Entry
Name
NF-kappa B signaling pathway - Homo sapiens (human)
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
BRITE hierarchy
Pathway map
Network
Element
N00151 TNF-NFKB signaling pathway
N00505 CD40-NFKB signaling pathway
N00559 LIGHT-HVEM-NFKB signaling pathway
N01797 EDA-EDAR signaling pathway
N01798 TNFSF11-TNFRSF11A signaling pathway
Drug
D00754 Thalidomide (JAN/USP/INN)
D04687 Lenalidomide (JAN/USAN/INN)
D09348 Fostamatinib disodium (USAN)
D09730 Olaparib (JAN/USAN/INN)
D09813 Lenalidomide hydrate (JAN)
D10733 Talazoparib tosylate (USAN)
D11209 Entospletinib (USAN/INN)
D11457 Fenebrutinib (USAN/INN)
D11790 Mivavotinib citrate (USAN)
D11873 Rilzabrutinib (JAN/USAN/INN)
D11907 Rozibafusp alfa (USAN/INN)
D12158 Elsubrutinib (USAN/INN)
D12160 Orelabrutinib (USAN/INN)
D12181 Edasalonexent (USAN/INN)
D12213 Tolebrutinib (JAN/USAN/INN)
D12285 Remibrutinib (JAN/USAN/INN)
D12352 Eclitasertib (USAN/INN)
D12383 Edralbrutinib (USAN/INN)
D12412 Emavusertib hydrochloride (USAN)
D12504 Nemtabrutinib (USAN/INN)
D12532 Emavusertib mesylate (USAN)
D12533 Emavusertib maleate (USAN)
D12538 Emavusertib phosphate (USAN)
D12539 emavusertib tosylate (USAN)
D12648 Quisovalimab (USAN/INN)
D12940 Oditrasertib (USAN/INN)
Organism
Homo sapiens (human) [GN:
hsa ]
Gene
10454 TAB1; TGF-beta activated kinase 1 (MAP3K7) binding protein 1 [KO:K04403 ]
10848 PPP1R13L; protein phosphatase 1 regulatory subunit 13 like [KO:K27356 ]
10892 MALT1; MALT1 paracaspase [KO:K07369 ] [EC:3.4.22.-]
10912 GADD45G; growth arrest and DNA damage inducible gamma [KO:K04402 ]
114609 TIRAP; TIR domain containing adaptor protein [KO:K05403 ]
1147 CHUK; component of inhibitor of nuclear factor kappa B kinase complex [KO:K04467 ] [EC:2.7.11.10 ]
115650 TNFRSF13C; TNF receptor superfamily member 13C [KO:K05151 ]
128178 EDARADD; EDAR associated via death domain [KO:K23324 ]
142 PARP1; poly(ADP-ribose) polymerase 1 [KO:K24070 ]
148022 TICAM1; TIR domain containing adaptor molecule 1 [KO:K05842 ]
1647 GADD45A; growth arrest and DNA damage inducible alpha [KO:K04402 ]
23085 ERC1; ELKS/RAB6-interacting/CAST family member 1 [KO:K16072 ]
23118 TAB2; TGF-beta activated kinase 1 (MAP3K7) binding protein 2 [KO:K04404 ]
257397 TAB3; TGF-beta activated kinase 1 (MAP3K7) binding protein 3 [KO:K12793 ]
27040 LAT; linker for activation of T cells [KO:K07362 ]
2919 CXCL1; C-X-C motif chemokine ligand 1 [KO:K05505 ]
2920 CXCL2; C-X-C motif chemokine ligand 2 [KO:K05505 ]
2921 CXCL3; C-X-C motif chemokine ligand 3 [KO:K05505 ]
29775 CARD10; caspase recruitment domain family member 10 [KO:K20912 ]
329 BIRC2; baculoviral IAP repeat containing 2 [KO:K16060 ]
330 BIRC3; baculoviral IAP repeat containing 3 [KO:K16060 ]
3383 ICAM1; intercellular adhesion molecule 1 [KO:K06490 ]
353376 TICAM2; TIR domain containing adaptor molecule 2 [KO:K05409 ]
3554 IL1R1; interleukin 1 receptor type 1 [KO:K04386 ]
3576 CXCL8; C-X-C motif chemokine ligand 8 [KO:K10030 ]
388372 CCL4L1; C-C motif chemokine ligand 4 like 1 [KO:K12964 ]
3929 LBP; lipopolysaccharide binding protein [KO:K05399 ]
4615 MYD88; MYD88 innate immune signal transduction adaptor [KO:K04729 ]
4616 GADD45B; growth arrest and DNA damage inducible beta [KO:K04402 ]
4790 NFKB1; nuclear factor kappa B subunit 1 [KO:K02580 ]
4791 NFKB2; nuclear factor kappa B subunit 2 [KO:K04469 ]
55367 PIDD1; p53-induced death domain protein 1 [KO:K10130 ]
596 BCL2; BCL2 apoptosis regulator [KO:K02161 ]
597 BCL2A1; BCL2 related protein A1 [KO:K02162 ]
5970 RELA; RELA proto-oncogene, NF-kB subunit [KO:K04735 ]
5971 RELB; RELB proto-oncogene, NF-kB subunit [KO:K09253 ]
6351 CCL4; C-C motif chemokine ligand 4 [KO:K12964 ]
6357 CCL13; C-C motif chemokine ligand 13 [KO:K16595 ]
6363 CCL19; C-C motif chemokine ligand 19 [KO:K05512 ]
6366 CCL21; C-C motif chemokine ligand 21 [KO:K16062 ]
6387 CXCL12; C-X-C motif chemokine ligand 12 [KO:K10031 ]
7132 TNFRSF1A; TNF receptor superfamily member 1A [KO:K03158 ]
7185 TRAF1; TNF receptor associated factor 1 [KO:K03172 ]
7187 TRAF3; TNF receptor associated factor 3 [KO:K03174 ]
7188 TRAF5; TNF receptor associated factor 5 [KO:K09849 ]
7329 UBE2I; ubiquitin conjugating enzyme E2 I [KO:K10577 ]
7412 VCAM1; vascular cell adhesion molecule 1 [KO:K06527 ]
7535 ZAP70; zeta chain of T cell receptor associated protein kinase 70 [KO:K07360 ] [EC:2.7.10.2 ]
79092 CARD14; caspase recruitment domain family member 14 [KO:K20913 ]
84433 CARD11; caspase recruitment domain family member 11 [KO:K07367 ]
8517 IKBKG; inhibitor of nuclear factor kappa B kinase regulatory subunit gamma [KO:K07210 ]
8600 TNFSF11; TNF superfamily member 11 [KO:K05473 ]
8717 TRADD; TNFRSF1A associated via death domain [KO:K03171 ]
8740 TNFSF14; TNF superfamily member 14 [KO:K05477 ]
8792 TNFRSF11A; TNF receptor superfamily member 11a [KO:K05147 ]
8837 CFLAR; CASP8 and FADD like apoptosis regulator [KO:K04724 ]
8915 BCL10; BCL10 immune signaling adaptor [KO:K07368 ]
9560 CCL4L2; C-C motif chemokine ligand 4 like 2 [KO:K12964 ]
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 pathway
hsa04060 Cytokine-cytokine receptor interaction
hsa04620 Toll-like receptor signaling pathway
hsa04622 RIG-I-like receptor signaling pathway
hsa04660 T cell receptor signaling pathway
hsa04662 B cell receptor signaling pathway
KO pathway