Understanding the logic of IκB:NF-κB regulation in structural terms

Current Topics in Microbiology and Immunology

Volumn 349, Issue , 2011, Pages 1-24

  Huxford, Tom ^a   Hoffmann, Alexander ^b   Ghosh, Gourisankar ^b  

^a SAN DIEGO STATE UNIVERSITY   (United States)

^b UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

I KAPPA B; I KAPPA B KINASE ALPHA; I KAPPA B KINASE EPSILON; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; PROTEIN P100; PROTEIN P105; TRANSCRIPTION FACTOR RELA; DNA; I KAPPA B KINASE;

ARTICLE; BINDING AFFINITY; DIMERIZATION; DNA PROTEIN COMPLEX; DNA SEQUENCE; MOLECULAR RECOGNITION; NONHUMAN; PRIORITY JOURNAL; PROTEIN DEGRADATION; PROTEIN DNA BINDING; PROTEIN FUNCTION; PROTEIN INDUCTION; PROTEIN LOCALIZATION; PROTEIN PROCESSING; PROTEIN STABILITY; PROTEIN STRUCTURE; REGULATORY MECHANISM; STRUCTURE ANALYSIS; TRANSCRIPTION REGULATION; ANIMAL; CELL NUCLEUS; CHEMISTRY; HUMAN; METABOLISM; PHYSIOLOGY; PROTEIN MULTIMERIZATION; REVIEW;

MAMMALIA;

ANIMALS; CELL NUCLEUS; DNA; HUMANS; I-KAPPA B KINASE; NF-KAPPA B; PROTEIN MULTIMERIZATION;

EID: 84859974128     PISSN: 0070217X     EISSN: None     Source Type: Book Series    
DOI: 10.1007/82-2010-99     Document Type: Article

References (80)

1. Basak S, Kim H, Kearns JD, Tergaonkar V, O'Dea E, Werner SL, Benedict CA, Ware CF, Ghosh G, Verma IM, Hoffmann A (2007) A fourth IκB protein within the NF-κB signaling module. Cell 128:369-381 (Pubitemid 46123518)
2. Basak S, Shih VF, Hoffmann A (2008) Generation and activation of multiple dimeric transcription factors within the NF-κB signaling system. Mol Cell Biol 28:3139-3150 (Pubitemid 351657080)
3. Bergqvist S, Croy CH, Kjaergaard M, Huxford T, Ghosh G, Komives EA (2006) Thermodynamics reveal that helix four in the NLS of NF-κB p65 anchors IκBα, forming a very stable complex. J Mol Biol 360:421-434 (Pubitemid 43927832)
4. Bergqvist S, Alverdi V, Mengel B, Hoffmann A, Ghosh G, Komives EA (2009) Kinetic enhancement of NF-κB:DNA dissociation by IκBα. Proc Natl Acad Sci USA 106:19328-19333
5. Berkowitz B, Huang DB, Chen-Park FE, Sigler PB, Ghosh G (2002) The X-ray crystal structure of the NF-κ B p50.p65 heterodimer bound to the interferon beta-κB site. J Biol Chem 277:24694-24700 (Pubitemid 34952000)
6. Bork P (1993) Hundreds of ankyrin-like repeats in functionally diverse proteins: mobile modules that cross phyla horizontally? Proteins 17:363-374
7. Chang M, Lee AJ, Fitzpatrick L, Zhang M, Sun SC (2009) NF-κ B1 p105 regulates T cell homeostasis and prevents chronic inflammation. J Immunol 182:3131-3138
8. Chen ZJ (2005) Ubiquitin signalling in the NF-κB pathway. Nat Cell Biol 7:758-765
9. Chen FE, Huang DB, Chen YQ, Ghosh G (1998a) Crystal structure of p50/p65 heterodimer of transcription factor NF-κB bound to DNA. Nature 391:410-413
10. Chen YQ, Ghosh S, Ghosh G (1998b) A novel DNA recognition mode by the NF-κ B p65 homodimer. Nat Struct Biol 5:67-73 (Pubitemid 28048979)
11. Chen YQ, Sengchanthalangsy LL, Hackett A, Ghosh G (2000) NF-κB p65 (RelA) homodimer uses distinct mechanisms to recognize DNA targets. Structure 8:419-428 (Pubitemid 30202902)
12. Chen Y, Vallee S, Wu J, Vu D, Sondek J, Ghosh G (2004) Inhibition of NF-κB activity by IκBbeta in association with κB-Ras. Mol Cell Biol 24:3048-3056 (Pubitemid 38381291)
13. Chen-Park FE, Huang DB, Noro B, Thanos D, Ghosh G (2002) The κB DNA sequence from the HIV long terminal repeat functions as an allosteric regulator of HIV transcription. J Biol Chem 277:24701-24708 (Pubitemid 34952001)
14. Conti E, Kuriyan J (2000) Crystallographic analysis of the specific yet versatile recognition of distinct nuclear localization signals by karyopherin alpha. Structure 8:329-338 (Pubitemid 30148698)
15. Cramer P, Larson CJ, Verdine GL, Müller CW (1997) Structure of the human NF-κB p52 homodimer-DNA complex at 2.1 Å resolution. EMBO J 16:7078-7090 (Pubitemid 27520807)
16. Croy CH, Bergqvist S, Huxford T, Ghosh G, Komives EA (2004) Biophysical characterization of the free IκBα ankyrin repeat domain in solution. Protein Sci 13:1767-1777 (Pubitemid 38822116)
17. Dong J, Jimi E, Zhong H, Hayden MS, Ghosh S (2008) Repression of gene expression by unphosphorylated NF-κB p65 through epigenetic mechanisms. Genes Dev 22:1159-1173 (Pubitemid 351656576)
18. Ea CK, Baltimore D (2009) Regulation of NF-κB activity through lysine monomethylation of p65. Proc Natl Acad Sci USA 106:18972-18977
19. Escalante CR, Shen L, Thanos D, Aggarwal AK (2002) Structure of NF-κB p50/p65 heterodimer bound to the PRDII DNA element from the interferon-beta promoter. Structure 10:383-391 (Pubitemid 34230625)
20. Fenwick C, Na SY, Voll RE, Zhong H, Im SY, Lee JW, Ghosh S (2000) A subclass of Ras proteins that regulate the degradation of IκB. Science 287:869-873 (Pubitemid 30084332)
21. Ferreiro DU, Cervantes CF, Truhlar SM, Cho SS, Wolynes PG, Komives EA (2007) Stabilizing IκBalpha by "consensus" design. J Mol Biol 365:1201-1216
22. Fiorini E, Schmitz I, Marissen WE, Osborn SL, Touma M, Sasada T, Reche PA, Tibaldi EV, Hussey RE, Kruisbeek AM et al (2002) Peptide-induced negative selection of thymocytes activates transcription of an NF-κB inhibitor. Mol Cell 9:637-648 (Pubitemid 34273793)
23. Fusco AJ, Huang DB, Miller D, Wang VY, Vu D, Ghosh G (2009) NF-κB p52:RelB heterodimer recognizes two classes of κB sites with two distinct modes. EMBO Rep 10:152-159
24. Gaudet R (2008) A primer on ankyrin repeat function in TRP channels and beyond. Mol Biosyst 4:372-379 (Pubitemid 351552007)
25. Ghosh G, van Duyne G, Ghosh S, Sigler PB (1995) Structure of NF-κB p50 homodimer bound to a κB site. Nature 373:303-310
26. Ghosh S, May MJ, Kopp EB (1998) NF-κB and Rel proteins: evolutionarily conserved mediators of immune responses. Annu Rev Immunol 16:225-260 (Pubitemid 28183365)
27. Gilmore TD (2006) Introduction to NF-κB: players, pathways, perspectives. Oncogene 25:6680-6684 (Pubitemid 44657845)
28. Haruta H, Kato A, Todokoro K (2001) Isolation of a novel interleukin-1-inducible nuclear protein bearing ankyrin-repeat motifs. J Biol Chem 276:12485-12488
29. Hatada EN, Nieters A, Wulczyn FG, Naumann M, Meyer R, Nucifora G, McKeithan TW, Scheidereit C (1992) The ankyrin repeat domains of the NF-κB precursor p105 and the protooncogene bcl-3 act as specific inhibitors of NF-κB DNA binding. Proc Natl Acad Sci USA 89:2489-2493
30. Hatada EN, Naumann M, Scheidereit C (1993) Common structural constituents confer IκB activity to NF-κB p105 and IκB/MAD-3. EMBO J 12:2781-2788 (Pubitemid 23218327)
31. Hayden MS, Ghosh S (2008) Shared principles in NF-κB signaling. Cell 132:344-362
32. Hoffmann A, Levchenko A, Scott ML, Baltimore D (2002) The IκB-NF-κB signaling module: temporal control and selective gene activation. Science 298:1241-1245 (Pubitemid 35285493)
33. Huang DB, Huxford T, Chen YQ, Ghosh G (1997) The role of DNA in the mechanism of NF-κB dimer formation: crystal structures of the dimerization domains of the p50 and p65 subunits. Structure 5:1427-1436 (Pubitemid 27521799)
34. Huang DB, Chen YQ, Ruetsche M, Phelps CB, Ghosh G (2001) X-ray crystal structure of protooncogene product c-Rel bound to the CD28 response element of IL-2. Structure 9:669-678 (Pubitemid 32772889)
35. 2 complexed to a high-affinity RNA aptamer. Proc Natl Acad Sci USA 100:9268-9273 (Pubitemid 37033918)
36. Huang DB, Vu D, Ghosh G (2005) NF-κB RelB forms an intertwined homodimer. Structure 13:1365-1373 (Pubitemid 41262103)
37. Huxford T, Huang DB, Malek S, Ghosh G (1998) The crystal structure of the IκBα/NF-κB complex reveals mechanisms of NF-κB inactivation. Cell 95:759-770 (Pubitemid 29014456)
38. Ishikawa H, Carrasco D, Claudio E, Ryseck RP, Bravo R (1997) Gastric hyperplasia and increased proliferative responses of lymphocytes in mice lacking the COOH-terminal ankyrin domain of NF-κB2. J Exp Med 186:999-1014 (Pubitemid 27441145)
39. Ishikawa H, Claudio E, Dambach D, Raventos-Suarez C, Ryan C, Bravo R (1998) Chronic inflammation and susceptibility to bacterial infections in mice lacking the polypeptide (p) 105 precursor (NF-κB1) but expressing p50. J Exp Med 187:985-996 (Pubitemid 28176399)
40. Jacobs MD, Harrison SC (1998) Structure of an IκBα/NF- κB complex. Cell 95:749-758
41. Karin M, Ben-Neriah Y (2000) Phosphorylation meets ubiquitination: the control of NF-κB activity. Annu Rev Immunol 18:621-663 (Pubitemid 30365393)
42. Kearns JD, Hoffmann A (2009) Integrating computational and biochemical studies to explore mechanisms in NF-κB signaling. J Biol Chem 284:5439-5443
43. Kearns JD, Basak S, Werner SL, Huang CS, Hoffmann A (2006) IκBepsilon provides negative feedback to control NF-κB oscillations, signaling dynamics, and inflammatory gene expression. J Cell Biol 173:659-664 (Pubitemid 46165574)
44. Kitamura H, Kanehira K, Okita K, Morimatsu M, Saito M (2000) MAIL, a novel nuclear IκB protein that potentiates LPS-induced IL-6 production. FEBS Lett 485:53-56
45. Kohl A, Binz HK, Forrer P, Stumpp MT, Plückthun A, Grutter MG (2003) Designed to be stable: crystal structure of a consensus ankyrin repeat protein. Proc Natl Acad Sci USA 100:1700-1705 (Pubitemid 36254511)
46. Li Z, Nabel GJ (1997) A new member of the IκB protein family, IκBε, inhibits RelA (p65)-mediated NF-κB transcription. Mol Cell Biol 17:6184-6190 (Pubitemid 27411128)
47. Malek S, Huang DB, Huxford T, Ghosh S, Ghosh G (2003) X-ray crystal structure of an IκBβ:NF-κB p65 homodimer complex. J Biol Chem 278:23094-23100 (Pubitemid 36830375)
48. Mathes E, O'Dea EL, Hoffmann A, Ghosh G (2008) NF-κB dictates the degradation pathway of IκBα. EMBO J 27:1357-1367
49. Mercurio F, Didonato J, Rosette C, Karin M (1992) Molecular cloning and characterization of a novel Rel/NF-κB family member displaying structural and functional homology to NF-κB p50/p105. DNA Cell Biol 11:523-537
50. Moorthy AK, Huang DB, Wang VY, Vu D, Ghosh G (2007) X-ray structure of a NF-κB p50/RelB/DNA complex reveals assembly of multiple dimers on tandem κB sites. J Mol Biol 373:723-734 (Pubitemid 47488406)
51. Muenchen HJ, Lin DL, Walsh MA, Keller ET, Pienta KJ (2000) Tumor necrosis factor-alphainduced apoptosis in prostate cancer cells through inhibition of nuclear factor-κB by an IκBα "super-repressor". Clin Cancer Res 6:1969-1977 (Pubitemid 30305096)
52. Müller CW, Rey FA, Sodeoka M, Verdine GL, Harrison SC (1995) Structure of the NF-κB p50 homodimer bound to DNA. Nature 373:311-317
53. Naumann M, Nieters A, Hatada EN, Scheidereit C (1993) NF-κ B precursor p100 inhibits nuclear translocation and DNA binding of NF-κB/rel-factors. Oncogene 8:2275-2281 (Pubitemid 23226963)
54. Ohno H, Takimoto G, McKeithan TW (1990) The candidate proto-oncogene bcl-3 is related to genes implicated in cell lineage determination and cell cycle control. Cell 60:991-997
55. Pahl HL (1999) Activators and target genes of Rel/NF-κB transcription factors. Oncogene 18:6853-6866
56. Palmer S, Chen YH (2008) Bcl-3, a multifaceted modulator of NF-κB-mediated gene transcription. Immunol Res 42:210-218
57. Panne D, Maniatis T, Harrison SC (2007) An atomic model of the interferon-beta enhanceosome. Cell 129:1111-1123
58. Phelps CB, Ghosh G (2004) Discreet mutations from c-Rel to v-Rel alter κB DNA recognition, IκBα binding, and dimerization: implications for v-Rel oncogenicity. Oncogene 23:1229-1238 (Pubitemid 38297177)
59. Reber L, Vermeulen L, Haegeman G, Frossard N (2009) Ser276 phosphorylation of NF-κB p65 by MSK1 controls SCF expression in inflammation. PLoS One 4: e4393
60. Rice NR, MacKichan ML, Isräel A (1992) The precursor of NF-κB p50 has IκB-like functions. Cell 71:243-253
61. Rogers S, Wells R, Rechsteiner M (1986) Amino acid sequences common to rapidly degraded proteins: the PEST hypothesis. Science 234:364-368 (Pubitemid 17181385)
62. Savinova OV, Hoffmann A, Ghosh G (2009) The Nfkb1 and Nfkb2 proteins p105 and p100 function as the core of high-molecular-weight heterogeneous complexes. Mol Cell 34:591-602
63. Sen R, Baltimore D (1986) Multiple nuclear factors interact with the immunoglobulin enhancer sequences. Cell 46:705-716 (Pubitemid 16020062)
64. Senftleben U, Cao Y, Xiao G, Greten FR, Krahn G, Bonizzi G, Chen Y, Hu Y, Fong A, Sun SC, Karin M (2001) Activation by IKKα of a second, evolutionary conserved, NF-κB signaling pathway. Science 293:1495-1499 (Pubitemid 32801552)
65. Sengchanthalangsy LL, Datta S, Huang DB, Anderson E, Braswell EH, Ghosh G (1999) Characterization of the dimer interface of transcription factor NF-κB p50 homodimer. J Mol Biol 289:1029-1040 (Pubitemid 29306668)
66. Shih VF, Kearns JD, Basak S, Savinova OV, Ghosh G, Hoffmann A (2009) Kinetic control of negative feedback regulators of NF-κB/RelA determines their pathogen-and cytokinereceptor signaling specificity. Proc Natl Acad Sci USA 106:9619-9624
67. Simeonidis S, Liang S, Chen G, Thanos D (1997) Cloning and functional characterization of mouse IκBε. Proc Natl Acad Sci USA 94:14372-14377
68. Sriskantharajah S, Belich MP, Papoutsopoulou S, Janzen J, Tybulewicz V, Seddon B, Ley SC (2009) Proteolysis of NF-κB1 p105 is essential for T cell antigen receptor-induced proliferation. Nat Immunol 10:38-47
69. Tergaonkar V, Correa RG, Ikawa M, Verma IM (2005) Distinct roles of IκB proteins in regulating constitutive NF-κB activity. Nat Cell Biol 7:921-923 (Pubitemid 41486295)
70. Thompson JE, Phillips RJ, Erdjument-Bromage H, Tempst P, Ghosh S (1995) IκBβ regulates the persistent response in a biphasic activation of NF-κB. Cell 80:573-582
71. Touma M, Antonini V, Kumar M, Osborn SL, Bobenchik AM, Keskin DB, Connolly JE, Grusby MJ, Reinherz EL, Clayton LK (2007) Functional role for IκBNS in T cell cytokine regulation as revealed by targeted gene disruption. J Immunol 179:1681-1692
72. Truhlar SM, Mathes E, Cervantes CF, Ghosh G, Komives EA (2008) Pre-folding IκBα alters control of NF-κB signaling. J Mol Biol 380:67-82
73. Vermeulen L, De Wilde G, Van Damme P, Vanden Berghe W, Haegeman G (2003) Transcriptional activation of the NF-κB p65 subunit by mitogen-and stress-activated protein kinase-1 (MSK1). EMBO J 22:1313-1324 (Pubitemid 36362695)
74. Whiteside ST, Isräel A (1997) IκB proteins: structure, function and regulation. Semin Cancer Biol 8:75-82
75. Whiteside ST, Epinat JC, Rice NR, Isräel A (1997) IκBε, a novel member of the IκB family, controls RelA and cRel NF-κB activity. EMBO J 16:1413-1426 (Pubitemid 27136106)
76. Wu C, Ghosh S (2003) Differential phosphorylation of the signal-responsive domain of IκBα and IκBβ by IκB kinases. J Biol Chem 278:31980-31987 (Pubitemid 37048386)
77. Yamamoto M, Yamazaki S, Uematsu S, Sato S, Hemmi H, Hoshino K, Kaisho T, Kuwata H, Takeuchi O, Takeshige K et al (2004) Regulation of Toll/IL-1-receptor-mediated gene expression by the inducible nuclear protein IκBζ. Nature 430:218-222 (Pubitemid 38902431)
78. Yamazaki S, Muta T, Takeshige K (2001) A novel IκB protein, IκBζ, induced by proinflammatory stimuli, negatively regulates nuclear factor-κB in the nuclei. J Biol Chem 276:27657-27662
79. Yaron A, Hatzubai A, Davis M, Lavon I, Amit S, Manning AM, Andersen JS, Mann M, Mercurio F, Ben-Neriah Y (1998) Identification of the receptor component of the IκBα-ubiquitin ligase. Nature 396:590-594 (Pubitemid 28563722)
80. Zhong H, Voll RE, Ghosh S (1998) Phosphorylation of NF-κB p65 by PKA stimulates transcriptional activity by promoting a novel bivalent interaction with the coactivator CBP/p300. Mol Cell 1:661-671 (Pubitemid 128379244)