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Cited by 4,766NF-κB Signaling PathwaysImmune Response and InflammationSignaling Pathways in Disease

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Phosphorylation Meets Ubiquitination: The Control of NF-κB Activity

Karin, Michael, Ben-Neriah, Yinon·2000·Annual Review of Immunology
DOI 10.1146/annurev.immunol.18.1.621
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Abstract

NF-kappaB (nuclear factor-kappaB) is a collective name for inducible dimeric transcription factors composed of members of the Rel family of DNA-binding proteins that recognize a common sequence motif. NF-kappaB is found in essentially all cell types and is involved in activation of an exceptionally large number of genes in response to infections, inflammation, and other stressful situations requiring rapid reprogramming of gene expression. NF-kappaB is normally sequestered in the cytoplasm of nonstimulated cells and consequently must be translocated into the nucleus to function. The subcellular location of NF-kappaB is controlled by a family of inhibitory proteins, IkappaBs, which bind NF-kappaB and mask its nuclear localization signal, thereby preventing nuclear uptake. Exposure of cells to a variety of extracellular stimuli leads to the rapid phosphorylation, ubiquitination, and ultimately proteolytic degradation of IkappaB, which frees NF-kappaB to translocate to the nucleus where it regulates gene transcription. NF-kappaB activation represents a paradigm for controlling the function of a regulatory protein via ubiquitination-dependent proteolysis, as an integral part of a phosphorylationbased signaling cascade. Recently, considerable progress has been made in understanding the details of the signaling pathways that regulate NF-kappaB activity, particularly those responding to the proinflammatory cytokines tumor necrosis factor-alpha and interleukin-1. The multisubunit Ika…

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Research works printed but not linked: 229

  1. 10.1016/0092-8674(86)90807-X · DOI
  2. Baldwin AS. 1996. The NF-κB and IκB proteins: new discoveries and insights. Annu. Rev. Immunol. 14:649–81 · DOI
  3. Ghosh S, May MJ, Kopp EB. 1998. NFκB and Rel proteins: evolutionarily conserved mediators of immune responses. Annu. Rev. Immunol. 16:225–60 · DOI
  4. 10.1016/S0065-230X(08)60257-2 · DOI
  5. 10.1146/annurev.cb.10.110194.002201 · DOI
  6. 10.1006/scbi.1997.0060 · DOI
  7. Whiteside ST, Israël A. 1997. I κ B proteins: structure, function and regulation. Semin. Cancer Biol. 8:75–82 · DOI
  8. 1997, J. Cell Sci., 110, 369, 10.1242/jcs.110.3.369 · DOI
  9. 10.1128/MCB.16.5.2341 · DOI
  10. 10.1101/gad.9.22.2736 · DOI
  11. 10.1084/jem.188.6.1055 · DOI
  12. 10.1038/34356 · DOI
  13. 10.1038/nsb0198-67 · DOI
  14. 10.1038/373303a0 · DOI
  15. 10.1038/373311a0 · DOI
  16. 10.1016/S0092-8674(00)81699-2 · DOI
  17. 10.1016/S0092-8674(00)81698-0 · DOI
  18. 10.1016/S0065-2776(08)60742-7 · DOI
  19. 10.1056/NEJM199704103361506 · DOI
  20. 10.1146/annurev.biochem.67.1.227 · DOI · Paper page
  21. 10.1146/annurev.immunol.15.1.749 · DOI · Paper page
  22. 1995, Microbiol. Rev., 59, 481, 10.1128/mr.59.3.481-505.1995 · DOI
  23. 10.1006/meth.1998.0646 · DOI
  24. Baichwal VR, Baeuerle PA. 1997. Activate NF-κB or die? Curr. Biol. 7:R94–96 · DOI
  25. 10.1006/scbi.1997.0062 · DOI
  26. 1996, Oncogene, 13, 1367
  27. 10.1006/scbi.1997.0061 · DOI
  28. Grilli M, Memo M. 1999. NF-κB/Rel proteins: a point of convergence of signalling pathways relevant in neuronal function and dysfunction. Biochem. Pharmacol. 57:1–7 · DOI
  29. 10.1073/pnas.95.14.8211 · DOI
  30. 10.1183/09031936.98.12010221 · DOI
  31. 10.1136/gut.43.6.856 · DOI
  32. 10.1128/MCB.15.5.2809 · DOI
  33. 10.1126/science.7878466 · DOI · Paper page
  34. 10.1128/MCB.15.3.1302 · DOI · Paper page
  35. 10.1128/MCB.16.4.1295 · DOI · Paper page
  36. 10.1002/j.1460-2075.1995.tb07287.x · DOI
  37. 10.1128/MCB.15.10.5339 · DOI
  38. 10.1038/25159 · DOI
  39. 10.1016/S0092-8674(00)80752-7 · DOI
  40. 10.1101/gad.13.5.505 · DOI
  41. 10.1101/gad.9.13.1586 · DOI
  42. 10.1073/pnas.92.24.11259 · DOI
  43. 10.1074/jbc.271.1.376 · DOI
  44. 10.1073/pnas.92.23.10599 · DOI
  45. Lin Y-C, Brown K, Siebenlist U. 1995. Activation of NF-κB requires proteolysis of the inhibitor IκB: Signal-induced phosphorylation of IκB alone does not release active NF-κB. Proc. Natl. Acad. Sci. USA 92:3003–9 · DOI
  46. 10.1016/S0092-8674(00)80153-1 · DOI
  47. 10.1073/pnas.96.2.429 · DOI
  48. 10.1093/emboj/17.17.5170 · DOI
  49. 10.1073/pnas.95.22.13012 · DOI
  50. 10.1038/41493 · DOI · Paper page
  51. Mercurio F, Zhu H, Murray BW, Shevchenko A, Bennett BL, Li J, Young DB, Barbosa M, Mann M, Manning A, Rao A. 1997. IKK-1 and IKK-2: cytokineactivated IκB kinases essential for NFκB activation. Science 278:860–66 · DOI
  52. 10.1016/S0092-8674(00)81064-8 · DOI
  53. 10.1016/S0092-8674(00)81842-5 · DOI
  54. 10.1016/S0092-8674(00)80406-7 · DOI
  55. 10.1016/S0092-8674(00)80344-X · DOI
  56. 10.1126/science.278.5339.866 · DOI
  57. 1995, Cell. Mol. Biol. Res., 41, 537
  58. 10.1038/26261 · DOI
  59. 10.1016/S0092-8674(00)81466-X · DOI
  60. 10.1128/MCB.19.2.1526 · DOI
  61. 10.1073/pnas.96.3.1042 · DOI
  62. 1990, J. Immunol., 145, 3080, 10.4049/jimmunol.145.9.3080 · DOI
  63. 10.1038/26254 · DOI
  64. 10.1046/j.1432-1327.1999.00028.x · DOI
  65. 10.1016/S1097-2765(00)80179-3 · DOI
  66. Zandi E, Chen Y, Karin M. 1998. Direct phosphorylation of IκB by IKKα and IKKβ: discrimination between free and NF-κB-bound substrate. Science 281:1360–63 · DOI
  67. 10.1126/science.284.5412.321 · DOI
  68. 10.1084/jem.189.11.1839 · DOI
  69. 10.1016/S1074-7613(00)80042-4 · DOI
  70. 10.1074/jbc.274.22.15297 · DOI
  71. 10.1074/jbc.273.20.12041 · DOI
  72. 10.1074/jbc.273.46.30736 · DOI
  73. 10.1073/pnas.95.7.3792 · DOI
  74. 10.1126/science.284.5412.309 · DOI
  75. 10.1016/S0092-8674(00)81092-2 · DOI
  76. 10.1128/MCB.19.3.2180 · DOI
  77. 10.1128/MCB.18.10.5899 · DOI
  78. 10.1038/43474 · DOI · Paper page
  79. 10.1038/43466 · DOI · Paper page
  80. 10.1128/MCB.18.12.7336 · DOI
  81. 10.1073/pnas.95.16.9319 · DOI
  82. 10.1128/MCB.19.1.21 · DOI
  83. 10.1023/A:1021925629248 · DOI
  84. 10.1038/18465 · DOI
  85. 10.1074/jbc.274.15.10641 · DOI
  86. 10.1038/385540a0 · DOI
  87. Song HY, Régnier CH, Kirschning CJ, Goeddel DV, Rothe M. 1997. Tumor necrosis factor (TNF)-mediated kinase cascades: bifurcation of nuclear factorκB and c-jun N-terminal kinase (JNK/ SAPK) pathways at TNF receptor-associated factor 2. Proc. Natl. Acad. Sci. USA 94:9792–96 · DOI
  88. Baud V, Liu Z-G, Bennett B, Suzuki N, Xia Y, Karin M. 1999. Signaling by proinflammatory cytokines: oligomerization of TRAF2 and TRAF6 is sufficient for JNK and IKK activation and target gene induction via an N-terminal effector domain. Genes Dev. 13:1297– 308 · DOI
  89. 10.1126/science.284.5412.316 · DOI
  90. 10.1126/science.284.5412.313 · DOI
  91. 10.1038/8780 · DOI
  92. 10.1093/intimm/8.1.23 · DOI
  93. 10.1101/gad.12.21.3369 · DOI
  94. 10.1016/S1074-7613(00)80390-8 · DOI
  95. 10.1016/S1074-7613(00)80391-X · DOI
  96. 10.1073/pnas.95.5.2307 · DOI
  97. 10.1146/annurev.ge.29.120195.002103 · DOI
  98. 10.1101/gad.5.10.1892 · DOI
  99. 10.1016/0092-8674(91)90014-P · DOI
  100. 10.1038/ng0197-42 · DOI
  101. 10.1038/ng0197-36 · DOI
  102. 10.1038/376167a0 · DOI
  103. 10.1016/S1074-7613(00)80451-3 · DOI
  104. 10.1073/pnas.96.6.2994 · DOI
  105. Vandenabeele P, Declercg W, Beyaert R, Fiers W. 1995. Two tumour necrosis factor receptors: structure and function. Trends Cell. Biol. 5:392–99 · DOI · Paper page
  106. 10.1038/sj.onc.1202568 · DOI
  107. 10.1016/S0898-6568(98)00018-7 · DOI
  108. 10.1073/pnas.90.13.6155 · DOI
  109. Auron PE. 1998. The interleukin 1 receptor: ligand interactions and signal transduction. Cytokine Growth Factor Rev. 9:221–37 · DOI
  110. 10.1016/S1074-7613(00)80535-X · DOI · Paper page
  111. 10.1074/jbc.270.23.13757 · DOI
  112. Wesche H, Henzel WJ, Shillinglaw W, Li S, Cao Z. 1997. MyD88: an adapter that recruits IRAK to the IL-1 receptor complex. Immunity 7:837–47 · DOI
  113. Cao Z, Henzel WJ, Gao X. 1996. IRAK: a kinase associated with the interleukin1 receptor. Science 271:1128–31 · DOI
  114. 10.1126/science.278.5343.1612 · DOI
  115. 10.1038/383443a0 · DOI
  116. 10.1101/gad.12.18.2821 · DOI
  117. 10.1016/S1359-6101(98)00023-9 · DOI
  118. 10.1038/19110 · DOI
  119. 10.1126/science.7544915 · DOI
  120. Liu Z-G, Hu H, Goeddel DV, Karin M. 1996. Dissection of TNF receptor 1 effector functions: JNK activation is not linked to apoptosis, while NF-κB activation prevents cell death. Cell 87:565– 76 · DOI · Paper page
  121. Takeuchi M, Rothe M, Goeddel DV. 1996. Anatomy of TRAF2: distinct domains for nuclear factor-κB activation and association with tumor necrosis factor signaling proteins. J. Biol. Chem. 16:19935–42 · DOI
  122. 10.1074/jbc.271.25.14661 · DOI
  123. 10.1101/gad.13.8.1015 · DOI
  124. 10.1074/jbc.273.35.22681 · DOI
  125. 10.1074/jbc.272.51.32102 · DOI
  126. 10.1126/science.275.5296.90 · DOI
  127. 10.1016/S1097-2765(00)80283-X · DOI
  128. 10.1016/S0959-437X(96)80062-1 · DOI
  129. 10.1006/scbi.1997.0059 · DOI
  130. 10.1006/dbio.1996.0308 · DOI
  131. 10.1038/35154 · DOI · Paper page
  132. 10.1016/S0014-5793(99)00322-1 · DOI
  133. 10.1042/0264-6021:3390227 · DOI
  134. 10.1016/S0952-7915(99)80003-X · DOI
  135. 10.1126/science.284.5418.1313 · DOI
  136. 10.1038/32195 · DOI
  137. 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 93:10343–47 · DOI
  138. Baumeister W, Walz J, Zuhl F, Seemuller E. 1998. The proteasome: paradigm of a self-compartmentalizing protease. Cell 92:367–80 · DOI
  139. 10.1146/annurev.genet.30.1.405 · DOI
  140. 10.1146/annurev.biochem.67.1.425 · DOI · Paper page
  141. 10.1016/S0968-0004(97)01122-5 · DOI
  142. 10.1096/fasebj.11.14.9409544 · DOI
  143. 10.1016/0092-8674(93)90384-3 · DOI
  144. 10.1093/emboj/16.21.6325 · DOI · Paper page
  145. 10.1038/373081a0 · DOI
  146. 10.1038/10039 · DOI
  147. Zachariae W, Nosmyth K. 1999. Whose end is destruction: cell cycle division and the anaphase promoting complex. Genes Dev. 13:2039–58 · DOI
  148. Yamano H, Tsurumi C, Gannon J, Hunt T. 1998. The role of the destruction box and its neighbouring lysine residues in cyclin B for anaphase ubiquitin-dependent proteolysis in fission yeast: defining the D-box receptor. EMBO J. 17:5670– 78 · DOI
  149. 10.1016/S1097-2765(00)80126-4 · DOI
  150. 10.1016/S1097-2765(00)80286-5 · DOI
  151. Peters JM. 1998. SCF and APC: the yin and yang of cell cycle regulated proteolysis. Curr. Opin. Cell. Biol. 10:759–68 · DOI
  152. Patton EE, Willems AR, Tyers M. 1998. Combinatorial control in ubiquitindependent proteolysis: Don't Skp the Fbox hypothesis. Trends Genet. 14:236– 43 · DOI
  153. 10.1101/gad.13.12.1614 · DOI
  154. 10.1016/S1097-2765(00)80482-7 · DOI
  155. 10.1126/science.284.5414.657 · DOI
  156. 10.1038/20459 · DOI · Paper page
  157. 10.1128/MCB.18.2.732 · DOI
  158. 10.1126/science.284.5414.662 · DOI
  159. 10.1128/MCB.16.3.1058 · DOI
  160. 10.1093/emboj/16.21.6486 · DOI
  161. 10.1101/gad.7.7a.1266 · DOI
  162. 10.1002/j.1460-2075.1993.tb06157.x · DOI
  163. 10.1093/emboj/16.13.3797 · DOI
  164. 10.1126/science.275.5307.1790 · DOI
  165. 10.1126/science.275.5307.1787 · DOI
  166. 1998, Cancer Res., 58, 1344
  167. 10.1002/(SICI)1098-2264(199805)22:1<37::AID-GCC5>3.3.CO;2-P · DOI
  168. 1998, Cancer Res., 58, 2524
  169. 1998, Cancer Res., 58, 896
  170. 1998, Cancer Res., 58, 2520
  171. 1998, Cancer Res., 58, 1130
  172. 10.1073/pnas.95.15.8847 · DOI
  173. Spevak W, Keiper BD, Stratowa C, Castanon MJ. 1993. Saccharomyces cerevisiae cdc15 mutants arrested at a late stage in anaphase are rescued by Xenopus cDNAs encoding N-ras or a protein with beta-transducin repeats. Mol. Cell. Biol. 13:4953–66. Erratum. 1993. 13(11):7199 · DOI
  174. 10.1016/S1097-2765(00)80056-8 · DOI
  175. 10.1006/bbrc.1999.0289 · DOI
  176. 10.1073/pnas.96.7.3859 · DOI
  177. 10.1074/jbc.274.12.7941 · DOI
  178. 10.1101/gad.13.3.284 · DOI
  179. 10.1101/gad.13.21.2751 · DOI
  180. 10.1038/sj.onc.1202760 · DOI
  181. 10.1016/S0092-8674(00)81376-8 · DOI
  182. 1996, Nature, 379, 847
  183. 10.1038/360597a0 · DOI
  184. 10.1006/geno.1999.5792 · DOI
  185. 10.1016/S0960-9822(99)80091-8 · DOI
  186. 10.1093/emboj/18.9.2401 · DOI
  187. 10.1038/sj.onc.1202653 · DOI
  188. 10.1073/pnas.96.11.6273 · DOI
  189. 10.1016/S0925-4773(98)00134-8 · DOI
  190. 10.1016/S0304-419X(97)00008-5 · DOI
  191. 10.1016/S0165-4608(97)00479-2 · DOI
  192. 10.1002/(SICI)1098-2264(199808)22:4<295::AID-GCC5>3.3.CO;2-R · DOI
  193. 10.1038/sj.onc.1202073 · DOI
  194. 10.1126/science.274.5288.782 · DOI · Paper page
  195. Wang C-Y, Mayo MW, Baldwin AS Jr. 1996. TNF- and cancer therapy-induced apoptosis: potentiation by inhibition of NF-κB. Science 274:784–87 · DOI
  196. 10.1016/S0092-8674(00)81409-9 · DOI
  197. 10.1038/354395a0 · DOI
  198. 10.1016/S0092-8674(94)90482-0 · DOI
  199. Orian A, Whiteside S, Israël A, Stancovski I, Schwartz AL, Ciechanover A. 1995. Ubiquitin-mediated processing of NF-κB transcriptional activator precursor p105: reconstitution of a cell-free system and identification of the ubiquitin-carrier protein, E2, and a novel ubiquitin-protein ligase, E3, involved in conjugation. J. Biol. Chem. 270:21707– 14 · DOI
  200. 10.1074/jbc.273.15.8820 · DOI

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Metadata

Authors
Karin, M., & Ben-Neriah, Y.
Affiliations
  • Hebrew University of Jerusalem (IL)
  • Department of Pharmacology, Laboratory of Gene Regulation and Signal Transduction University of California, San Diego, La Jolla, California, 92093-0636;
ORCID
Karin, Michael
Venue
Annual Review of Immunology
Publisher
Annual Reviews
Published
2000-04
Volume
18
Issue
1
Pages
621-663
ISSN
  • 0732-0582 (ISSN-L)
  • 1545-3278
DOI
10.1146/annurev.immunol.18.1.621
OpenAlex
W2147921405
Cited by
4,766
References
243
Citations by year
2026: 78 · 2025: 109 · 2024: 86 · 2023: 101 · 2022: 114 · 2021: 112 · 2020: 129 · 2019: 114 · 2018: 129 · 2017: 153 · 2016: 156 · 2015: 135 · 2014: 186 · 2013: 201 · 2012: 194
FWCI
22.12
Type
journal article
Language
en
Open access
closed
Locations
  • Annual Review of Immunology (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Cancer Institute (R01 CA76188, R01CA076188)
  • National Institute of Allergy and Infectious Diseases (R01AI043477, R01 AI43477)
  • National Institute of Environmental Health Sciences (R37ES004151, R37 ES04151)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › NF-κB Signaling Pathways
  • Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Signaling Pathways in Disease
Keywords
NF-κB, IκB phosphorylation, ubiquitination, IκB kinase, IKKα, IKKβ, E3 ubiquitin ligase, proteolysis, NF-κB nuclear translocation, TNF signaling, IL-1 signaling, Rel family transcription factors, inflammation, transcriptional regulation
MeSH terms
NF-KappaB Inhibitor alpha, Amino Acid Sequence, Animals, DNA-Binding Proteins, Humans, Molecular Sequence Data, Phosphorylation, Transcription Factors, Ubiquitins, Signal Transduction, Down-Regulation, NF-kappa B, Protein Serine-Threonine Kinases, I-kappa B Proteins, I-kappa B Kinase, NF-kappa B p50 Subunit

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