KEGG PATHWAY: map04064

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

Reference

PMID:21772278

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

PMID:19203223

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

PMID:17183360

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

PMID:16264088

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

PMID:22017430

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

PMID:21173796

Authors

Sun SC

Title

Non-canonical NF-kappaB signaling pathway.

Journal

Cell Res 21:71-85 (2011)
DOI:10.1038/cr.2010.177

Reference

PMID:17431096

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

PMID:22119011

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

PMID:22017435

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

PMID:21232019

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

PMID:16984817

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

PMID:16356770

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

PMID:17098202

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

PMID:15134788

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

PMID:15905862

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

PMID:14657271

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

PMID:19726767

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

PMID:19302050

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

PMID:17047224

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

PMID:21872579

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

PMID:21187855

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

PMID:18832076

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

PMID:17607554

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

PMID:22390971

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

PMID:18613837

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

PMID:15546385

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

PMID:22152226

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

PMID:21135871

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

PMID:19489733

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

PMID:20300215

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

PMID:11875461

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

PMID:12654254

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

PMID:16251197

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

PMID:24070496

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

PMID:26260321

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

PMID:27508514

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

PMID:12787560

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

Reference

PMID:26646590

Authors

Hu Y, Ge W, Wang X, Sutendra G, Zhao K, Dedeic Z, Slee EA, Baer C, Lu X

Title

Caspase cleavage of iASPP potentiates its ability to inhibit p53 and NF-kappaB.

Journal

Oncotarget 6:42478-90 (2015)
DOI:10.18632/oncotarget.6478

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