1932

Abstract

The innate immune system functions as the first line of defense against invading bacteria and viruses. In this context, the cGAS/STING [cyclic guanosine monophosphate (GMP)–adenosine monophosphate (AMP) synthase/STING] signaling axis perceives the nonself DNA associated with bacterial and viral infections, as well as the leakage of self DNA by cellular dysfunction and stresses, to elicit the host's immune responses. In this pathway, the noncanonical cyclic dinucleotide 2′,3′-cyclic GMP–AMP (2′,3′-cGAMP) functions as a second messenger for signal transduction: 2′,3′-cGAMP is produced by the enzyme cGAS upon its recognition of double-stranded DNA, and then the 2′,3′-cGAMP is recognized by the receptor STING to induce the phosphorylation of downstream factors, including TBK1 (TANK binding kinase 1) and IRF3 (interferon regulatory factor 3). Numerous crystal structures of the components of this cGAS/STING signaling axis have been reported and these clarify the structural basis for their signal transduction mechanisms. In this review, we summarize recent progress made in the structural dissection of this signaling pathway and indicate possible directions of forthcoming research.

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2017-06-20
2024-03-29
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Literature Cited

  1. Takeuchi O, Akira S. 1.  2010. Pattern recognition receptors and inflammation. Cell 140:6805–20 [Google Scholar]
  2. Pandey S, Kawai T, Akira S. 2.  2014. Microbial sensing by Toll-like receptors and intracellular nucleic acid sensors. Cold Spring Harb. Perspect. Biol. 7:1a016246 [Google Scholar]
  3. Wu J, Chen ZJ. 3.  2014. Innate immune sensing and signaling of cytosolic nucleic acids. Annu. Rev. Immunol. 32:461–88 [Google Scholar]
  4. Goubau D, Deddouche S, Reis e Sousa C. 4.  2013. Cytosolic sensing of viruses. Immunity 38:5855–69 [Google Scholar]
  5. O'Neill LA. 5.  2013. Sensing the dark side of DNA. Science 339:6121763–64 [Google Scholar]
  6. Barbalat R, Ewald SE, Mouchess ML, Barton GM. 6.  2011. Nucleic acid recognition by the innate immune system. Annu. Rev. Immunol. 29:185–214 [Google Scholar]
  7. Sun L, Wu J, Du F, Chen X, Chen ZJ. 7.  2013. Cyclic GMP–AMP synthase is a cytosolic DNA sensor that activates the type I interferon pathway. Science 339:6121786–91 [Google Scholar]
  8. Zhang X, Shi H, Wu J, Zhang X, Sun L. 8.  et al. 2013. Cyclic GMP–AMP containing mixed phosphodiester linkages is an endogenous high-affinity ligand for STING. Mol. Cell 51:2226–35 [Google Scholar]
  9. Ablasser A, Goldeck M, Cavlar T, Deimling T, Witte G. 9.  et al. 2013. cGAS produces a 2′-5′-linked cyclic dinucleotide second messenger that activates STING. Nature 498:7454380–84 [Google Scholar]
  10. Diner EJ, Burdette DL, Wilson SC, Monroe KM, Kellenberger CA. 10.  et al. 2013. The innate immune DNA sensor cGAS produces a noncanonical cyclic dinucleotide that activates human STING. Cell Rep 3:51355–61 [Google Scholar]
  11. Gao P, Ascano M, Wu Y, Barchet W, Gaffney BL. 11.  et al. 2013. Cyclic [G(2′,5′)pA(3′,5′)p] is the metazoan second messenger produced by DNA-activated cyclic GMP–AMP synthase. Cell 153:51094–107 [Google Scholar]
  12. Sun W, Li Y, Chen L, Chen H, You F. 12.  et al. 2009. ERIS, an endoplasmic reticulum IFN stimulator, activates innate immune signaling through dimerization. PNAS 106:218653–58 [Google Scholar]
  13. Zhong B, Yang Y, Li S, Wang Y-Y, Li Y. 13.  et al. 2008. The adaptor protein MITA links virus-sensing receptors to IRF3 transcription factor activation. Immunity 29:4538–50 [Google Scholar]
  14. Zhong B, Zhang L, Lei C, Li Y, Mao A-P. 14.  et al. 2009. The ubiquitin ligase RNF5 regulates antiviral responses by mediating degradation of the adaptor protein MITA. Immunity 30:3397–407 [Google Scholar]
  15. Jin L, Waterman PM, Jonscher KR, Short CM, Reisdorph NA, Cambier JC. 15.  2008. MPYS, a novel membrane tetraspanner, is associated with major histocompatibility complex class II and mediates transduction of apoptotic signals. Mol. Cell. Biol. 28:165014–26 [Google Scholar]
  16. Jin L, Lenz LL, Cambier JC. 16.  2010. Cellular reactive oxygen species inhibit MPYS induction of IFNβ.. PLOS ONE 5:12e15142 [Google Scholar]
  17. Jin L, Xu L-G, Yang IV, Davidson EJ, Schwartz DA. 17.  et al. 2011. Identification and characterization of a loss-of-function human MPYS variant. Genes Immun 12:4263–69 [Google Scholar]
  18. Jin L, Hill KK, Filak H, Mogan J, Knowles H. 18.  et al. 2011. MPYS is required for IFN response factor 3 activation and type I IFN production in the response of cultured phagocytes to bacterial second messengers cyclic-di-AMP and cyclic-di-GMP. J. Immunol. 187:52595–601 [Google Scholar]
  19. Choe C-H, Park IS, Park J, Yu K-Y, Jang H. 19.  et al. 2015. Transmembrane protein 173 inhibits RANKL-induced osteoclast differentiation. FEBS Lett 589:7836–41 [Google Scholar]
  20. Wu J, Sun L, Chen X, Du F, Shi H. 20.  et al. 2013. Cyclic GMP–AMP is an endogenous second messenger in innate immune signaling by cytosolic DNA. Science 339:6121826–30 [Google Scholar]
  21. Li X-D, Wu J, Gao D, Wang H, Sun L, Chen ZJ. 21.  2013. Pivotal roles of cGAS–cGAMP signaling in antiviral defense and immune adjuvant effects. Science 341:61521390–94 [Google Scholar]
  22. 22.  Deleted in proof
  23. Tanaka Y, Chen ZJ. 23.  2012. STING specifies IRF3 phosphorylation by TBK1 in the cytosolic DNA signaling pathway. Sci. Signal. 5:214ra20 [Google Scholar]
  24. Ishikawa H, Barber GN. 24.  2008. STING is an endoplasmic reticulum adaptor that facilitates innate immune signalling. Nature 455:7213674–78 [Google Scholar]
  25. McWhirter SM, Barbalat R, Monroe KM, Fontana MF, Hyodo M. 25.  et al. 2009. A host type I interferon response is induced by cytosolic sensing of the bacterial second messenger cyclic-di-GMP. J. Exp. Med. 206:91899–911 [Google Scholar]
  26. Kato K, Ishii R, Goto E, Ishitani R, Tokunaga F, Nureki O. 26.  2013. Structural and functional analyses of DNA-sensing and immune activation by human cGAS. PLOS ONE 8:10e76983 [Google Scholar]
  27. Chen H, Sun H, You F, Sun W, Zhou X. 27.  et al. 2011. Activation of STAT6 by STING is critical for antiviral innate immunity. Cell 147:2436–46 [Google Scholar]
  28. Lam E, Stein S, Falck-Pedersen E. 28.  2014. Adenovirus detection by the cGAS/STING/TBK1 DNA sensing cascade. J. Virol. 88:2974–81 [Google Scholar]
  29. Gao D, Wu J, Wu Y-T, Du F, Aroh C. 29.  et al. 2013. Cyclic GMP–AMP synthase is an innate immune sensor of HIV and other retroviruses. Science 341:6148903–6 [Google Scholar]
  30. Schoggins JW, MacDuff DA, Imanaka N, Gainey MD, Shrestha B. 30.  et al. 2014. Pan-viral specificity of IFN-induced genes reveals new roles for cGAS in innate immunity. Nature 505:7485691–95 [Google Scholar]
  31. Lahaye X, Satoh T, Gentili M, Cerboni S, Conrad C. 31.  et al. 2013. The capsids of HIV-1 and HIV-2 determine immune detection of the viral cDNA by the innate sensor cGAS in dendritic cells. Immunity 39:61132–42 [Google Scholar]
  32. Rasaiyaah J, Tan CP, Fletcher AJ, Price AJ, Blondeau C. 32.  et al. 2013. HIV-1 evades innate immune recognition through specific cofactor recruitment. Nature 503:7476402–5 [Google Scholar]
  33. Watson RO, Bell SL, MacDuff DA, Kimmey JM, Diner EJ. 33.  et al. 2015. The cytosolic sensor cGAS detects Mycobacterium tuberculosis DNA to induce type I interferons and activate autophagy. Cell Host Microbe 17:6811–19 [Google Scholar]
  34. Wassermann R, Gulen MF, Sala C, Perin SG, Lou Y. 34.  et al. 2015. Mycobacterium tuberculosis differentially activates cGAS- and inflammasome-dependent intracellular immune responses through ESX-1. Cell Host Microbe 17:6799–810 [Google Scholar]
  35. Collins AC, Cai H, Li T, Franco LH, Li X-D. 35.  et al. 2015. Cyclic GMP–AMP synthase is an innate immune DNA sensor for Mycobacterium tuberculosis. Cell Host Microbe 17:6820–28 [Google Scholar]
  36. Liang Q, Seo GJ, Choi YJ, Kwak M-J, Ge J. 36.  et al. 2014. Crosstalk between the cGAS DNA sensor and Beclin-1 autophagy protein shapes innate antimicrobial immune responses. Cell Host Microbe 15:2228–38 [Google Scholar]
  37. Fang C, Wei X, Wei Y. 37.  2016. Mitochondrial DNA in the regulation of innate immune responses. Protein Cell 7:111–16 [Google Scholar]
  38. West AP, Khoury-Hanold W, Staron M, Tal MC, Pineda CM. 38.  et al. 2015. Mitochondrial DNA stress primes the antiviral innate immune response. Nature 520:7548553–57 [Google Scholar]
  39. Rongvaux A, Jackson R, Harman CCD, Li T, West AP. 39.  et al. 2014. Apoptotic caspases prevent the induction of type I interferons by mitochondrial DNA. Cell 159:71563–77 [Google Scholar]
  40. White MJ, McArthur K, Metcalf D, Lane RM, Cambier JC. 40.  et al. 2014. Apoptotic caspases suppress mtDNA-induced STING-mediated type I IFN production. Cell 159:71549–62 [Google Scholar]
  41. Jeremiah N, Neven B, Gentili M, Callebaut I, Maschalidi S. 41.  et al. 2014. Inherited STING-activating mutation underlies a familial inflammatory syndrome with lupus-like manifestations. J. Clin. Investig. 124:125516–20 [Google Scholar]
  42. Gao D, Li T, Li X-D, Chen X, Li Q-Z. 42.  et al. 2015. Activation of cyclic GMP–AMP synthase by self-DNA causes autoimmune diseases. PNAS 112:42E5699–705 [Google Scholar]
  43. Gray EE, Treuting PM, Woodward JJ, Stetson DB. 43.  2015. Cutting edge: cGAS is required for lethal autoimmune disease in the Trex1-deficient mouse model of Aicardi-Goutières syndrome. J. Immunol. 195:51939–43 [Google Scholar]
  44. Deng L, Liang H, Xu M, Yang X, Burnette B. 44.  et al. 2014. STING-dependent cytosolic DNA sensing promotes radiation-induced type I interferon-dependent antitumor immunity in immunogenic tumors. Immunity 41:5843–52 [Google Scholar]
  45. Woo S-R, Fuertes MB, Corrales L, Spranger S, Furdyna MJ. 45.  et al. 2014. STING-dependent cytosolic DNA sensing mediates innate immune recognition of immunogenic tumors. Immunity 41:5830–42 [Google Scholar]
  46. Ahn J, Xia T, Konno H, Konno K, Ruiz P, Barber GN. 46.  2014. Inflammation-driven carcinogenesis is mediated through STING. Nat. Commun. 5:5166 [Google Scholar]
  47. Barber GN. 47.  2015. STING: infection, inflammation and cancer. Nat. Rev. Immunol. 15:12760–70 [Google Scholar]
  48. Burdette DL, Monroe KM, Sotelo-Troha K, Iwig JS, Eckert B. 48.  et al. 2011. STING is a direct innate immune sensor of cyclic di-GMP. Nature 478:7370515–18 [Google Scholar]
  49. Römling U, Galperin MY, Gomelsky M. 49.  2013. Cyclic di-GMP: the first 25 years of a universal bacterial second messenger. Microbiol. Mol. Biol. Rev. 77:11–52 [Google Scholar]
  50. Davies BW, Bogard RW, Young TS, Mekalanos JJ. 50.  2012. Coordinated regulation of accessory genetic elements produces cyclic di-nucleotides for V. cholerae virulence. Cell 149:2358–70 [Google Scholar]
  51. Gao P, Ascano M, Zillinger T, Wang W, Dai P. 51.  et al. 2013. Structure–function analysis of STING activation by c[G(2′,5′)pA(3′,5′)p] and targeting by antiviral DMXAA. Cell 154:4748–62 [Google Scholar]
  52. Civril F, Deimling T, de Oliveira Mann CC, Ablasser A, Moldt M. 52.  et al. 2013. Structural mechanism of cytosolic DNA sensing by cGAS. Nature 498:7454332–37 [Google Scholar]
  53. Zhang X, Wu J, Du F, Xu H, Sun L. 53.  et al. 2014. The cytosolic DNA sensor cGAS forms an oligomeric complex with DNA and undergoes switch-like conformational changes in the activation loop. Cell Rep 6:3421–30 [Google Scholar]
  54. Li X, Shu C, Yi G, Chaton CT, Shelton CL. 54.  et al. 2013. Cyclic GMP–AMP synthase is activated by double-stranded DNA-induced oligomerization. Immunity 39:61019–31 [Google Scholar]
  55. Kranzusch PJ, Lee AS, Berger JM, Doudna JA. 55.  2013. Structure of human cGAS reveals a conserved family of second-messenger enzymes in innate immunity. Cell Rep 3:51362–68 [Google Scholar]
  56. Mankan AK, Schmidt T, Chauhan D, Goldeck M, Höning K. 56.  et al. 2014. Cytosolic RNA:DNA hybrids activate the cGAS-STING axis. EMBO J 33:242937–46 [Google Scholar]
  57. Brody RS, Frey PA. 57.  1981. Unambiguous determination of the stereochemistry of nucleotidyl transfer catalyzed by DNA polymerase I from Escherichia coli. Biochemistry 20:51245–52 [Google Scholar]
  58. Steitz TA, Steitz JA. 58.  1993. A general two-metal-ion mechanism for catalytic RNA. PNAS 90:146498–502 [Google Scholar]
  59. Yang W, Lee JY, Nowotny M. 59.  2006. Making and breaking nucleic acids: two-Mg2+-ion catalysis and substrate specificity. Mol. Cell 22:15–13 [Google Scholar]
  60. Yin Q, Fu T-M, Li J, Wu H. 60.  2015. Structural biology of innate immunity. Annu. Rev. Immunol. 33:393–416 [Google Scholar]
  61. Huang Y-H, Liu X-Y, Du X-X, Jiang Z-F, Su X-D. 61.  2012. The structural basis for the sensing and binding of cyclic di-GMP by STING. Nat. Struct. Mol. Biol. 19:7728–30 [Google Scholar]
  62. Shang G, Zhu D, Li N, Zhang J, Zhu C. 62.  et al. 2012. Crystal structures of STING protein reveal basis for recognition of cyclic di-GMP. Nat. Struct. Mol. Biol. 19:7725–27 [Google Scholar]
  63. Shu C, Yi G, Watts T, Kao CC, Li P. 63.  2012. Structure of STING bound to cyclic di-GMP reveals the mechanism of cyclic dinucleotide recognition by the immune system. Nat. Struct. Mol. Biol. 19:7722–24 [Google Scholar]
  64. Ouyang S, Song X, Wang Y, Ru H, Shaw N. 64.  et al. 2012. Structural analysis of the STING adaptor protein reveals a hydrophobic dimer interface and mode of cyclic di-GMP binding. Immunity 36:61073–86 [Google Scholar]
  65. Yin Q, Tian Y, Kabaleeswaran V, Jiang X, Tu D. 65.  et al. 2012. Cyclic di-GMP sensing via the innate immune signaling protein STING. Mol. Cell 46:6735–45 [Google Scholar]
  66. Fukunaga R, Yokoyama S. 66.  2007. Structural insights into the second step of RNA-dependent cysteine biosynthesis in archaea: crystal structure of Sep-tRNA:Cys-tRNA synthase from Archaeoglobus fulgidus. J. Mol. Biol. 370:1128–41 [Google Scholar]
  67. Chin K-H, Tu Z-L, Su Y-C, Yu Y-J, Chen H-C. 67.  et al. 2013. Novel c-di-GMP recognition modes of the mouse innate immune adaptor protein STING. Acta Crystallogr. D 69:Pt 3352–66 [Google Scholar]
  68. Shi H, Wu J, Chen ZJ, Chen C. 68.  2015. Molecular basis for the specific recognition of the metazoan cyclic GMP–AMP by the innate immune adaptor protein STING. PNAS 112:298947–52 [Google Scholar]
  69. Liu S, Cai X, Wu J, Cong Q, Chen X. 69.  et al. 2015. Phosphorylation of innate immune adaptor proteins MAVS, STING, and TRIF induces IRF3 activation. Science 347:6227aaa2630 [Google Scholar]
  70. Zhao B, Shu C, Gao X, Sankaran B, Du F. 70.  et al. 2016. Structural basis for concerted recruitment and activation of IRF-3 by innate immune adaptor proteins. PNAS 113:24E3403–12 [Google Scholar]
  71. Taylor JL, Schoenherr CK, Grossberg SE. 71.  1980. High-yield interferon induction by 10-carboxymethyl-9-acridanone in mice and hamsters. Antimicrob. Agents Chemother. 18:120–26 [Google Scholar]
  72. Kramer MJ, Taylor JL, Grossberg SE. 72.  1981. Induction of interferon in mice by 10-carboxymethyl-9-acridanone. Methods Enzymol 78:Pt A284–87 [Google Scholar]
  73. Storch E, Kirchner H. 73.  1982. Induction of interferon in murine bone marrow-derived macrophage cultures by 10-carboxymethyl-9-acridanone. Eur. J. Immunol. 12:9793–96 [Google Scholar]
  74. Brehm G, Storch E, Kirchner H. 74.  1986. Characterization of interferon induced in murine macrophage cultures by 10-carboxymethyl-9-acridanone. Nat. Immun. Cell Growth Regul. 5:150–59 [Google Scholar]
  75. Storch E, Kirchner H, Brehm G, Hüller K, Marcucci F. 75.  1986. Production of interferon-β by murine T-cell lines induced by 10-carboxymethyl-9-acridanone. Scand. J. Immunol. 23:2195–99 [Google Scholar]
  76. Hornung RL, Young HA, Urba WJ, Wiltrout RH. 76.  1988. Immunomodulation of natural killer cell activity by flavone acetic acid: occurrence via induction of interferon α/β.. J. Natl. Cancer Inst. 80:151226–31 [Google Scholar]
  77. Futami H, Eader LA, Komschlies KL, Bull R, Gruys ME. 77.  et al. 1991. Flavone acetic acid directly induces expression of cytokine genes in mouse splenic leukocytes but not in human peripheral blood leukocytes. Cancer Res 51:246596–602 [Google Scholar]
  78. Perera P-Y, Barber SA, Ching L-M, Voge SN. 78.  1994. Activation of LPS-inducible genes by the antitumor agent 5,6-dimethylxanthenone-4-acetic acid in primary murine macrophages: dissection of signaling pathways leading to gene induction and tyrosine phosphorylation. J. Immunol. 153:104684–93 [Google Scholar]
  79. Baguley BC, Ching L-M. 79.  2002. DMXAA: an antivascular agent with multiple host responses. Int. J. Radiat. Oncol. Biol. Phys. 54:51503–11 [Google Scholar]
  80. Roberts ZJ, Goutagny N, Perera P-Y, Kato H, Kumar H. 80.  et al. 2007. The chemotherapeutic agent DMXAA potently and specifically activates the TBK1–IRF-3 signaling axis. J. Exp. Med. 204:71559–69 [Google Scholar]
  81. Prantner D, Perkins DJ, Lai W, Williams MS, Sharma S. 81.  et al. 2012. 5,6-dimethylxanthenone-4-acetic acid (DMXAA) activates stimulator of interferon gene (STING)-dependent innate immune pathways and is regulated by mitochondrial membrane potential. J. Biol. Chem. 287:4739776–88 [Google Scholar]
  82. Cavlar T, Deimling T, Ablasser A, Hopfner K-P, Hornung V. 82.  2013. Species-specific detection of the antiviral small-molecule compound CMA by STING. EMBO J 32:101440–50 [Google Scholar]
  83. Kim S, Li L, Maliga Z, Yin Q, Wu H. 83.  et al. 2013. Anticancer flavonoids are mouse-selective STING agonists. ACS Chem. Biol. 8:71396–401 [Google Scholar]
  84. Lara PN Jr., Douillard J-Y, Nakagawa K, von Pawel J, McKeage MJ. 84.  et al. 2011. Randomized phase III placebo-controlled trial of carboplatin and paclitaxel with or without the vascular disrupting agent vadimezan (ASA404) in advanced non-small-cell lung cancer. J. Clin. Oncol. 29:222965–71 [Google Scholar]
  85. Conlon J, Burdette DL, Sharma S, Bhat N, Thompson M. 85.  et al. 2013. Mouse, but not human STING, binds and signals in response to the vascular disrupting agent 5,6-dimethylxanthenone-4-acetic acid. J. Immunol. 190:105216–25 [Google Scholar]
  86. Gao P, Zillinger T, Wang W, Ascano M, Dai P. 86.  et al. 2014. Binding-pocket and lid-region substitutions render human STING sensitive to the species-specific drug DMXAA. Cell Rep 8:61668–76 [Google Scholar]
  87. Wu X, Wu F-H, Wang X, Wang L, Siedow JN. 87.  et al. 2014. Molecular evolutionary and structural analysis of the cytosolic DNA sensor cGAS and STING. Nucleic Acids Res 42:138243–57 [Google Scholar]
  88. Ross P, Weinhouse H, Aloni Y, Michaeli D, Weinberger-Ohana P. 88.  et al. 1987. Regulation of cellulose synthesis in Acetobacter xylinum by cyclic diguanylic acid. Nature 325:6101279–81 [Google Scholar]
  89. Römling U, Gomelsky M, Galperin MY. 89.  2005. c-di-GMP: the dawning of a novel bacterial signalling system. Mol. Microbiol. 57:3629–39 [Google Scholar]
  90. Hengge R. 90.  2009. Principles of c-di-GMP signalling in bacteria. Nat. Rev. Microbiol. 7:4263–73 [Google Scholar]
  91. Schirmer T, Jenal U. 91.  2009. Structural and mechanistic determinants of c-di-GMP signalling. Nat. Rev. Microbiol. 7:10724–35 [Google Scholar]
  92. Sondermann H, Shikuma NJ, Yildiz FH. 92.  2012. You've come a long way: c-di-GMP signaling. Curr. Opin. Microbiol. 15:2140–46 [Google Scholar]
  93. Zhu D, Wang L, Shang G, Liu X, Zhu J. 93.  et al. 2014. Structural biochemistry of a Vibrio cholerae dinucleotide cyclase reveals cyclase activity regulation by folates. Mol. Cell 55:6931–37 [Google Scholar]
  94. Kranzusch PJ, Lee ASY, Wilson SC, Solovykh MS, Vance RE, Berger JM. 94.  2014. Structure-guided reprogramming of human cGAS dinucleotide linkage specificity. Cell 158:51011–21 [Google Scholar]
  95. Kato K, Ishii R, Hirano S, Ishitani R, Nureki O. 95.  2015. Structural basis for the catalytic mechanism of DncV, bacterial homolog of cyclic GMP–AMP synthase. Structure 23:5843–50 [Google Scholar]
  96. Ming Z, Wang W, Xie Y, Ding P, Chen Y. 96.  et al. 2014. Crystal structure of the novel di-nucleotide cyclase from Vibrio cholerae (DncV) responsible for synthesizing a hybrid cyclic GMP–AMP. Cell Res 24:101270–73 [Google Scholar]
  97. Kranzusch PJ, Wilson SC, Lee ASY, Berger JM, Doudna JA, Vance RE. 97.  2015. Ancient origin of cGAS-STING reveals mechanism of universal 2′,3′ cGAMP signaling. Mol. Cell 59:6891–903 [Google Scholar]
  98. Wolenski FS, Garbati MR, Lubinski TJ, Traylor-Knowles N, Dresselhaus E. 98.  et al. 2011. Characterization of the core elements of the NF-κB signaling pathway of the sea anemone Nematostella vectensis. Mol. Cell. Biol. 31:51076–87 [Google Scholar]
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