

[52]  A M Chumakov,et al.  Localization of the c-ets-2 transactivation domain , 1993, Journal of virology.

[53]  D. Markovitz,et al.  Activation of the human T-cell leukemia virus type I enhancer is mediated by binding sites for Elf-1 and the pets factor , 1993, Journal of virology.

[54]  A. Bernstein,et al.  Erythroleukemia induction by Friend murine leukemia virus: insertional activation of a new member of the ets gene family, Fli-1, closely linked to c-ets-1. , 1991, Genes & development.

[55]  R. Schulz,et al.  Ets oncogene-related gene Elg functions in Drosophila oogenesis. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[56]  J. Leiden.  Transcriptional regulation of T cell receptor genes. , 1993, Annual review of immunology.

[57]  C. Thompson,et al.  Transcriptional regulation of T-cell genes during T-cell development. , 1994, Current opinion in immunology.

[58]  H. Handa,et al.  The retinoblastoma binding factor 1 (RBF-1) site in RB gene promoter binds preferentially E4TF1, a member of the Ets transcription factors family. , 1994, Oncogene.

[59]  A. Chambers,et al.  Identification of a ras-activated enhancer in the mouse osteopontin promoter and its interaction with a putative ETS-related transcription factor whose activity correlates with the metastatic potential of the cell , 1995, Molecular and cellular biology.

[60]  T. Triche,et al.  Combinatorial generation of variable fusion proteins in the Ewing family of tumours. , 1993, The EMBO journal.

[61]  Nic Jones,et al.  Phosphorylation of E2F-1 modulates its interaction with the retinoblastoma gene product and the adenoviral E4 19 kDa protein , 1994, Cell.

[62]  R. Treisman.  Ternary complex factors: growth factor regulated transcriptional activators. , 1994, Current opinion in genetics & development.

[63]  S. O’Brien,et al.  Genomic dispersal of the ets gene family during metazoan evolution. , 1992, Oncogene.

[64]  B. Graves,et al.  Interaction of murine ets-1 with GGA-binding sites establishes the ETS domain as a new DNA-binding motif. , 1992, Genes & development.

[65]  R. Treisman,et al.  Characterization of SAP-1, a protein recruited by serum response factor to the c-fos serum response element , 1992, Cell.

[66]  S. McKnight,et al.  Evidence of DNA: protein interactions that mediate HSV-1 immediate early gene activation by VP16. , 1988, Genes & development.

[67]  J. Lautenberger,et al.  Requirement of ets-2 expression for Xenopus oocyte maturation. , 1990, Science.

[68]  J. Ghysdael,et al.  Identification of nucleotide preferences in DNA sequences recognised specifically by c-Ets-1 protein. , 1992, Nucleic acids research.

[69]  V. Stewart,et al.  RAG-2-deficient mice lack mature lymphocytes owing to inability to initiate V(D)J rearrangement , 1992, Cell.

[70]  A. Sharrocks,et al.  Integration of MAP kinase signal transduction pathways at the serum response element. , 1995, Science.

[71]  H. Horvitz,et al.  The Caenorhabditis elegans gene lin-1 encodes an ETS-domain protein and defines a branch of the vulval induction pathway. , 1995, Genes & development.

[72]  N. Speck,et al.  Cooperative binding of Ets-1 and core binding factor to DNA , 1994, Molecular and cellular biology.

[73]  S. Emerson,et al.  Molecular regulation of the human IL-3 gene: inducible T cell- restricted expression requires intact AP-1 and Elf-1 nuclear protein binding sites , 1993, The Journal of experimental medicine.

[74]  M. Cybulsky,et al.  Structure of the murine VCAM1 gene. , 1993, Genomics.

[75]  M. Shipp,et al.  Analysis of the human CD10/neutral endopeptidase 24.11 promoter region: two separate regulatory elements. , 1995, Blood.

[76]  J. Green,et al.  Differential expression of ets-1 and ets-2 proto-oncogenes during murine embryogenesis. , 1994, Oncogene.

[77]  C. Murre,et al.  Ets proteins: new factors that regulate immunoglobulin heavy-chain gene expression , 1993, Molecular and cellular biology.

[78]  R. Grosschedl,et al.  An inhibitory carboxyl-terminal domain in Ets-1 and Ets-2 mediates differential binding of ETS family factors to promoter sequences of the mb-1 gene. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[79]  F. Moreau-Gachelin,et al.  The Spi‐1/PU.1 and Spi‐B ets family transcription factors and the recombination signal binding protein RBP‐J kappa interact with an Epstein‐Barr virus nuclear antigen 2 responsive cis‐element. , 1994, The EMBO journal.

[80]  Michael C. Ostrowski,et al.  An enhancer element responsive to ras and fms signaling pathways is composed of two distinct nuclear factor binding sites. , 1992, Molecular endocrinology.

[81]  C. Y. Wang,et al.  Regulation of the Ets-related transcription factor Elf-1 by binding to the retinoblastoma protein. , 1993, Science.

[82]  N. Bhat,et al.  Characterization of the human interleukin-2 receptor beta-chain gene promoter: regulation of promoter activity by ets gene products , 1993, Molecular and cellular biology.

[83]  L. Lau,et al.  Activation of the inducible orphan receptor gene nur77 by serum growth factors: dissociation of immediate-early and delayed-early responses , 1993, Molecular and cellular biology.

[84]  J. Green,et al.  Cloning and expression analysis of the murine lymphotoxin beta gene. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[85]  E. Reddy,et al.  A divergent ets-related protein, elk-1, recognizes similar c-ets-1 proto-oncogene target sequences and acts as a transcriptional activator. , 1992, Oncogene.

[86]  F. Bibollet-Ruche,et al.  Serum, AP-1 and Ets-1 stimulate the human ets-1 promoter. , 1992, Nucleic acids research.

[87]  R. Treisman,et al.  Comparative analysis of the ternary complex factors Elk‐1, SAP‐1a and SAP‐2 (ERP/NET). , 1995, The EMBO journal.

[88]  N. Copeland,et al.  Provirus insertion in Tpl-1, an Ets-1-related oncogene, is associated with tumor progression in Moloney murine leukemia virus-induced rat thymic lymphomas. , 1989, Proceedings of the National Academy of Sciences of the United States of America.

[89]  B. Wasylyk,et al.  Net, a new ets transcription factor that is activated by Ras. , 1994, Genes & development.

[90]  H. Prosser,et al.  A phorbol ester response element within the human T-cell receptor beta-chain enhancer. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[91]  Delta elk-1, a variant of elk-1, fails to interact with the serum response factor and binds to DNA with modulated specificity. , 1993, Cancer research.

[92]  W. Vainchenker,et al.  Spi-1/PU.1 transgenic mice develop multistep erythroleukemias , 1996, Molecular and cellular biology.

[93]  J. Forrester,et al.  Regulated expression of the ets-1 transcription factor in vascular smooth muscle cells in vivo and in vitro. , 1996, Circulation research.

[94]  T. Graf,et al.  MafB Is an Interaction Partner and Repressor of Ets-1 That Inhibits Erythroid Differentiation , 1996, Cell.

[95]  S. McKnight,et al.  Identification of Ets- and notch-related subunits in GA binding protein. , 1991, Science.

[96]  J. Ghysdael,et al.  Calcium-induced phosphorylation of ETS1 inhibits its specific DNA binding activity. , 1994, The Journal of biological chemistry.

[97]  T. Graf,et al.  DNA binding by c‐Ets‐1, but not v‐Ets, is repressed by an intramolecular mechanism. , 1992, The EMBO journal.

[98]  L. Shapiro.  Myb and Ets Proteins Cooperate to Transactivate an Early Myeloid Gene (*) , 1995, The Journal of Biological Chemistry.

[99]  S. Subramani,et al.  The late promoter of the human papovavirus BK is contained within the early promoter enhancer region. , 1988, Virology.

[100]  J. D. Thomas,et al.  Genomic organization of mouse and human Bruton's agammaglobulinemia tyrosine kinase (Btk) loci. , 1994, Journal of immunology.

[101]  V. N. Roa,et al.  Ets-related protein Elk-1 is homologous to the c-fos regulatory factor p62TCF , 1991, Nature.

[102]  M. Pazin,et al.  Activation of the HIV-1 enhancer by the LEF-1 HMG protein on nucleosome-assembled DNA in vitro. , 1995, Genes & development.

[103]  J. Brady,et al.  The product of the c‐ets‐1 proto‐oncogene and the related Ets2 protein act as transcriptional activators of the long terminal repeat of human T cell leukemia virus HTLV‐1. , 1990, The EMBO journal.

[104]  B. Kistler,et al.  Lymphoid- and myeloid-specific activity of the PU.1 promoter is determined by the combinatorial action of octamer and ets transcription factors. , 1995, Oncogene.

[105]  PU.1 is a component of a multiprotein complex which binds an essential site in the murine immunoglobulin lambda 2-4 enhancer. , 1993, Molecular and cellular biology.

[106]  A. Hassett,et al.  Lipopolysaccharide induction of tissue factor expression in THP-1 monocytic cells. Protein-DNA interactions with the promoter. , 1994, The Journal of biological chemistry.

[107]  P. Tucker,et al.  Functional analysis of the V gamma 3 promoter of the murine gamma delta T-cell receptor , 1994, Molecular and cellular biology.

[108]  D. Markovitz,et al.  Differential regulation of the human immunodeficiency virus type 2 enhancer in monocytes at various stages of differentiation , 1993, Journal of virology.

[109]  P. Coffer,et al.  junB promoter regulation: Ras mediated transactivation by c-Ets-1 and c-Ets-2. , 1994, Oncogene.

[110]  A. Nordheim,et al.  Functional dissection of the transcription factor Elk-1. , 1994, Oncogene.

[111]  R. Gaynor,et al.  Regulatory elements involved in tax-mediated transactivation of the HTLV-I LTR. , 1993, Virology.

[112]  C. Begley,et al.  Lineage-restricted regulation of the murine SCL/TAL-1 promoter. , 1995, Blood.

[113]  Huei-Mei Chen,et al.  Pi 1 binding sites are negative regulators of bcl-2 expression in pre-B cells , 1995, Molecular and cellular biology.

[114]  R. Meadows,et al.  Solution structure of the ets domain of Fli-1 when bound to DNA , 1994, Nature Structural Biology.

[115]  K. Gollahon,et al.  Identification of the promoter of the myelomonocytic leukocyte integrin CD11b. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[116]  C. Thummel,et al.  Molecular interactions within the ecdysone regulatory hierarchy: DNA binding properties of the Drosophila ecdysone-inducible E74A protein , 1990, Cell.

[117]  C. Y. Wang,et al.  A novel Ets-related transcription factor, Elf-1, binds to human immunodeficiency virus type 2 regulatory elements that are required for inducible trans activation in T cells , 1992, Journal of virology.

[118]  D. Tenen,et al.  PU.1 (Spi-1) autoregulates its expression in myeloid cells. , 1995, Oncogene.

[119]  F. Moreau-Gachelin,et al.  DNA binding specificities of Spi-1/PU.1 and Spi-B transcription factors and identification of a Spi-1/Spi-B binding site in the c-fes/c-fps promoter. , 1995, Oncogene.

[120]  M. Fenton,et al.  NF beta A, a factor required for maximal interleukin-1 beta gene expression is identical to the ets family member PU.1. Evidence for structural alteration following LPS activation. , 1995, Molecular immunology.

[121]  J. Brady,et al.  Sequence-specific interaction of the Ets1 protein with the long terminal repeat of the human T-lymphotropic virus type I , 1991, Journal of virology.

[122]  F. Moreau-Gachelin,et al.  Involvement of the transcription factor PU.1/Spi-1 in myeloid cell-restricted expression of an interferon-inducible gene encoding the human high-affinity Fc gamma receptor , 1994, Molecular and cellular biology.

[123]  M. Simon,et al.  The Ets protein Spi-B is expressed exclusively in B cells and T cells during development , 1996, The Journal of experimental medicine.

[124]  Yoav Goldberg,et al.  Repression of AP-1-stimulated transcription by c-Ets-1. , 1994, The Journal of biological chemistry.

[125]  N. Sugg,et al.  The integrin alpha v gene: identification and characterization of the promoter region. , 1994, Biochimica et biophysica acta.

[126]  M. Plumb,et al.  C/EBP, NF-kappa B, and c-Ets family members and transcriptional regulation of the cell-specific and inducible macrophage inflammatory protein 1 alpha immediate-early gene , 1993, Molecular and cellular biology.

[127]  E. Reddy,et al.  Elk-1 proteins are phosphoproteins and activators of mitogen-activated protein kinase. , 1993, Cancer research.

[128]  J. H. Chen.  The proto-oncogene c-ets is preferentially expressed in lymphoid cells , 1985, Molecular and cellular biology.

[129]  T. Hirano,et al.  Identification of a novel interleukin-6 response element containing an Ets-binding site and a CRE-like site in the junB promoter , 1993, Molecular and cellular biology.

[130]  N. Avadhani,et al.  The basal promoter elements of murine cytochrome c oxidase subunit IV gene consist of tandemly duplicated ets motifs that bind to GABP-related transcription factors. , 1992, The Journal of biological chemistry.

[131]  B. Davis,et al.  Isolation and molecular characterization of the human CD34 gene. , 1992, Blood.

[132]  G. Henkel,et al.  PU.1 and GATA: components of a mast cell-specific interleukin 4 intronic enhancer. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[133]  A. Bernstein,et al.  Generation of a novel Fli-1 protein by gene targeting leads to a defect in thymus development and a delay in Friend virus-induced erythroleukemia , 1996, Molecular and cellular biology.

[134]  Andrew J. Bannister,et al.  The activation domain of transcription factor PU.1 binds the retinoblastoma (RB) protein and the transcription factor TFIID in vitro: RB shows sequence similarity to TFIID and TFIIB. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[135]  G. Pauli,et al.  Sequence specific binding of the transcription factor c-Ets1 to the human immunodeficiency virus type I long terminal repeat. , 1993, Biochemical and biophysical research communications.

[136]  R. Wall,et al.  Multiple motifs regulate the B-cell-specific promoter of the B29 gene. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[137]  C. Glass,et al.  Scavenger receptor A gene regulatory elements target gene expression to macrophages and to foam cells of atherosclerotic lesions. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[138]  K. Gaston,et al.  CpG methylation and the binding of YY1 and ETS proteins to the Surf-1/Surf-2 bidirectional promoter. , 1995, Gene.

[139]  C. Thompson,et al.  The FLI-1 and chimeric EWS-FLI-1 oncoproteins display similar DNA binding specificities. , 1994, The Journal of biological chemistry.

[140]  K. Gaston,et al.  CpG methylation has differential effects on the binding of YY1 and ETS proteins to the bi-directional promoter of the Surf-1 and Surf-2 genes. , 1995, Nucleic acids research.

[141]  D. Wotton,et al.  The High Mobility Group Transcription Factor, SOX4, Transactivates the Human CD2 Enhancer (*) , 1995, The Journal of Biological Chemistry.

[142]  D. Leprince,et al.  A putative second cell-derived oncogene of the avian leukaemia retrovirus E26 , 1983, Nature.

[143]  B. Graves,et al.  Sequence-specific DNA binding of the proto-oncoprotein ets-1 defines a transcriptional activator sequence within the long terminal repeat of the Moloney murine sarcoma virus. , 1990, Genes & development.

[144]  R. Kodandapani,et al.  A new pattern for helix–turn–helix recognition revealed by the PU.l ETS–domain–DNA complex , 1996, Nature.

[145]  L. Johnson,et al.  In vitro transcription of the TATAA-less mouse thymidylate synthase promoter: multiple transcription start points and evidence for bidirectionality. , 1994, Gene.

[146]  C. Hauser,et al.  Oncogenic Ras can induce transcriptional activation through a variety of promoter elements, including tandem c-Ets-2 binding sites. , 1994, Oncogene.

[147]  A. Seth,et al.  ETS1 and ETS2 in p53 regulation: spatial separation of ETS binding sites (EBS) modulate protein: DNA interaction. , 1996, Oncogene.

[148]  O. Farokhzad,et al.  Identification of cell-specific and developmentally regulated nuclear factors that direct myeloid and lymphoid expression of the CD11a gene. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[149]  B. Vandenbunder,et al.  Involvement of the proto-oncogene c-ets 1 and the urokinase plasminogen activator during mouse implantation and placentation. , 1993, The International journal of developmental biology.

[150]  P. Grant,et al.  IgM receptor‐mediated transactivation of the IgH 3′ enhancer couples a novel Elf‐1‐AP‐1 protein complex to the developmental control of enhancer function. , 1995, The EMBO journal.

[151]  W. Leonard,et al.  Regulation of cell-type-specific interleukin-2 receptor alpha-chain gene expression: potential role of physical interactions between Elf-1, HMG-I(Y), and NF-kappa B family proteins , 1995, Molecular and cellular biology.

[152]  B. Wasylyk,et al.  The oncoprotein v-Ets is less selective in DNA binding than c-Ets-1 due to the C-terminal sequence change. , 1994, Oncogene.

[153]  J. Ghysdael,et al.  A single amino-acid substitution in the Ets domain alters core DNA binding specificity of Ets1 to that of the related transcription factors Elf1 and E74. , 1993, Nucleic acids research.

[154]  G. Thomas,et al.  Gene fusion with an ETS DNA-binding domain caused by chromosome translocation in human tumours , 1992, Nature.

[155]  C. Kozak,et al.  The Sfpi-1 proviral integration site of Friend erythroleukemia encodes the ets-related transcription factor Pu.1 , 1991, Journal of virology.

[156]  C. J. Barnett,et al.  Opposing actions of c-ets/PU.1 and c-myb protooncogene products in regulating the macrophage-specific promoters of the human and mouse colony-stimulating factor-1 receptor (c-fms) genes , 1994, The Journal of experimental medicine.

[157]  M. Klemsz,et al.  The ETS oncogene family in development, proliferation and neoplasia. , 1994, International journal of hematology.

[158]  M. Campbell,et al.  Transcription of the blk Gene in Human B Lymphocytes Is Controlled by Two Promoters (*) , 1995, The Journal of Biological Chemistry.

[159]  B. Wasylyk,et al.  The c-ets proto-oncogenes encode transcription factors that cooperate with c-Fos and c-Jun for transcriptional activation , 1990, Nature.

[160]  B. Kwon,et al.  Identification of a killer cell-specific regulatory element of the mouse perforin gene: an Ets-binding site-homologous motif that interacts with Ets-related proteins , 1993, Molecular and cellular biology.

[161]  B. Aronow,et al.  Functional analysis of the human adenosine deaminase gene thymic regulatory region and its ability to generate position-independent transgene expression , 1992, Molecular and cellular biology.

[162]  P. Kavathas,et al.  Identification and characterization of an Alu-containing, T-cell-specific enhancer located in the last intron of the human CD8 alpha gene , 1993, Molecular and cellular biology.

[163]  N. Tanaka,et al.  Functional Analysis of the Human Interleukin 2 Receptor γ Chain Gene Promoter (*) , 1995, The Journal of Biological Chemistry.

[164]  T. Libermann,et al.  ERP, a new member of the ets transcription factor/oncoprotein family: cloning, characterization, and differential expression during B-lymphocyte development , 1994, Molecular and cellular biology.

[165]  R. Ueda,et al.  pokkuri, a Drosophila gene encoding an E-26-specific (Ets) domain protein, prevents overproduction of the R7 photoreceptor. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[166]  B. Peterlin,et al.  Ets-1 activates the DRA promoter in B cells , 1994, Molecular and cellular biology.

[167]  Z. Werb,et al.  Synergistic Transcriptional Activation of the Tissue Inhibitor of Metalloproteinases-1 Promoter via Functional Interaction of AP-1 and Ets-1 Transcription Factors (*) , 1996, The Journal of Biological Chemistry.

[168]  P. Shaw,et al.  Phosphorylation-dependent formation of a quaternary complex at the c-fos SRE , 1996, Molecular and cellular biology.

[169]  M. Pazin,et al.  NF-kappa B-mediated chromatin reconfiguration and transcriptional activation of the HIV-1 enhancer in vitro. , 1996, Genes & development.

[170]  K. Struhl,et al.  Mutations on the DNA-binding surface of TATA-binding protein can specifically impair the response to acidic activators in vivo , 1995, Molecular and cellular biology.

[171]  M. Klemsz,et al.  Effect of PU.1 phosphorylation on interaction with NF-EM5 and transcriptional activation. , 1993, Science.

[172]  J. Newell,et al.  Involvement of the Ets Family Factor PU.1 in the Activation of Immunoglobulin Promoters (*) , 1995, The Journal of Biological Chemistry.

[173]  H. Nasheuer,et al.  Human DNA polymerase alpha gene: sequences controlling expression in cycling and serum-stimulated cells , 1991, Molecular and cellular biology.

[174]  J. Ghysdael,et al.  Mitogenic stimulation of thymocytes results in the calcium‐dependent phosphorylation of c‐ets‐1 proteins. , 1988, The EMBO journal.

[175]  Y. Yazaki,et al.  Transcription factor PU.1 mediates induction of c-fms in vascular smooth muscle cells: a mechanism for phenotypic change to phagocytic cells , 1996, Molecular and cellular biology.

[176]  J. Ghysdael,et al.  Requirement of an ETS-binding element for transcription of the human lck type I promoter. , 1993, Oncogene.

[177]  B. Wasylyk,et al.  The Ets family of transcription factors. , 1993, European journal of biochemistry.

[178]  C. Y. Wang,et al.  Activation of the granulocyte-macrophage colony-stimulating factor promoter in T cells requires cooperative binding of Elf-1 and AP-1 transcription factors , 1994, Molecular and cellular biology.

[179]  N. Speck,et al.  Transactivation of the Moloney murine leukemia virus and T-cell receptor beta-chain enhancers by cbf and ets requires intact binding sites for both proteins , 1995, Journal of virology.

[180]  R. J. Fisher,et al.  ERF: an ETS domain protein with strong transcriptional repressor activity, can suppress ets‐associated tumorigenesis and is regulated by phosphorylation during cell cycle and mitogenic stimulation. , 1995, The EMBO journal.

[181]  M. Klemsz,et al.  The ETS-domain: a new DNA-binding motif that recognizes a purine-rich core DNA sequence. , 1990, Genes & development.

[182]  E. Scott,et al.  Requirement of transcription factor PU.1 in the development of multiple hematopoietic lineages. , 1994, Science.

[183]  F. Propst,et al.  Ets-1 and Ets-2 protooncogene expression in theca cells of the adult mouse ovary. , 1992, Experimental cell research.

[184]  M. Mattei,et al.  Characterization of Spi-B, a transcription factor related to the putative oncoprotein Spi-1/PU.1 , 1992, Molecular and cellular biology.

[185]  M. Krönke,et al.  Regulation of the Human TNF Promoter by the Transcription Factor Ets (*) , 1995, The Journal of Biological Chemistry.

[186]  D. Hogness,et al.  The Drosophila 74EF early puff contains E74, a complex ecdysone-inducible gene that encodes two ets-related proteins , 1990, Cell.

[187]  S. Smale,et al.  Both LyF-1 and an Ets protein interact with a critical promoter element in the murine terminal transferase gene , 1993, Molecular and cellular biology.

[188]  E. Scott,et al.  PU. 1 is not essential for early myeloid gene expression but is required for terminal myeloid differentiation. , 1995, Immunity.

[189]  N. Bhat,et al.  Sequence-specific binding of human Ets-1 to the T cell receptor alpha gene enhancer. , 1990, Science.

[190]  M. Shibuya,et al.  Characterization of the Promoter Region of the Human c‐kit Proto‐oncogene , 1993, Japanese journal of cancer research : Gann.

[191]  M. Tymms,et al.  Down's syndrome-like skeletal abnormalities in Ets2 transgenic mice , 1996, Nature.

[192]  Andrew D. Sharrocks,et al.  DNA bending in the ternary nucleoprotein complex at the c-fos promoter , 1995, Nucleic Acids Res..

[193]  B. Peterlin.  Transcriptional regulation of HLA-DRA gene. , 1991, Research in immunology.

[194]  M. Atchison,et al.  Multiple proteins physically interact with PU.1. Transcriptional synergy with NF-IL6 beta (C/EBP delta, CRP3). , 1995, Journal of immunology.

[195]  E. Reddy,et al.  Structure and expression of human Fli-1 gene. , 1992, Cancer research.

[196]  Rao Vn,et al.  elk-1 domains responsible for autonomous DNA binding, SRE:SRF interaction and negative regulation of DNA binding. , 1992 .

[197]  E. Reddy,et al.  Analysis of the DNA-binding and transcriptional activation functions of human Fli-1 protein. , 1993, Oncogene.

[198]  R. Fotedar,et al.  Mapping of an inducible element in the T cell receptor V beta 2 promoter. , 1992, Journal of immunology.

[199]  B. Erman,et al.  Regulation of lymphoid-specific immunoglobulin mu heavy chain gene enhancer by ETS-domain proteins. , 1993, Science.

[200]  H. Handa,et al.  GABP and PU.1 Compete for Binding, yet Cooperate to Increase CD18 (β2 Leukocyte Integrin) Transcription (*) , 1995, The Journal of Biological Chemistry.

[201]  A. Nordheim,et al.  SAP1a is a nuclear target of signaling cascades involving ERKs. , 1995, Oncogene.

[202]  Richard Treisman,et al.  Functional analysis of a growth factor-responsive transcription factor complex , 1993, Cell.

[203]  C. Glass,et al.  Cell-specific expression of the macrophage scavenger receptor gene is dependent on PU.1 and a composite AP-1/ets motif , 1994, Molecular and cellular biology.

[204]  P. Romeo,et al.  GATA and Ets cis-acting sequences mediate megakaryocyte-specific expression , 1993, Molecular and cellular biology.

[205]  D. Leprince,et al.  c-ets-1 DNA binding to the PEA3 motif is differentially inhibited by all the mutations found in v-ets. , 1992, Oncogene.

[206]  R. Treisman,et al.  The SRF accessory protein Elk-1 contains a growth factor-regulated transcriptional activation domain , 1993, Cell.

[207]  D. Markovitz,et al.  Activation of the human immunodeficiency virus type 2 enhancer is dependent on purine box and kappa B regulatory elements , 1992, Journal of virology.

[208]  J. Coligan,et al.  Multiple cis-acting elements are required for proper transcription of the mouse V delta 1 T cell receptor promoter. , 1993, Journal of immunology.

[209]  M. Klemsz,et al.  PU.1 recruits a second nuclear factor to a site important for immunoglobulin kappa 3' enhancer activity , 1992, Molecular and cellular biology.

[210]  M. Simon,et al.  The myeloid-cell-specific c-fes promoter is regulated by Sp1, PU.1, and a novel transcription factor , 1996, Molecular and cellular biology.

[211]  P. Grant,et al.  Identification of Ets-like lymphoid specific elements within the immunoglobulin heavy chain 3' enhancer. , 1992, Nucleic acids research.

[212]  S. Rogers,et al.  Amino acid sequences common to rapidly degraded proteins: the PEST hypothesis. , 1986, Science.

[213]  S. Watson,et al.  Cytosolic Phospholipase A2 Is Phosphorylated in Collagen- and Thrombin-stimulated Human Platelets Independent of Protein Kinase C and Mitogen-activated Protein Kinase (*) , 1995, The Journal of Biological Chemistry.

[214]  D. Leprince,et al.  Evolution of the ets gene family. , 1993, Biochemical and biophysical research communications.

[215]  S. Saule,et al.  Oncogenes and avian development. , 1990, The International journal of developmental biology.

[216]  N. Muthusamy,et al.  Defective activation and survival of T cells lacking the Ets-1 transcription factor , 1995, Nature.

[217]  J. Cazenave,et al.  Cloning and characterization of the gene encoding the human platelet glycoprotein V. A member of the leucine-rich glycoprotein family cleaved during thrombin-induced platelet activation. , 1993, The Journal of biological chemistry.

[218]  M. Yamaguchi,et al.  Mouse DNA polymerase beta gene promoter: fine mapping and involvement of Sp1-like mouse transcription factor in its function. , 1988, Nucleic acids research.

[219]  P. Romeo,et al.  Structure and transcription of the human c-mpl gene (MPL). , 1994, Genomics.

[220]  P. Seeburg,et al.  Tripartite structure of the avian erythroblastosis virus E26 transforming gene , 1983, Nature.

[221]  G. Mavrothalassitis,et al.  Molecular and functional characterization of the promoter of ETS2, the human c-ets-2 gene. , 1990, Proceedings of the National Academy of Sciences of the United States of America.

[222]  B. Degnan,et al.  The ets multigene family is conserved throughout the Metazoa. , 1993, Nucleic acids research.

[223]  R. Fisher,et al.  Structural inferences of the ETS1 DNA-binding domain determined by mutational analysis. , 1994, Oncogene.

[224]  D. Leprince,et al.  The ets gene family. , 1992, Trends in biochemical sciences.

[225]  R Grosschedl,et al.  Assembly and function of a TCR alpha enhancer complex is dependent on LEF-1-induced DNA bending and multiple protein-protein interactions. , 1995, Genes & development.

[226]  Gerald M. Rubin,et al.  The activities of two Ets-related transcription factors required for drosophila eye development are modulated by the Ras/MAPK pathway , 1994, Cell.

[227]  N. Bhat,et al.  A short-lived nuclear phosphoprotein encoded by the human ets-2 proto-oncogene is stabilized by activation of protein kinase C , 1988, Molecular and cellular biology.

[228]  M. Klemsz,et al.  Activation of transcription by PU.1 requires both acidic and glutamine domains , 1996, Molecular and cellular biology.

[229]  M. K. Shin,et al.  Ets-related protein PU.1 regulates expression of the immunoglobulin J-chain gene through a novel Ets-binding element. , 1993, Genes & development.

[230]  Ajay N. Jain,et al.  E.: “A Summary of , 1968 .

[231]  C. Y. Wang,et al.  cis-acting sequences required for inducible interleukin-2 enhancer function bind a novel Ets-related protein, Elf-1 , 1992, Molecular and cellular biology.

[232]  Michael C. Ostrowski,et al.  Mitogenic signaling by colony-stimulating factor 1 and ras is suppressed by the ets-2 DNA-binding domain and restored by myc overexpression , 1992, Molecular and cellular biology.

[233]  C. Thummel,et al.  The Drosophila E74 gene is required for the proper stage- and tissue-specific transcription of ecdysone-regulated genes at the onset of metamorphosis. , 1995, Development.

[234]  H. Sakano,et al.  The 3′ enhancer region determines the B/T specificity and pro-B/pre-B specificity of immunoglobulin Vκ-Jκ joining , 1995, Cell.

[235]  J. Ghysdael,et al.  Myb and Ets related transcription factors are required for activity of the human lck type I promoter. , 1994, Oncogene.

[236]  J. Lautenberger,et al.  Interaction of ETS-1 and ERGB/FLI-1 proteins with DNA is modulated by spacing between multiple binding sites as well as phosphorylation. , 1996, Oncogene.

[237]  A. Czernik,et al.  Anti-immunoglobulin M activates nuclear calcium/calmodulin-dependent protein kinase II in human B lymphocytes , 1995, The Journal of experimental medicine.

[238]  S. McKnight,et al.  Purification of a set of cellular polypeptides that bind to the purine-rich cis-regulatory element of herpes simplex virus immediate early genes. , 1989, Genes & development.

[239]  R. Schulz,et al.  D-elg, a member of the Drosophila ets gene family: sequence, expression and evolutionary comparison. , 1991, Oncogene.

[240]  O. Witte,et al.  Distinctive growth requirements and gene expression patterns distinguish progenitor B cells from pre-B cells , 1993, The Journal of experimental medicine.

[241]  T. Oka,et al.  Negative regulatory elements in the human ETS1 gene promoter. , 1993, Oncogene.

[242]  D. Tenen,et al.  PU.1 (Spi-1) and C/EBP alpha regulate expression of the granulocyte-macrophage colony-stimulating factor receptor alpha gene , 1995, Molecular and cellular biology.

[243]  K. Yano,et al.  cDNA cloning of transcription factor E4TF1 subunits with Ets and notch motifs , 1993, Molecular and cellular biology.

[244]  W S Moye-Rowley,et al.  GSH1, which encodes gamma-glutamylcysteine synthetase, is a target gene for yAP-1 transcriptional regulation. , 1994, Molecular and cellular biology.

[245]  Gerald M. Rubin,et al.  Negative control of photoreceptor development in Drosophila by the product of the yan gene, an ETS domain protein , 1992, Cell.

[246]  R. Treisman,et al.  Spatial flexibility in ternary complexes between SRF and its accessory proteins. , 1992, The EMBO journal.

[247]  Antonio Celada,et al.  Repression of I-Aβ Gene Expression by the Transcription Factor PU.1 (*) , 1995, The Journal of Biological Chemistry.

[248]  B. Wasylyk,et al.  Reversion of Ras transformed cells by Ets transdominant mutants. , 1994, Oncogene.

[249]  S. McMahon,et al.  A ternary complex factor-dependent mechanism mediates induction of egr-1 through selective serum response elements following antigen receptor cross-linking in B lymphocytes , 1995, Molecular and cellular biology.