Entry 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 transductionBRITE hierarchy
Pathway map ko04064 NF-kappa B signaling pathway
Orthology K01116 PLCG1; phosphatidylinositol phospholipase C, gamma-1 [EC:3.1.4.11 ]
K02161 BCL2; apoptosis regulator Bcl-2
K02162 BCL2A1; hematopoietic Bcl-2-related protein A1
K02580 NFKB1; nuclear factor NF-kappa-B p105 subunit
K02861 RIPK1, RIP1; receptor-interacting serine/threonine-protein kinase 1 [EC:2.7.11.1 ]
K03115 CSNK2B; casein kinase II subunit beta
K03156 TNF, TNFA; tumor necrosis factor superfamily, member 2
K03157 LTB, TNFC; lymphotoxin beta (TNF superfamily, member 3)
K03158 TNFRSF1A, TNFR1, CD120a; tumor necrosis factor receptor superfamily member 1A
K03159 TNFRSF3, LTBR; lymphotoxin beta receptor TNFR superfamily member 3
K03160 TNFRSF5, CD40; tumor necrosis factor receptor superfamily member 5
K03161 TNFSF5, CD40L, CD154; tumor necrosis factor ligand superfamily member 5
K03171 TRADD; tumor necrosis factor receptor type 1-associated DEATH domain protein
K03172 TRAF1; TNF receptor-associated factor 1
K03174 TRAF3; TNF receptor-associated factor 3
K04386 IL1R1, CD121a; interleukin 1 receptor type I
K04391 CD14; monocyte differentiation antigen CD14
K04402 GADD45; growth arrest and DNA-damage-inducible protein
K04403 MAP3K7IP1, TAB1; TAK1-binding protein 1
K04404 MAP3K7IP2, TAB2; TAK1-binding protein 2
K04427 MAP3K7, TAK1; mitogen-activated protein kinase kinase kinase 7 [EC:2.7.11.25 ]
K04466 MAP3K14, NIK; mitogen-activated protein kinase kinase kinase 14 [EC:2.7.11.25 ]
K04467 IKBKA, IKKA, CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha [EC:2.7.11.10 ]
K04469 NFKB2; nuclear factor of kappa light polypeptide gene enhancer in B-cells 2
K04519 IL1B; interleukin 1 beta
K04570 BCL2L1, bcl-xL; Bcl-2-like 1 (apoptosis regulator Bcl-X)
K04724 CFLAR, FLIP; CASP8 and FADD-like apoptosis regulator
K04729 MYD88; myeloid differentiation primary response protein MyD88
K04730 IRAK1; interleukin-1 receptor-associated kinase 1 [EC:2.7.11.1 ]
K04733 IRAK4; interleukin-1 receptor-associated kinase 4 [EC:2.7.11.1 ]
K04734 NFKBIA; NF-kappa-B inhibitor alpha
K04735 RELA; transcription factor p65
K05147 TNFRSF11A, RANK, CD265; tumor necrosis factor receptor superfamily member 11A
K05151 TNFRSF13C, BAFFR, CD268; tumor necrosis factor receptor superfamily member 13C
K05162 EDAR; tumor necrosis factor receptor superfamily member EDAR
K05163 EDA2R, TNFRSF27, XEDAR; tumor necrosis factor receptor superfamily member 27
K05399 LBP; lipopolysaccharide-binding protein
K05400 LY96, MD-2; lymphocyte antigen 96
K05403 TIRAP; toll-interleukin 1 receptor (TIR) domain-containing adaptor protein
K05409 TIRP, TRAM; TRIF-related adaptor molecule
K05468 LTA, TNFB; lymphotoxin alpha (TNF superfamily, member 1)
K05473 TNFSF11, RANKL, CD254; tumor necrosis factor ligand superfamily member 11
K05476 TNFSF13B, TNFSF20, CD257; tumor necrosis factor ligand superfamily member 13B
K05477 TNFSF14, LIGHT, CD258; tumor necrosis factor ligand superfamily member 14
K05505 CXCL1_2_3, GRO; C-X-C motif chemokine 1/2/3
K05512 CCL19, ELC; C-C motif chemokine 19
K05842 TRIF; toll-like receptor adapter molecule 1
K05856 LCK; lymphocyte cell-specific protein tyrosine kinase [EC:2.7.10.2 ]
K05859 PLCG2; phosphatidylinositol phospholipase C, gamma-2 [EC:3.1.4.11 ]
K06490 ICAM1, CD54; intercellular adhesion molecule 1
K06527 VCAM1, CD106; vascular cell adhesion molecule 1
K06856 IGH; immunoglobulin heavy chain
K07209 IKBKB, IKKB; inhibitor of nuclear factor kappa-B kinase subunit beta [EC:2.7.11.10 ]
K07210 IKBKG, IKKG, NEMO; inhibitor of nuclear factor kappa-B kinase subunit gamma
K07362 LAT; linker for activation of T cells family member 1
K07367 CARD11; caspase recruitment domain-containing protein 11
K07368 BCL10; B-cell CLL/lymphoma 10
K07369 MALT1; mucosa-associated lymphoid tissue lymphoma translocation protein 1 [EC:3.4.22.-]
K07371 BLNK; B-cell linker protein
K08601 CYLD, USLP2; ubiquitin carboxyl-terminal hydrolase CYLD [EC:3.4.19.12 ]
K09253 RELB; transcription factor RelB
K09849 TRAF5; TNF receptor-associated factor 5
K10030 IL8, CXCL8; interleukin 8
K10031 CXCL12; C-X-C motif chemokine 12
K10130 LRDD, PIDD; leucine-rich repeats and death domain-containing protein
K10160 TLR4, CD284; toll-like receptor 4
K10577 UBE2I, UBC9; ubiquitin-conjugating enzyme E2 I
K10652 TRIM25, EFP; tripartite motif-containing protein 25 [EC:2.3.2.27 ]
K10784 TRAV; T cell receptor alpha chain V region
K10785 TRBV; T-cell receptor beta chain V region
K11859 TNFAIP3, A20, OTUD7C; tumor necrosis factor, alpha-induced protein 3 [EC:3.4.19.12 ]
K12646 RIGI, DDX58; ATP-dependent RNA helicase DDX58 [EC:5.6.2.6 ]
K12793 MAP3K7IP3, TAB3; TAK1-binding protein 3
K12964 CCL4; C-C motif chemokine 4
K16060 BIRC2_3; baculoviral IAP repeat-containing protein 2/3
K16062 CCL21, SLC; C-C motif chemokine 21
K16072 ERC1, CAST2, ELKS; ELKS/RAB6-interacting/CAST family member 1
K16595 CCL13; C-C motif chemokine 13
K20912 CARD10; caspase recruitment domain-containing protein 10
K20913 CARD14; caspase recruitment domain-containing protein 14
K23324 EDARADD; ectodysplasin-A receptor-associated adapter protein
K24070 PARP1; poly [ADP-ribose] polymerase 1
K27356 PPP1R13L; RelA-associated inhibitor
Compound C01245 D-myo-Inositol 1,4,5-trisphosphate
Reference Authors Oeckinghaus A, Hayden MS, Ghosh S
Title Crosstalk in NF-kappaB signaling pathways.
Journal Reference Authors Gloire G, Piette J
Title Redox regulation of nuclear post-translational modifications during NF-kappaB activation.
Journal Reference Authors Perkins ND
Title Integrating cell-signalling pathways with NF-kappaB and IKK function.
Journal Reference Authors Lindstrom TM, Bennett PR
Title The role of nuclear factor kappa B in human labour.
Journal Reference Authors Razani B, Reichardt AD, Cheng G
Title Non-canonical NF-kappaB signaling activation and regulation: principles and perspectives.
Journal Reference Authors Sun SC
Title Non-canonical NF-kappaB signaling pathway.
Journal Reference Authors Neumann M, Naumann M
Title Beyond IkappaBs: alternative regulation of NF-kappaB activity.
Journal Reference Authors Verhelst K, Carpentier I, Beyaert R
Title Regulation of TNF-induced NF-kappaB activation by different cytoplasmic ubiquitination events.
Journal Reference Authors Rickert RC, Jellusova J, Miletic AV
Title Signaling by the tumor necrosis factor receptor superfamily in B-cell biology and disease.
Journal Reference Authors Naude PJ, den Boer JA, Luiten PG, Eisel UL
Title Tumor necrosis factor receptor cross-talk.
Journal 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 Reference Authors Wada T, Nakashima T, Hiroshi N, Penninger JM
Title RANKL-RANK signaling in osteoclastogenesis and bone disease.
Journal Reference Authors Schulze-Luehrmann J, Ghosh S
Title Antigen-receptor signaling to nuclear factor kappa B.
Journal Reference Authors Weil R, Israel A
Title T-cell-receptor- and B-cell-receptor-mediated activation of NF-kappaB in lymphocytes.
Journal Reference Authors Siebenlist U, Brown K, Claudio E
Title Control of lymphocyte development by nuclear factor-kappaB.
Journal Reference Authors Lucas PC, McAllister-Lucas LM, Nunez G
Title NF-kappaB signaling in lymphocytes: a new cast of characters.
Journal Reference Authors Khan WN
Title B cell receptor and BAFF receptor signaling regulation of B cell homeostasis.
Journal Reference Authors Vallabhapurapu S, Karin M
Title Regulation and function of NF-kappaB transcription factors in the immune system.
Journal Reference Authors Hacker H, Karin M
Title Regulation and function of IKK and IKK-related kinases.
Journal Reference Authors Sabatel H, Pirlot C, Piette J, Habraken Y
Title Importance of PIKKs in NF-kappaB activation by genotoxic stress.
Journal Reference Authors Miyamoto S
Title Nuclear initiated NF-kappaB signaling: NEMO and ATM take center stage.
Journal Reference Authors Brzoska K, Szumiel I
Title Signalling loops and linear pathways: NF-kappaB activation in response to genotoxic stress.
Journal Reference Authors Wu ZH, Miyamoto S
Title Many faces of NF-kappaB signaling induced by genotoxic stress.
Journal Reference Authors Maelfait J, Beyaert R
Title Emerging role of ubiquitination in antiviral RIG-I signaling.
Journal Reference Authors Ware CF
Title Targeting lymphocyte activation through the lymphotoxin and LIGHT pathways.
Journal Reference Authors Schneider K, Potter KG, Ware CF
Title Lymphotoxin and LIGHT signaling pathways and target genes.
Journal Reference Authors Remouchamps C, Boutaffala L, Ganeff C, Dejardin E
Title Biology and signal transduction pathways of the Lymphotoxin-alphabeta/LTbetaR system.
Journal Reference Authors Liu S, Chen ZJ
Title Expanding role of ubiquitination in NF-kappaB signaling.
Journal Reference Authors Skaug B, Jiang X, Chen ZJ
Title The role of ubiquitin in NF-kappaB regulatory pathways.
Journal Reference Authors Wertz IE, Dixit VM
Title Signaling to NF-kappaB: regulation by ubiquitination.
Journal Reference Authors Karin M, Lin A
Title NF-kappaB at the crossroads of life and death.
Journal Reference Authors Lin A, Karin M
Title NF-kappaB in cancer: a marked target.
Journal 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 Reference Authors Sadier A, Viriot L, Pantalacci S, Laudet V
Title The ectodysplasin pathway: from diseases to adaptations.
Journal Reference Authors Verhelst K, Gardam S, Borghi A, Kreike M, Carpentier I, Beyaert R
Title XEDAR activates the non-canonical NF-kappaB pathway.
Journal 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 Reference Authors Mikkola ML, Thesleff I
Title Ectodysplasin signaling in development.
Journal Reference 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 Related ko04060 Cytokine-cytokine receptor interaction
ko04120 Ubiquitin mediated proteolysis
ko04620 Toll-like receptor signaling pathway
ko04622 RIG-I-like receptor signaling pathway
ko04660 T cell receptor signaling pathway
ko04662 B cell receptor signaling pathway
