KEGG   PATHWAY: map04064
Entry
map04064                    Pathway                                

Name
NF-kappa B signaling pathway
Description
Nuclear factor-kappa B (NF-kappa B) is the generic name of a family of transcription factors that function as dimers and regulate genes involved in immunity, inflammation and cell survival. There are several pathways leading to NF-kappa B-activation. The canonical pathway is induced by tumour necrosis factor-alpha (TNF-alpha), interleukin-1 (IL-1) or byproducts of bacterial and viral infections. This pathway relies on IKK- mediated IkappaB-alpha phosphorylation on Ser32 and 36, leading to its degradation, which allows the p50/p65 NF-kappa B dimer to enter the nucleus and activate gene transcription. Atypical pathways are IKK-independent and rely on phosphorylation of IkappaB-alpha on Tyr42 or on Ser residues in IkappaB-alpha PEST domain. The non-canonical pathway is triggered by particular members of the TNFR superfamily, such as lymphotoxin-beta (LT-beta) or BAFF. It involves NIK and IKK-alpha-mediated p100 phosphorylation and processing to p52, resulting in nuclear translocation of p52/RelB heterodimers.
Class
Environmental Information Processing; Signal transduction
Pathway map
map04064  NF-kappa B signaling pathway
map04064

Disease
H01743  Autoinflammation and PLCG2-associated antibody deficiency and immune dysregulation
H02042  Familial expansile osteolysis
H02434  Diffuse large B-cell lymphoma, not otherwise specified
Reference
  Authors
Oeckinghaus A, Hayden MS, Ghosh S
  Title
Crosstalk in NF-kappaB signaling pathways.
  Journal
Nat Immunol 12:695-708 (2011)
DOI:10.1038/ni.2065
Reference
  Authors
Gloire G, Piette J
  Title
Redox regulation of nuclear post-translational modifications during NF-kappaB activation.
  Journal
Antioxid Redox Signal 11:2209-22 (2009)
DOI:10.1089/ARS.2009.2463
Reference
  Authors
Perkins ND
  Title
Integrating cell-signalling pathways with NF-kappaB and IKK function.
  Journal
Nat Rev Mol Cell Biol 8:49-62 (2007)
DOI:10.1038/nrm2083
Reference
  Authors
Lindstrom TM, Bennett PR
  Title
The role of nuclear factor kappa B in human labour.
  Journal
Reproduction 130:569-81 (2005)
DOI:10.1530/rep.1.00197
Reference
  Authors
Razani B, Reichardt AD, Cheng G
  Title
Non-canonical NF-kappaB signaling activation and regulation: principles and perspectives.
  Journal
Immunol Rev 244:44-54 (2011)
DOI:10.1111/j.1600-065X.2011.01059.x
Reference
  Authors
Sun SC
  Title
Non-canonical NF-kappaB signaling pathway.
  Journal
Cell Res 21:71-85 (2011)
DOI:10.1038/cr.2010.177
Reference
  Authors
Neumann M, Naumann M
  Title
Beyond IkappaBs: alternative regulation of NF-kappaB activity.
  Journal
FASEB J 21:2642-54 (2007)
DOI:10.1096/fj.06-7615rev
Reference
  Authors
Verhelst K, Carpentier I, Beyaert R
  Title
Regulation of TNF-induced NF-kappaB activation by different cytoplasmic ubiquitination events.
  Journal
Cytokine Growth Factor Rev 22:277-86 (2011)
DOI:10.1016/j.cytogfr.2011.11.002
Reference
  Authors
Rickert RC, Jellusova J, Miletic AV
  Title
Signaling by the tumor necrosis factor receptor superfamily in B-cell biology and disease.
  Journal
Immunol Rev 244:115-33 (2011)
DOI:10.1111/j.1600-065X.2011.01067.x
Reference
  Authors
Naude PJ, den Boer JA, Luiten PG, Eisel UL
  Title
Tumor necrosis factor receptor cross-talk.
  Journal
FEBS J 278:888-98 (2011)
DOI:10.1111/j.1742-4658.2011.08017.x
Reference
  Authors
Grivennikov SI, Kuprash DV, Liu ZG, Nedospasov SA
  Title
Intracellular signals and events activated by cytokines of the tumor necrosis factor superfamily: From simple paradigms to complex mechanisms.
  Journal
Int Rev Cytol 252:129-61 (2006)
DOI:10.1016/S0074-7696(06)52002-9
Reference
  Authors
Wada T, Nakashima T, Hiroshi N, Penninger JM
  Title
RANKL-RANK signaling in osteoclastogenesis and bone disease.
  Journal
Trends Mol Med 12:17-25 (2006)
DOI:10.1016/j.molmed.2005.11.007
Reference
  Authors
Schulze-Luehrmann J, Ghosh S
  Title
Antigen-receptor signaling to nuclear factor kappa B.
  Journal
Immunity 25:701-15 (2006)
DOI:10.1016/j.immuni.2006.10.010
Reference
  Authors
Weil R, Israel A
  Title
T-cell-receptor- and B-cell-receptor-mediated activation of NF-kappaB in lymphocytes.
  Journal
Curr Opin Immunol 16:374-81 (2004)
DOI:10.1016/j.coi.2004.03.003
Reference
  Authors
Siebenlist U, Brown K, Claudio E
  Title
Control of lymphocyte development by nuclear factor-kappaB.
  Journal
Nat Rev Immunol 5:435-45 (2005)
DOI:10.1038/nri1629
Reference
  Authors
Lucas PC, McAllister-Lucas LM, Nunez G
  Title
NF-kappaB signaling in lymphocytes: a new cast of characters.
  Journal
J Cell Sci 117:31-9 (2004)
DOI:10.1242/jcs.00904
Reference
  Authors
Khan WN
  Title
B cell receptor and BAFF receptor signaling regulation of B cell homeostasis.
  Journal
J Immunol 183:3561-7 (2009)
DOI:10.4049/jimmunol.0800933
Reference
  Authors
Vallabhapurapu S, Karin M
  Title
Regulation and function of NF-kappaB transcription factors in the immune system.
  Journal
Annu Rev Immunol 27:693-733 (2009)
DOI:10.1146/annurev.immunol.021908.132641
Reference
  Authors
Hacker H, Karin M
  Title
Regulation and function of IKK and IKK-related kinases.
  Journal
Sci STKE 2006:re13 (2006)
DOI:10.1126/stke.3572006re13
Reference
  Authors
Sabatel H, Pirlot C, Piette J, Habraken Y
  Title
Importance of PIKKs in NF-kappaB activation by genotoxic stress.
  Journal
Biochem Pharmacol 82:1371-83 (2011)
DOI:10.1016/j.bcp.2011.07.105
Reference
  Authors
Miyamoto S
  Title
Nuclear initiated NF-kappaB signaling: NEMO and ATM take center stage.
  Journal
Cell Res 21:116-30 (2011)
DOI:10.1038/cr.2010.179
Reference
  Authors
Brzoska K, Szumiel I
  Title
Signalling loops and linear pathways: NF-kappaB activation in response to genotoxic stress.
  Journal
Mutagenesis 24:1-8 (2009)
DOI:10.1093/mutage/gen056
Reference
  Authors
Wu ZH, Miyamoto S
  Title
Many faces of NF-kappaB signaling induced by genotoxic stress.
  Journal
J Mol Med (Berl) 85:1187-202 (2007)
DOI:10.1007/s00109-007-0227-9
Reference
  Authors
Maelfait J, Beyaert R
  Title
Emerging role of ubiquitination in antiviral RIG-I signaling.
  Journal
Microbiol Mol Biol Rev 76:33-45 (2012)
DOI:10.1128/MMBR.05012-11
Reference
  Authors
Ware CF
  Title
Targeting lymphocyte activation through the lymphotoxin and LIGHT pathways.
  Journal
Immunol Rev 223:186-201 (2008)
DOI:10.1111/j.1600-065X.2008.00629.x
Reference
  Authors
Schneider K, Potter KG, Ware CF
  Title
Lymphotoxin and LIGHT signaling pathways and target genes.
  Journal
Immunol Rev 202:49-66 (2004)
DOI:10.1111/j.0105-2896.2004.00206.x
Reference
  Authors
Remouchamps C, Boutaffala L, Ganeff C, Dejardin E
  Title
Biology and signal transduction pathways of the Lymphotoxin-alphabeta/LTbetaR system.
  Journal
Cytokine Growth Factor Rev 22:301-10 (2011)
DOI:10.1016/j.cytogfr.2011.11.007
Reference
  Authors
Liu S, Chen ZJ
  Title
Expanding role of ubiquitination in NF-kappaB signaling.
  Journal
Cell Res 21:6-21 (2011)
DOI:10.1038/cr.2010.170
Reference
  Authors
Skaug B, Jiang X, Chen ZJ
  Title
The role of ubiquitin in NF-kappaB regulatory pathways.
  Journal
Annu Rev Biochem 78:769-96 (2009)
DOI:10.1146/annurev.biochem.78.070907.102750
Reference
  Authors
Wertz IE, Dixit VM
  Title
Signaling to NF-kappaB: regulation by ubiquitination.
  Journal
Cold Spring Harb Perspect Biol 2:a003350 (2010)
DOI:10.1101/cshperspect.a003350
Reference
  Authors
Karin M, Lin A
  Title
NF-kappaB at the crossroads of life and death.
  Journal
Nat Immunol 3:221-7 (2002)
DOI:10.1038/ni0302-221
Reference
  Authors
Lin A, Karin M
  Title
NF-kappaB in cancer: a marked target.
  Journal
Semin Cancer Biol 13:107-14 (2003)
DOI:10.1016/S1044-579X(02)00128-1
Reference
  Authors
Morlon A, Munnich A, Smahi A
  Title
TAB2, TRAF6 and TAK1 are involved in NF-kappaB activation induced by the TNF-receptor, Edar and its adaptator Edaradd.
  Journal
Hum Mol Genet 14:3751-7 (2005)
DOI:10.1093/hmg/ddi405
Reference
  Authors
Sadier A, Viriot L, Pantalacci S, Laudet V
  Title
The ectodysplasin pathway: from diseases to adaptations.
  Journal
Trends Genet 30:24-31 (2014)
DOI:10.1016/j.tig.2013.08.006
Reference
  Authors
Verhelst K, Gardam S, Borghi A, Kreike M, Carpentier I, Beyaert R
  Title
XEDAR activates the non-canonical NF-kappaB pathway.
  Journal
Biochem Biophys Res Commun 465:275-80 (2015)
DOI:10.1016/j.bbrc.2015.08.019
Reference
  Authors
McDaniel DK, Eden K, Ringel VM, Allen IC
  Title
Emerging Roles for Noncanonical NF-kappaB Signaling in the Modulation of Inflammatory Bowel Disease Pathobiology.
  Journal
Inflamm Bowel Dis 22:2265-79 (2016)
DOI:10.1097/MIB.0000000000000858
Reference
  Authors
Mikkola ML, Thesleff I
  Title
Ectodysplasin signaling in development.
  Journal
Cytokine Growth Factor Rev 14:211-24 (2003)
DOI:10.1016/S1359-6101(03)00020-0
Related
pathway
map03050  Proteasome
map04020  Calcium signaling pathway
map04060  Cytokine-cytokine receptor interaction
map04120  Ubiquitin mediated proteolysis
map04210  Apoptosis
map04380  Osteoclast differentiation
map04620  Toll-like receptor signaling pathway
map04622  RIG-I-like receptor signaling pathway
map04660  T cell receptor signaling pathway
map04662  B cell receptor signaling pathway
KO pathway
ko04064   
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