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DNA Recognition by NFκB and STAT Transcription Factors

  • Conference paper
Data Mining in Structural Biology

Part of the book series: Ernst Schering Research Foundation Workshop ((SCHERING FOUND,volume 34))

Abstract

The regulated transcription of genes is an important mechanism by which cells control gene expression in response to changing environmental conditions and developmental and apoptotic signals. External and internal cellular signals lead to the activation of transcription factors, which bind to sequence-specific DNA-response elements and stimulate transcription using their trans-activating regions to recruit RNA polymerase to the start site of transcription.

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References

  • Baeuerle PA, Henkel T (1994) Function and activation of NF-KB in the immune system. Annu Rev Immunol 12:141–179

    Article  PubMed  CAS  Google Scholar 

  • Barillas-Mury C, Charlesworth A, Gross I, Richman A, Hoffmann JA, Kafatos FC (1996) Immune factor Gambifl, a new rel family member from the human malaria vector, Anopheles gambiae. EMBO J 15:4961–4701

    Google Scholar 

  • Becker S, Groner B, MÜller CW (1998) Three-dimensional structure of the Stat3β homodimer bound to DNA. Nature 394:145–151

    Article  PubMed  CAS  Google Scholar 

  • Berardi MJ, Sun C, Zehr M, Abildgaard F, Peng J, Speck NA, Bushweller JH (1999) The Ig fold of the core binding factor alpha Runt domain is a member of a family of structurally and functionally related Ig-fold DNA-binding domains. Structure 7:1247–1256

    Article  PubMed  CAS  Google Scholar 

  • Bushdid PB, Brantley DM, Yull FE, Blaeuer GL, Hoffman LH, Niswander L, Kerr LD (1998) Inhibition of NF-KB activity results in disruption of the apical ectodermal ridge and aberrant limb morphogenesis. Nature 392:615–618

    Article  PubMed  CAS  Google Scholar 

  • Carson M (1991) Ribbons 2.0. J Appi Crystallogr 24:958–961

    Article  Google Scholar 

  • Chen FE, Huang D-B, Chen YQ, Ghosh G (1998) Crystal structure of p50/p65 heterodimer of transcription factor NF-KB bound to DNA. Nature 391:410–413

    Article  PubMed  CAS  Google Scholar 

  • Chen L, Glover JNM, Hogan PG, Rao A, Harrison SC (1998) Structure of the DNA-binding domains from NFAT, Fos and Jun bound specifically to DNA. Nature 392:42–48

    Article  PubMed  CAS  Google Scholar 

  • Chen X, Vinkemeier U, Zhao Y, Jeruzalmi D, Darnell JEJ, Kuriyan J (1998) Crystal structure of a tyrosine phosphorylated STAT-1 dimer bound to DNA. Cell 93:827–839

    Article  PubMed  CAS  Google Scholar 

  • Chen YQ, Sengchanthalangsy LL, Hackett A, Ghosh G (2000) NF-KB p65 (RelA) homodimer uses distinct mechanisms to recognize DNA targets. Structure 8:419–428

    Article  PubMed  CAS  Google Scholar 

  • Cho Y, Gorina S, Jeffrey PD, Pavletich NP (1994) Crystal structure of a p53 tumor suppressor-DNA complex: understanding tumorigenic mutations. Science 265:346–355

    Article  PubMed  CAS  Google Scholar 

  • Cramer P, Larson CJ, Verdine GL, Müller CW (1997) Structure of the human NF-KB p52 homodimer-DNA complex at 2.1 à resolution. EMBO J 16:7078–7090

    Article  PubMed  CAS  Google Scholar 

  • Cramer P, Varrot A, Barillas-Mury C, Kafatos FC, MÜller CW (1999) Structure of the specificity domain of the dorsal homologue Gambif 1 bound to DNA. Structure 7:841–852

    Article  PubMed  CAS  Google Scholar 

  • Darnell JE (1997) STATs and Gene regulation. Science 277:1630–1635

    Article  PubMed  CAS  Google Scholar 

  • Dushay MS, Asling B, Hultmark D (1996) Origins of immunity: Relish, a compound Rel-like gene in the antibacterial defense of Drosophila. Proc Natl Acad Sci USA 93:10343–10347

    Article  PubMed  CAS  Google Scholar 

  • Ghosh G, Van Duyne G, Ghosh S, Sigler PB (1995) The structure of NF-KB p50 homodimer bound to a kB site. Nature 373:303–310

    Article  PubMed  CAS  Google Scholar 

  • Ghosh S, May MJ, Kopp EB (1998) NF-KB and Rel proteins: Evolutionary conserved mediators of immune response. Annu Rev Immunol 16:225–260

    Article  PubMed  CAS  Google Scholar 

  • Haan S, Kortylewski M, Behrmann I, Muller-Esterl W, Heinrich PC, Schaper F (2000) Cytoplasmic STAT proteins associate prior to activation. Biochem J 345:417–421

    Article  PubMed  CAS  Google Scholar 

  • Harrison SC (1991) A structural taxonomy of DNA-binding domains. Nature 353:715–719

    Article  PubMed  CAS  Google Scholar 

  • Hatada EN, Krappmann D, Scheidereit C (2000) NF-KB and the innate immune response. Curr Opin Immunol 12:52–58

    Article  PubMed  CAS  Google Scholar 

  • Hoey T, Schindler U (1998) STAT structure and function in signaling. Curr Opin Genes Dev 8:582–587

    Article  CAS  Google Scholar 

  • Horvath CM, Stark GR, Kerr IM, Darnell JE (1996) Interactions between STAT and non-STAT proteins in the interferon-stimulated gene factor 3 transcription complex. Mol Cell Biol 16:6957–6964

    PubMed  CAS  Google Scholar 

  • Hou XS, Melnick MB, Perrimon N (1996) Marelle acts downstream of the Drosophila HOP/JAK kinase and encodes a protein similar to the mammalian STATs. Cell 84:411–419

    Article  PubMed  CAS  Google Scholar 

  • Huxford T, Huang D-B, Malek S, Ghosh G (1998) The crystal structure of the IkBoc-NF-kB complex reveals mechanisms of NF-KB inactivation. Cell 95:759–770

    Article  PubMed  CAS  Google Scholar 

  • Ihle JN (1996) STATs: Signal Transducers and Activators of Transcription. Cell 84:331–334

    Article  PubMed  CAS  Google Scholar 

  • Imler JL, Hoffmann JA (2000) Signaling mechanisms in the antimicrobial host defense of Drosophila. Curr Opin Microbiol 3:16–22

    Article  PubMed  CAS  Google Scholar 

  • Ip YT, Kraut R, Levine M, Rushlow CA (1991) The dorsal morphogen is a sequence-specific DNA-binding protein that interacts with a long-range repression element in Drosophila. Cell 64:439–446

    Article  PubMed  CAS  Google Scholar 

  • Ip YT, Park RE, Kosman D, Yazdanbakhsh K, Levine M (1992) Dorsal-twist interactions establish snail expression in the presumptive mesoderm of the Drosophila embryo. Genes Dev 6:1518–1530

    Article  PubMed  CAS  Google Scholar 

  • Ip YT, Reach M, Engstrom Y, Kadalayil L, Cai H, Gonzalez-Crespo S, Tatei K, Levine M (1993) Dif, a dorsal-related gene that mediates an immune response in Drosophila. Cell 75:753–763

    Article  PubMed  CAS  Google Scholar 

  • Israel A (2000) The IKK complex: an integrator of all signals that activate NF-kB? Trends Cell Biol 10:129–133

    Article  PubMed  CAS  Google Scholar 

  • Jacobs MD, Harrison SC (1998) Structure of an IkBoc/NF-kB complex. Cell 95:749–758

    Article  PubMed  CAS  Google Scholar 

  • Jones KA, Petrlin BM (1994) Control of RNA initiation and elongation at the HIV-1 promoter. Annu Rev Biochem. 63:717–743

    Article  PubMed  CAS  Google Scholar 

  • Kanegae Y, Tavares AT, Belmonte JCI, Verma IM (1998) Role of Rel/NF-KB transcription factors during the outgrowth of the vertebrate limb. Nature 392:611–614

    Article  PubMed  CAS  Google Scholar 

  • Kawata T, Shevchenko A, Fukuzawa M, Jermyn KA, Totty NF, Zhukovskaya NV, Sterling AE, Mann M, Williams JG (1997) SH2 signaling in a lower eukaryote: a STAT protein that regulates stalk cell differentiation in Dic-tyostelium. Cell 89:909–916

    Article  PubMed  CAS  Google Scholar 

  • Meyer WK, Reichenbach P, Schindler U, Soldaini E, Nabholz M (1997) Interaction of STAT5 dimers on two low affinity binding sites mediates inter-leukin 2 (IL-2) stimulation of IL-2 receptor a gene transcription. J Biol Chem 272:31821–31828

    Article  PubMed  CAS  Google Scholar 

  • Mikita T, Campbell D, Wu P, Williamson K, Schindler U (1996) Requirements for interleukin-4-induced gene expression and functional characterization of Stat6. Mol Cell Biol 16:5811–5820

    PubMed  CAS  Google Scholar 

  • MÜller CW, Herrmann B (1997) Crystallographic structure of the T domain-DNA complex of the Brachyury transcription factor. Nature 389:880–884

    Google Scholar 

  • MÜller CW, Rey FA, Harrison SC (1996) Comparison of two different DNA-binding modes of the NF-KB p50 homodimer. Nat Struct Biol 3:224–227

    Article  PubMed  Google Scholar 

  • MÜller CW, Rey FA, Sodeoka M, Verdine GL, Harrison SC (1995) Structure of the NF-KB p50 homodimer bound to DNA. Nature 373:311–317

    Article  PubMed  Google Scholar 

  • Nagata T, Gupta V, Sorce D, Kim WY, Sali A, Chait BT, Shigesada K, Ito Y, Werner MH (1999) Immunoglobulin motif DNA recognition and heterodi-merization of the PEBP2/CBF Runt domain. Nat Struct Biol 6:615–619

    Article  PubMed  CAS  Google Scholar 

  • Ndubuisi MI, Guo GG, Fried VA, Etlinger JD, Sehgal PB (1999) Cellular physiology of STAT3: Where’s the cytoplasmic monomer? J Biol Chem 274:25499–25509

    Article  PubMed  CAS  Google Scholar 

  • Patikoglou G, Burley SK (1997) Eukaryotic transcription factor-DNA complexes. Annu Rev Biophys Biomol Struct 26:289–325

    Article  PubMed  CAS  Google Scholar 

  • Ptashne M (1986) A genetic switch. Blackwell Scientific, Boston

    Google Scholar 

  • Seidel HM, Milocco LH, Lamb P, Darnell JE, Stein RB, Rosen J (1995) Spacing of palindromic half sites as a determinant of selective STAT (signal transducers and activators of transcription) DNA and transcriptional activity. Proc Natl Acad Sci USA 92:3041–3045

    Article  PubMed  CAS  Google Scholar 

  • Sekimoto T, Imamoto N, Nakajima K, Hirano T, Yoneda Y (1997) Extracellular signal dependent nuclear import of Stati is mediated by nuclear pore-targeting complex formation with NPI-1, but not Rchl. EMBO J 16:7067–7077

    Article  PubMed  CAS  Google Scholar 

  • Sengchanthalangsy LL, Datta S, Huang DB, Anderson E, Braswell EH, Ghosh G (1999) Characterization of the dimer interface of transcription factor NFkB p50 homodimer. J Mol Biol 289:1029–1040

    Article  PubMed  CAS  Google Scholar 

  • Sodeoka M, Larson CJ, Chen L, Lane WS, Verdine GL (1993) Limited proteolysis and site-directed mutagenesis of the NF-KB p50 DNA-binding subunit. Biomed Chem Lett. 3:1095–1100

    Article  CAS  Google Scholar 

  • Stancato LF, David M, Carter-Su C, Larner AC (1996) Preassociation of Stati with Stat2 and Stat3 in separate signalling complexes prior to cytokine stimulation. J Biol Chem 271:4134–4137

    Article  PubMed  CAS  Google Scholar 

  • Steward R (1987) Dorsal, an embryonic polarity gene in Drosophila, is homologous to the vertebrate proto-oncogen, c-rel. Science 238:692–694

    Article  PubMed  CAS  Google Scholar 

  • Vinkemeier U, Cohen SL, Moarefi I, Chait BT, Kuriyan J, Darnell JE (1996) DNA binding of in vitro activated Statlα, Stat1β and truncated Stati: interaction between NH2-terminal domains stabilizes binding of two dimers to tandem DNA sites. EMBO J 15:5616–5626

    PubMed  CAS  Google Scholar 

  • Vinkemeier U, Moarefi I, Darnell JE, Kuriyan J (1998) Structure of the amino-terminal protein interaction domain of STAT-4. Science 279:1048–1052

    Article  PubMed  CAS  Google Scholar 

  • Warren AJ, Bravo J, Williams RL, Rabbitts TH (2000) Structural basis for the heterodimeric interaction between the acute leukaemia-associated transcription factors AML1 and CBFbeta. EMBO J 19:3004–3015

    Article  PubMed  CAS  Google Scholar 

  • Xu X, Sun Y-L, Hoey T (1996) Cooperative DNA binding and sequence-selective recognition conferred by the STAT amino-terminal domain. Science 273:794–797

    Article  PubMed  CAS  Google Scholar 

  • Yan R, Small S, Desplan C, Dearolf CR, Darnell JE (1996) Identification of a Stat gene that functions in Drosophila development. Cell 84:421–430

    Article  PubMed  CAS  Google Scholar 

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Authors
  1. C. W. Müller
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Editors and Affiliations

  1. Department of Biophysical Chemistry, Max-Planck-Institute for Molecular Physiology, Otto-Hahn-Strasse 11, 44227, Dortmund, Germany

    I. Schlichting

  2. Research Laboratories, Schering AG, Müllerstrasse 178, 13342, Berlin, Germany

    U. Egner

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© 2001 Springer-Verlag Berlin Heidelberg

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Müller, C.W. (2001). DNA Recognition by NFκB and STAT Transcription Factors. In: Schlichting, I., Egner, U. (eds) Data Mining in Structural Biology. Ernst Schering Research Foundation Workshop, vol 34. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-662-04645-6_8

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  • DOI: https://doi.org/10.1007/978-3-662-04645-6_8

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-662-04647-0

  • Online ISBN: 978-3-662-04645-6

  • eBook Packages: Springer Book Archive

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