Signaling via the NFκB system

Wiley Interdisciplinary Reviews: Systems Biology and Medicine

Volumn 8, Issue 3, 2016, Pages 227-241

  Mitchell, Simon ^a   Vargas, Jesse ^a   Hoffmann, Alexander ^a  

^a UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CHAPERONE; I KAPPA B ALPHA; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; PROTEIN P100; PROTEIN P52; I KAPPA B KINASE;

DIMERIZATION; FEEDBACK SYSTEM; GENE EXPRESSION; NEGATIVE FEEDBACK; NONHUMAN; PROTEIN DEGRADATION; PROTEIN PROCESSING; PROTEIN SECRETION; REVIEW; SHEAR STRESS; SIGNAL TRANSDUCTION; ANIMAL; BIOLOGICAL MODEL; CHEMISTRY; GENETICS; HUMAN; INFLAMMATION; METABOLISM; NEOPLASM; OXIDATIVE STRESS; PATHOLOGY;

ANIMALS; DIMERIZATION; HUMANS; I-KAPPA B KINASE; INFLAMMATION; MODELS, BIOLOGICAL; NEOPLASMS; NF-KAPPA B; OXIDATIVE STRESS; PROTEIN PROCESSING, POST-TRANSLATIONAL; SIGNAL TRANSDUCTION;

EID: 84961275684     PISSN: 19395094     EISSN: 1939005X     Source Type: Journal    
DOI: 10.1002/wsbm.1331     Document Type: Review

References (122)

1. Hayden MS, Ghosh S . Signaling to NF-κB. Genes Dev 2004, 18:2195-2224.
2. Verstrepen L, Bekaert T, Chau TL, Tavernier J, Chariot A, Beyaert R . TLR-4, IL-1R and TNF-R signaling to NF-κB: variations on a common theme. Cell Mol Life Sci 2008, 65:2964-2978.
3. Gerondakis S, Grumont R, Gugasyan R, Wong L, Isomura I, Ho W, Banerjee A . Unravelling the complexities of the NF-κB signalling pathway using mouse knockout and transgenic models. Oncogene 2006, 25:6781-6799.
4. Vallabhapurapu S, Karin M . Regulation and function of NF-κB transcription factors in the immune system. Annu Rev Immunol 2009, 27:693-733.
5. Hayden MS, Ghosh S . NF-κB, the first quarter-century: remarkable progress and outstanding questions. Genes Dev 2012, 26:203-234.
6. Hoffmann A, Baltimore D . Circuitry of nuclear factor κB signaling. Immunol Rev 2006, 210:171-186.
7. Baud V, Karin M . Is NF-κB a good target for cancer therapy? Hopes and pitfalls. Nat Rev Drug Discov 2009, 8:33-40.
8. Cheong R, Hoffmann A, Levchenko A . Understanding NF-κB signaling via mathematical modeling. Mol Syst Biol 2008, 4:192.
9. Kearns JD, Hoffmann A . Integrating computational and biochemical studies to explore mechanisms in NF-κB signaling. J Biol Chem 2009, 284:5439-5443.
10. Basak S, Behar M, Hoffmann A . Lessons from mathematically modeling the NF-κB pathway. Immunol Rev 2012, 246:221-238.
11. O'Dea E, Hoffmann A . NF-κB signaling. WIREs Syst Biol Med 2009, 1:107-115.
12. O'Dea E, Hoffmann A . The regulatory logic of the NF-κB signaling system. Cold Spring Harb Perspect Biol 2010, 2:a000216.
13. Hoffmann A, Leung TH, Baltimore D . Genetic analysis of NF-κB/Rel transcription factors defines functional specificities. EMBO J 2003, 22:5530-5539.
14. Leung TH, Hoffmann A, Baltimore D . One nucleotide in a κB site can determine cofactor specificity for NF-κB dimers. Cell 2004, 118:453-464.
15. Sanjabi S, Hoffmann A, Liou HC, Baltimore D, Smale ST . Selective requirement for c-Rel during IL-12 P40 gene induction in macrophages. Proc Natl Acad Sci USA 2000, 97:12705-12710.
16. Sanjabi S, Williams KJ, Saccani S, Zhou L, Hoffmann A, Ghosh G, Gerondakis S, Natoli G, Smale ST . A c-Rel subdomain responsible for enhanced DNA-binding affinity and selective gene activation. Genes Dev 2005, 19:2138-2151.
17. Hoffmann A, Natoli G, Ghosh G . Transcriptional regulation via the NF-κB signaling module. Oncogene 2006, 25:6706-6716.
18. Shih VF, Tsui R, Caldwell A, Hoffmann A . A single NFκB system for both canonical and non-canonical signaling. Cell Res 2011, 21:86-102.
19. Mukherjee SP, Behar M, Birnbaum HA, Hoffmann A, Wright PE, Ghosh G . Analysis of the RelA:CBP/p300 interaction reveals its involvement in NF-κB-driven transcription. PLoS Biol 2013, 11:e1001647.
20. Ramirez-Carrozzi VR, Braas D, Bhatt DM, Cheng CS, Hong C, Doty KR, Black JC, Hoffmann A, Carey M, Smale ST . A unifying model for the selective regulation of inducible transcription by CpG islands and nucleosome remodeling. Cell 2009, 138:114-128.
21. Cheng CS, Feldman KE, Lee J, Verma S, Huang DB, Huynh K, Chang M, Ponomarenko JV, Sun SC, Benedict CA, et al. The specificity of innate immune responses is enforced by repression of interferon response elements by NF-κB p50. Sci Signal 2011, 4:ra11.
22. Huxford T, Hoffmann A, Ghosh G . Understanding the logic of IκB: NF-κB regulation in structural terms. In: NF-kB in Health and Disease. Berlin Heidelberg: Springer; 2011, 1-24.
23. Alves BN, Tsui R, Almaden J, Shokhirev MN, Davis-Turak J, Fujimoto J, Birnbaum H, Ponomarenko J, Hoffmann A . IκBε is a key regulator of B cell expansion by providing negative feedback on cRel and RelA in a stimulus-specific manner. J Immunol 2014, 192:3121-3132.
24. Escoubet-Lozach L, Benner C, Kaikkonen MU, Lozach J, Heinz S, Spann NJ, Crotti A, Stender J, Ghisletti S, Reichart D . Mechanisms establishing TLR4-responsive activation states of inflammatory response genes. PLoS Genet 2011, 7:e1002401.
25. Alkalay I, Yaron A, Hatzubai A, Orian A, Ciechanover A, Ben-Neriah Y . Stimulation-dependent Iκ B α phosphorylation marks the NF-κB inhibitor for degradation via the ubiquitin-proteasome pathway. Proc Natl Acad Sci USA 1995, 92:10599-10603.
26. Liu F, Xia Y, Parker AS, Verma IM . IKK biology. Immunol Rev 2012, 246:239-253.
27. Hoffmann A, Levchenko A, Scott ML, Baltimore D . The IκB-NF-κB signaling module: temporal control and selective gene activation. Science 2002, 298:1241-1245.
28. Basak S, Kim H, Kearns JD, Tergaonkar V, O'Dea E, Werner SL, Benedict CA, Ware CF, Ghosh G, Verma IM, et al. A fourth IκB protein within the NF-κB signaling module. Cell 2007, 128:369-381.
29. Iwai K . Diverse ubiquitin signaling in NF-κB activation. Trends Cell Biol 2012, 22:355-364.
30. Adhikari A, Xu M, Chen Z . Ubiquitin-mediated activation of TAK1 and IKK. Oncogene 2007, 26:3214-3226.
31. Cheong R, Bergmann A, Werner SL, Regal J, Hoffmann A, Levchenko A . Transient IκB kinase activity mediates temporal NF-κB dynamics in response to a wide range of tumor necrosis factor-α doses. J Biol Chem 2006, 281:2945-2950.
32. Shinohara H, Behar M, Inoue K, Hiroshima M, Yasuda T, Nagashima T, Kimura S, Sanjo H, Maeda S, Yumoto N, et al. Positive feedback within a kinase signaling complex functions as a switch mechanism for NF-κB activation. Science 2014, 344:760-764.
33. Niu J, Shi Y, Iwai K, Wu ZH . LUBAC regulates NF-κB activation upon genotoxic stress by promoting linear ubiquitination of NEMO. EMBO J 2011, 30:3741-3753.
34. Werner SL, Barken D, Hoffmann A . Stimulus specificity of gene expression programs determined by temporal control of IKK activity. Science 2005, 309:1857-1861.
35. Chen L-F, Greene WC . Shaping the nuclear action of NF-κB. Nat Rev Mol Cell Biol 2004, 5:392-401.
36. Schröfelbauer B, Polley S, Behar M, Ghosh G, Hoffmann A . NEMO ensures signaling specificity of the pleiotropic IKKβ by directing its kinase activity toward IκBα. Mol Cell 2012, 47:111-121.
37. Shih VF, Davis-Turak J, Macal M, Huang JQ, Ponomarenko J, Kearns JD, Yu T, Fagerlund R, Asagiri M, Zuniga EI . Control of RelB during dendritic cell activation integrates canonical and noncanonical NF-κB pathways. Nat Immunol 2012, 13:1162-1170.
38. Xu G, Lo Y-C, Li Q, Napolitano G, Wu X, Jiang X, Dreano M, Karin M, Wu H . Crystal structure of inhibitor of κB kinase β. Nature 2011, 472:325-330.
39. Polley S, Huang D-B, Hauenstein AV, Fusco AJ, Zhong X, Vu D, Schröfelbauer B, Kim Y, Hoffmann A, Verma IM . A structural basis for IκB kinase 2 activation via oligomerization-dependent trans auto-phosphorylation. PLoS Biol 2013, 11:e1001581.
40. Cheng Z, Taylor B, Ourthiague DR, Hoffmann A . Distinct single-cell signaling characteristics are conferred by the MyD88 and TRIF pathways during TLR4 activation. Sci Signal 2015, 8:ra69.
41. Behar M, Hoffmann A . Tunable signal processing through a kinase control cycle: the IKK signaling node. Biophys J 2013, 105:231-241.
42. Delhase M, Hayakawa M, Chen Y, Karin M . Positive and negative regulation of IκB kinase activity through IKKβ subunit phosphorylation. Science 1999, 284:309-313.
43. Schröfelbauer B, Hoffmann A . How do pleiotropic kinase hubs mediate specific signaling by TNFR superfamily members? Immunol Rev 2011, 244:29-43.
44. Werner SL, Kearns JD, Zadorozhnaya V, Lynch C, O'Dea E, Boldin MP, Ma A, Baltimore D, Hoffmann A . Encoding NF-κB temporal control in response to TNF: distinct roles for the negative regulators IκBα and A20. Genes Dev 2008, 22:2093-2101.
45. Mitchell S, Tsui R, Hoffmann A . Studying NF-κB signaling with mathematical models. Methods Mol Biol 2015, 1280:647-661.
46. Fagerlund R, Behar M, Fortmann KT, Lin YE, Vargas JD, Hoffmann A . Anatomy of a negative feedback loop: the case of IκBα. J R Soc Interface 2015, 12:0262.
47. Sachdev S, Hoffmann A, Hannink M . Nuclear localization of IκB α is mediated by the second ankyrin repeat: the IκB α ankyrin repeats define a novel class of cis-acting nuclear import sequences. Mol Cell Biol 1998, 18:2524-2534.
48. Mathes E, O'Dea EL, Hoffmann A, Ghosh G . NF-κB dictates the degradation pathway of IκBα. EMBO J 2008, 27:1357-1367.
49. O'Dea EL, Barken D, Peralta RQ, Tran KT, Werner SL, Kearns JD, Levchenko A, Hoffmann A . A homeostatic model of IκB metabolism to control constitutive NF-κB activity. Mol Syst Biol 2007, 3:111.
50. Fortmann KT, Lewis RD, Ngo KA, Fagerlund R, Hoffmann A . A regulated, ubiquitin-independent degron in IκBα. J Mol Biol 2015, 427:2748-2756.
51. Wuerzberger-Davis SM, Chen Y, Yang DT, Kearns JD, Bates PW, Lynch C, Ladell NC, Yu M, Podd A, Zeng H . Nuclear export of the NF-κB inhibitor IκBα is required for proper B cell and secondary lymphoid tissue formation. Immunity 2011, 34:188-200.
52. Mulero MC, Ferres-Marco D, Islam A, Margalef P, Pecoraro M, Toll A, Drechsel N, Charneco C, Davis S, Bellora N . Chromatin-bound IκBα regulates a subset of polycomb target genes in differentiation and cancer. Cancer Cell 2013, 24:151-166.
53. Bergqvist S, Alverdi V, Mengel B, Hoffmann A, Ghosh G, Komives EA . Kinetic enhancement of NF-κB·DNA dissociation by IκBα. Proc Natl Acad Sci USA 2009, 106:19328-19333.
54. Nelson D, Ihekwaba A, Elliott M, Johnson J, Gibney C, Foreman B, Nelson G, See V, Horton C, Spiller D . Oscillations in NF-κB signaling control the dynamics of gene expression. Science 2004, 306:704-708.
55. Regot S, Hughey JJ, Bajar BT, Carrasco S, Covert MW . High-sensitivity measurements of multiple kinase activities in live single cells. Cell 2014, 157:1724-1734.
56. Sung M-H, Bagain L, Chen Z, Karpova T, Yang X, Silvin C, Voss TC, McNally JG, Van Waes C, Hager GL . Dynamic effect of bortezomib on nuclear factor-κB activity and gene expression in tumor cells. Mol Pharmacol 2008, 74:1215-1222.
57. Kellogg RA, Tay S . Noise facilitates transcriptional control under dynamic inputs. Cell 2015, 160:381-392.
58. Selimkhanov J, Taylor B, Yao J, Pilko A, Albeck J, Hoffmann A, Tsimring L, Wollman R . Accurate information transmission through dynamic biochemical signaling networks. Science 2014, 346:1370-1373.
59. Behar M, Hoffmann A . Understanding the temporal codes of intra-cellular signals. Curr Opin Genet Dev 2010, 20:684-693.
60. Shih VF-S, Kearns JD, Basak S, Savinova OV, Ghosh G, Hoffmann A . Kinetic control of negative feedback regulators of NF-κB/RelA determines their pathogen-and cytokine-receptor signaling specificity. Proc Natl Acad Sci USA 2009, 106:9619-9624.
61. Savinova OV, Hoffmann A, Ghosh G . The Nfkb1 and Nfkb2 proteins p105 and p100 function as the core of high-molecular-weight heterogeneous complexes. Mol Cell 2009, 34:591-602.
62. Banoth B, Chatterjee B, Vijayaragavan B, Prasad MV, Roy P, Basak S . Stimulus-selective crosstalk via the NF-κB signaling system reinforces innate immune response to alleviate gut infection. Elife 2015, 4:eLife.05648.
63. Almaden JV, Tsui R, Liu YC, Birnbaum H, Shokhirev MN, Ngo KA, Davis-Turak JC, Otero D, Basak S, Rickert RC . A pathway switch directs BAFF signaling to distinct NFκB transcription factors in maturing and proliferating B cells. Cell Rep 2014, 9:2098-2111.
64. Longo DM, Selimkhanov J, Kearns JD, Hasty J, Hoffmann A, Tsimring LS . Dual delayed feedback provides sensitivity and robustness to the NF-κB signaling module. PLoS Comput Biol 2013, 9:e1003112.
65. Keams J, Basak S, Wemer S, Huang C, Hoffmann A . IκBε provides negative feedback to control NF-κB oscillations, signaling dynamics, and inflammatory gene expression. J Cell Biol 2006, 173:659-664.
66. Malek S, Chen Y, Huxford T, Ghosh G . IκBβ, but not IκBα, functions as a classical cytoplasmic inhibitor of NF-κB dimers by masking both NF-κB nuclear localization sequences in resting cells. J Biol Chem 2001, 276:45225-45235.
67. Caldwell AB, Cheng Z, Vargas JD, Birnbaum HA, Hoffmann A . Network dynamics determine the autocrine and paracrine signaling functions of TNF. Genes Dev 2014, 28:2120-2133.
68. Davis-Turak JC, Allison K, Shokhirev MN, Ponomarenko P, Tsimring LS, Glass CK, Johnson TL, Hoffmann A . Considering the kinetics of mRNA synthesis in the analysis of the genome and epigenome reveals determinants of co-transcriptional splicing. Nucleic Acids Res 2015, 43:699-707.
69. Coope H, Atkinson P, Huhse B, Belich M, Janzen J, Holman M, Klaus G, Johnston L, Ley S . CD40 regulates the processing of NF-κB2 p100 to p52. EMBO J 2002, 21:5375-5385.
70. Claudio E, Brown K, Park S, Wang H, Siebenlist U . BAFF-induced NEMO-independent processing of NF-κ B2 in maturing B cells. Nat Immunol 2002, 3:958-965.
71. Dejardin E, Droin NM, Delhase M, Haas E, Cao Y, Makris C, Li Z-W, Karin M, Ware CF, Green DR . The lymphotoxin-β receptor induces different patterns of gene expression via two NF-κB pathways. Immunity 2002, 17:525-535.
72. Kayagaki N, Yan M, Seshasayee D, Wang H, Lee W, French DM, Grewal IS, Cochran AG, Gordon NC, Yin J . BAFF/BLyS receptor 3 binds the B cell survival factor BAFF ligand through a discrete surface loop and promotes processing of NF-κB2. Immunity 2002, 17:515-524.
73. Novack DV, Yin L, Hagen-Stapleton A, Schreiber RD, Goeddel DV, Ross FP, Teitelbaum SL . The IκB function of NF-κB2 p100 controls stimulated osteoclastogenesis. J Exp Med 2003, 198:771-781.
74. Munroe ME, Bishop GA . Role of tumor necrosis factor (TNF) receptor-associated factor 2 (TRAF2) in distinct and overlapping CD40 and TNF receptor 2/CD120b-mediated B lymphocyte activation. J Biol Chem 2004, 279:53222-53231.
75. Saitoh T, Nakayama M, Nakano H, Yagita H, Yamamoto N, Yamaoka S . TWEAK induces NF-κB2 p100 processing and long lasting NF-κB activation. J Biol Chem 2003, 278:36005-36012.
76. Wicovsky A, Salzmann S, Roos C, Ehrenschwender M, Rosenthal T, Siegmund D, Henkler F, Gohlke F, Kneitz C, Wajant H . TNF-like weak inducer of apoptosis inhibits proinflammatory TNF receptor-1 signaling. Cell Death Differ 2009, 16:1445-1459.
77. Dejardin E . The alternative NF-κB pathway from biochemistry to biology: pitfalls and promises for future drug development. Biochem Pharmacol 2006, 72:1161-1179.
78. Bonizzi G, Bebien M, Otero DC, Johnson-Vroom KE, Cao Y, Vu D, Jegga AG, Aronow BJ, Ghosh G, Rickert RC, et al. Activation of IKKα target genes depends on recognition of specific κB binding sites by RelB:p52 dimers. EMBO J 2004, 23:4202-4210.
79. Wang VY-F, Huang W, Asagiri M, Spann N, Hoffmann A, Glass C, Ghosh G . The transcriptional specificity of NF-κB dimers is coded within the κB DNA response elements. Cell Rep 2012, 2:824-839.
80. Sun S-C . Non-canonical NF-κB signaling pathway. Cell Res 2011, 21:71-85.
81. Liao G, Zhang M, Harhaj EW, Sun S-C . Regulation of the NF-κB-inducing kinase by tumor necrosis factor receptor-associated factor 3-induced degradation. J Biol Chem 2004, 279:26243-26250.
82. He JQ, Zarnegar B, Oganesyan G, Saha SK, Yamazaki S, Doyle SE, Dempsey PW, Cheng G . Rescue of TRAF3-null mice by p100 NF-κB deficiency. J Exp Med 2006, 203:2413-2418.
83. Vallabhapurapu S, Matsuzawa A, Zhang W, Tseng P-H, Keats JJ, Wang H, Vignali DA, Bergsagel PL, Karin M . Nonredundant and complementary functions of TRAF2 and TRAF3 in a ubiquitination cascade that activates NIK-dependent alternative NF-κB signaling. Nat Immunol 2008, 9:1364-1370.
84. Xiao G, Harhaj EW, Sun S-C . NF-κB-inducing kinase regulates the processing of NF-κB2 p100. Mol Cell 2001, 7:401-409.
85. Senftleben U, Li Z-W, Baud V, Karin M . IKKβ is essential for protecting T cells from TNFα-induced apoptosis. Immunity 2001, 14:217-230.
86. Shinkura R, Kitada K, Matsuda F, Tashiro K, Ikuta K, Suzuki M, Kogishi K, Serikawa T, Honjo T . Alymphoplasia is caused by a point mutation in the mouse gene encoding NF-κB-inducing kinase. Nat Genet 1999, 22:74-77.
87. Ling L, Cao Z, Goeddel DV . NF-κB-inducing kinase activates IKK-α by phosphorylation of Ser-176. Proc Natl Acad Sci USA 1998, 95:3792-3797.
88. Lallena M-J, Diaz-Meco MT, Bren G, Payá CV, Moscat J . Activation of IκB kinase β by protein kinase C isoforms. Mol Cell Biol 1999, 19:2180-2188.
89. Lo JC, Basak S, James ES, Quiambo RS, Kinsella MC, Alegre ML, Weih F, Franzoso G, Hoffmann A, Fu YX . Coordination between NF-κB family members p50 and p52 is essential for mediating LTβR signals in the development and organization of secondary lymphoid tissues. Blood 2006, 107:1048-1055.
90. Mordmüller B, Krappmann D, Esen M, Wegener E, Scheidereit C . Lymphotoxin and lipopolysaccharide induce NF-κB-p52 generation by a co-translational mechanism. EMBO Rep 2003, 4:82-87.
91. Fusco AJ, Savinova OV, Talwar R, Kearns JD, Hoffmann A, Ghosh G . Stabilization of RelB requires multidomain interactions with p100/p52. J Biol Chem 2008, 283:12324-12332.
92. Basak S, Shih VF, Hoffmann A . Generation and activation of multiple dimeric transcription factors within the NF-κB signaling system. Mol Cell Biol 2008, 28:3139-3150.
93. Solan NJ, Miyoshi H, Carmona EM, Bren GD, Paya CV . RelB cellular regulation and transcriptional activity are regulated by p100. J Biol Chem 2002, 277:1405-1418.
94. Liao G, Sun S-C . Regulation of NF-κB2/p100 processing by its nuclear shuttling. Oncogene 2003, 22:4868-4874.
95. Busino L, Millman SE, Scotto L, Kyratsous CA, Basrur V, O'Connor O, Hoffmann A, Elenitoba-Johnson KS, Pagano M . Fbxw7α- and GSK3-mediated degradation of p100 is a pro-survival mechanism in multiple myeloma. Nat Cell Biol 2012, 14:375-385.
96. O'Dea EL, Kearns JD, Hoffmann A . UV as an amplifier rather than inducer of NF-κB activity. Mol Cell 2008, 30:632-641.
97. Tam AB, Mercado EL, Hoffmann A, Niwa M . ER stress activates NF-κB by integrating functions of basal IKK activity, IRE1 and PERK. PLoS One 2012, 7:e45078.
98. Mabb AM, Wuerzberger-Davis SM, Miyamoto S . PIASy mediates NEMO sumoylation and NF-κB activation in response to genotoxic stress. Nat Cell Biol 2006, 8:986-993.
99. Ho JQ, Asagiri M, Hoffmann A, Ghosh G . NF-κB potentiates caspase independent hydrogen peroxide induced cell death. PLoS One 2011, 6:e16815.
100. Huang TT, Wuerzberger-Davis SM, Wu Z-H, Miyamoto S . Sequential modification of NEMO/IKKγ by SUMO-1 and ubiquitin mediates NF-κB activation by genotoxic stress. Cell 2003, 115:565-576.
101. Chen NX, Geist DJ, Genetos DC, Pavalko FM, Duncan RL . Fluid shear-induced NFκB translocation in osteoblasts is mediated by intracellular calcium release. Bone 2003, 33:399-410.
102. Ganguli A, Persson L, Palmer IR, Evans I, Yang L, Smallwood R, Black R, Qwarnstrom EE . Distinct NF-κB regulation by shear stress through Ras-dependent IκBα oscillations: real-time analysis of flow-mediated activation in live cells. Circ Res 2005, 96:626-634.
103. Huang D-B, Vu D, Ghosh G . NF-κB RelB forms an intertwined homodimer. Structure 2005, 13:1365-1373.
104. Guo S, Liu M, Gonzalez-Perez RR . Role of Notch and its oncogenic signaling crosstalk in breast cancer. Biochim Biophys Acta 2011, 1815:197-213.
105. Tsui R, Kearns JD, Lynch C, Vu D, Ngo KA, Basak S, Ghosh G, Hoffmann A . IκBβ enhances the generation of the low-affinity NFκB/RelA homodimer. Nat Commun 2015, 6:7068.
106. Bren GD, Solan NJ, Miyoshi H, Pennington KN, Pobst LJ, Paya CV . Transcription of the RelB gene is regulated by NF-kB. Oncogene 2001, 20:7722-7733.
107. Sung M-H, Li N, Lao Q, Gottschalk RA, Hager GL, Fraser ID . Switching of the relative dominance between feedback mechanisms in lipopolysaccharide-induced NF-κB signaling. Sci Signal 2014, 7:ra6.
108. Beinke S, Ley S . Functions of NF-κB1 and NF-κB2 in immune cell biology. Biochem J 2004, 382:393-409.
109. Orian A, Gonen H, Bercovich B, Fajerman I, Eytan E, Israël A, Mercurio F, Iwai K, Schwartz AL, Ciechanover A . SCFβ-TrCP ubiquitin ligase-mediated processing of NF-κB p105 requires phosphorylation of its C-terminus by IκB kinase. EMBO J 2000, 19:2580-2591.
110. Basak S, Hoffmann A . Crosstalk via the NF-κB signaling system. Cytokine Growth Factor Rev 2008, 19:187-197.
111. Rao P, Hayden MS, Long M, Scott ML, West AP, Zhang D, Oeckinghaus A, Lynch C, Hoffmann A, Baltimore D, et al. IκBβ acts to inhibit and activate gene expression during the inflammatory response. Nature 2010, 466:1115-1119.
112. Saccani S, Marazzi I, Beg AA, Natoli G . Degradation of promoter-bound p65/RelA is essential for the prompt termination of the nuclear factor κB response. J Exp Med 2004, 200:107-113.
113. Lawrence T, Bebien M, Liu GY, Nizet V, Karin M . IKKα limits macrophage NF-κB activation and contributes to the resolution of inflammation. Nature 2005, 434:1138-1143.
114. Ryo A, Suizu F, Yoshida Y, Perrem K, Liou YC, Wulf G, Rottapel R, Yamaoka S, Lu KP . Regulation of NF-κB signaling by Pin1-dependent prolyl isomerization and ubiquitin-mediated proteolysis of p65/RelA. Mol Cell 2003, 12:1413-1426.
115. Mao X, Gluck N, Li D, Maine GN, Li H, Zaidi IW, Repaka A, Mayo MW, Burstein E . GCN5 is a required cofactor for a ubiquitin ligase that targets NF-κB/RelA. Genes Dev 2009, 23:849-861.
116. Mercurio F, DiDonato J, Rosette C, Karin M . p105 and p98 precursor proteins play an active role in NF-κB-mediated signal transduction. Genes Dev 1993, 7:705-718.
117. Liptay S, Schmid RM, Nabel EG, Nabel GJ . Transcriptional regulation of NF-κ B2: evidence for κ B-mediated positive and negative autoregulation. Mol Cell Biol 1994, 14:7695-7703.
118. Huang B, Yang XD, Lamb A, Chen LF . Posttranslational modifications of NF-κB: another layer of regulation for NF-κB signaling pathway. Cell Signal 2010, 22:1282-1290.
119. Lu T, Stark GR . NF-κB: regulation by methylation. Cancer Res 2015, 75:3692-3695.
120. Williams R, Timmis J, Qwarnstrom E . Computational models of the NF-KB signalling pathway. Computation 2014, 2:131.
121. Shokhirev MN, Almaden J, Davis-Turak J, Birnbaum HA, Russell TM, Vargas JA, Hoffmann A . A multi-scale approach reveals that NF-κB cRel enforces a B-cell decision to divide. Mol Syst Biol 2015, 11:783.
122. Fallahi-Sichani M, Kirschner DE, Linderman JJ . NF-κB signaling dynamics play a key role in infection control in tuberculosis. Front Physiol 2012, 3:170.