_enti_e7
_enti_e102
_enti_e8
_enti_e104
_enti_e1
_enti_e9
_enti_e99
_enti_e105
_enti_e10
_enti_e103
_enti_e2
_enti_e4
_enti_e3
_enti_e98
_enti_e100
_enti_e101
_enti_e55
_enti_e83
_enti_e59
_enti_e53
_enti_e82
_enti_e81
_enti_e51
_enti_e52
_enti_e54
_enti_e56
_enti_e50
_enti_e85
_enti_e80
_enti_e84
_enti_e57
_enti_e61
_enti_e58
_enti_e60
_enti_e62
g2_fact_g2
g1_fact_g1
g1_fact_g14
g2_fact_g12
g2_fact_g13
g1_fact_g4
g1_fact_g5
g1_fact_g3
p1_propro_p1
PMID: 16982211
The binding of TNF to TNF receptor-1 (TNF-R1; the main receptor for soluble TNF on most cell types) (A) leads to the recruitment of TNF receptor-1 associated death domain protein (TRADD; red), which in turn recruits TNF receptor-associated factor 2 (TRAF2; orange) and receptor-interacting protein (RIP; dark grey).
c1 cso30:c:InputProcess connector
c2 cso30:c:InputProcess connector
c3 cso30:c:OutputProcess connector
p2_propro_p2
PMID: 16982211
The binding of TNF to TNF receptor-1 (TNF-R1; the main receptor for soluble TNF on most cell types) (A) leads to the recruitment of TNF receptor-1 associated death domain protein (TRADD; red), which in turn recruits TNF receptor-associated factor 2 (TRAF2; orange) and receptor-interacting protein (RIP; dark grey).
c4 cso30:c:InputProcess connector
c6 cso30:c:InputProcess connector
c5 cso30:c:OutputProcess connector
p3_propro_p3
PMID: 16982211
The binding of TNF to TNF receptor-1 (TNF-R1; the main receptor for soluble TNF on most cell types) (A) leads to the recruitment of TNF receptor-1 associated death domain protein (TRADD; red), which in turn recruits TNF receptor-associated factor 2 (TRAF2; orange) and receptor-interacting protein (RIP; dark grey).
c7 cso30:c:InputProcess connector
c8 cso30:c:InputProcess connector
c9 cso30:c:InputProcess connector
c10 cso30:c:OutputProcess connector
p4_propro_p4
PMID: 16982211
After its Ub ligase activity is turned on, TRAF2 catalyses K63 polyubiquitination of itself (A1).
c11 cso30:c:InputProcess connector
c12 cso30:c:OutputProcess connector
p5_propro_p5
PMID: 16982211
This causes the release of TRAF2 into the cytosol and TRAF2-mediated K63 polyubiqutination of RIP (A2).
c13 cso30:c:InputProcess connector
c15 cso30:c:OutputProcess connector
c14 cso30:c:OutputProcess connector
p6_propro_p6
PMID: 16982211
This causes the release of TRAF2 into the cytosol and TRAF2-mediated K63 polyubiqutination of RIP (A2).
c16 cso30:c:InputProcess connector
c17 cso30:c:OutputProcess connector
p7_propro_p7
PMID: 16982211
K63 polyubiquitinated RIP is recognized by the TAK1-binding proteins TAB2 and TAB3 (blue), as well as by IkappaB kinase gamma (IKKgamma; light green).
c18 cso30:c:InputProcess connector
c19 cso30:c:InputProcess connector
c20 cso30:c:InputProcess connector
c27 cso30:c:InputProcess connector
c21 cso30:c:OutputProcess connector
p8_propro_p8
PMID: 16982211
This brings the kinase TAK1 (light grey) in close proximity to the IKK complex, allowing it to phosphorylate the catalytic IKKalpha and IKKbeta subunits (pink; A3).
c22 cso30:c:InputProcess connector
c23 cso30:c:InputProcess connector
c24 cso30:c:OutputProcess connector
p9_propro_p9
PMID: 16982211
This brings the kinase TAK1 (light grey) in close proximity to the IKK complex, allowing it to phosphorylate the catalytic IKKalpha and IKKbeta subunits (pink; A3).
c25 cso30:c:InputProcess connector
c26 cso30:c:OutputProcess connector
p10_propro_p10
PMID: 16982211
The binding of IL-1beta to the IL-1 receptor (IL-1R)IL-1R accessory protein (IL-1RAcP) complex (B), or the binding of lipopolysaccharide (LPS) to the TLR4MD2CD14 complex (C), leads to the recruitment of myeloid differentiation factor 88 (MyD88; light yellow) and MyD88 adaptor-like (MAL), which subsequently recruit IL-1 receptor-associated kinase 1 (IRAK1; green), IRAK4 (purple) and TRAF6 (dark blue) to the receptor complex.
c28 cso30:c:InputProcess connector
c29 cso30:c:InputProcess connector
c30 cso30:c:OutputProcess connector
p11_propro_p11
PMID: 16982211
The binding of IL-1beta to the IL-1 receptor (IL-1R)IL-1R accessory protein (IL-1RAcP) complex (B), or the binding of lipopolysaccharide (LPS) to the TLR4MD2CD14 complex (C), leads to the recruitment of myeloid differentiation factor 88 (MyD88; light yellow) and MyD88 adaptor-like (MAL), which subsequently recruit IL-1 receptor-associated kinase 1 (IRAK1; green), IRAK4 (purple) and TRAF6 (dark blue) to the receptor complex.
c31 cso30:c:InputProcess connector
c33 cso30:c:InputProcess connector
c32 cso30:c:OutputProcess connector
p12_propro_p12
PMID: 16982211
The binding of IL-1beta to the IL-1 receptor (IL-1R)IL-1R accessory protein (IL-1RAcP) complex (B), or the binding of lipopolysaccharide (LPS) to the TLR4MD2CD14 complex (C), leads to the recruitment of myeloid differentiation factor 88 (MyD88; light yellow) and MyD88 adaptor-like (MAL), which subsequently recruit IL-1 receptor-associated kinase 1 (IRAK1; green), IRAK4 (purple) and TRAF6 (dark blue) to the receptor complex.
c34 cso30:c:InputProcess connector
c35 cso30:c:InputProcess connector
c36 cso30:c:OutputProcess connector
p13_propro_p13
PMID: 16982211
The binding of IL-1beta to the IL-1 receptor (IL-1R)IL-1R accessory protein (IL-1RAcP) complex (B), or the binding of lipopolysaccharide (LPS) to the TLR4MD2CD14 complex (C), leads to the recruitment of myeloid differentiation factor 88 (MyD88; light yellow) and MyD88 adaptor-like (MAL), which subsequently recruit IL-1 receptor-associated kinase 1 (IRAK1; green), IRAK4 (purple) and TRAF6 (dark blue) to the receptor complex.
c42 cso30:c:InputProcess connector
c37 cso30:c:InputProcess connector
c39 cso30:c:OutputProcess connector
p14_propro_p14
PMID: 16982211
The binding of IL-1beta to the IL-1 receptor (IL-1R)IL-1R accessory protein (IL-1RAcP) complex (B), or the binding of lipopolysaccharide (LPS) to the TLR4MD2CD14 complex (C), leads to the recruitment of myeloid differentiation factor 88 (MyD88; light yellow) and MyD88 adaptor-like (MAL), which subsequently recruit IL-1 receptor-associated kinase 1 (IRAK1; green), IRAK4 (purple) and TRAF6 (dark blue) to the receptor complex.
c40 cso30:c:InputProcess connector
c60 cso30:c:InputProcess connector
c41 cso30:c:OutputProcess connector
p15_propro_p15
PMID: 16982211
The binding of IL-1beta to the IL-1 receptor (IL-1R)IL-1R accessory protein (IL-1RAcP) complex (B), or the binding of lipopolysaccharide (LPS) to the TLR4MD2CD14 complex (C), leads to the recruitment of myeloid differentiation factor 88 (MyD88; light yellow) and MyD88 adaptor-like (MAL), which subsequently recruit IL-1 receptor-associated kinase 1 (IRAK1; green), IRAK4 (purple) and TRAF6 (dark blue) to the receptor complex.
c38 cso30:c:InputProcess connector
c43 cso30:c:InputProcess connector
c44 cso30:c:InputProcess connector
c45 cso30:c:OutputProcess connector
p16_propro_p16
PMID: 16982211
The binding of IL-1beta to the IL-1 receptor (IL-1R)IL-1R accessory protein (IL-1RAcP) complex (B), or the binding of lipopolysaccharide (LPS) to the TLR4MD2CD14 complex (C), leads to the recruitment of myeloid differentiation factor 88 (MyD88; light yellow) and MyD88 adaptor-like (MAL), which subsequently recruit IL-1 receptor-associated kinase 1 (IRAK1; green), IRAK4 (purple) and TRAF6 (dark blue) to the receptor complex.
c46 cso30:c:InputProcess connector
c48 cso30:c:InputProcess connector
c47 cso30:c:OutputProcess connector
p17_propro_p17
PMID: 16982211
The binding of IL-1beta to the IL-1 receptor (IL-1R)IL-1R accessory protein (IL-1RAcP) complex (B), or the binding of lipopolysaccharide (LPS) to the TLR4MD2CD14 complex (C), leads to the recruitment of myeloid differentiation factor 88 (MyD88; light yellow) and MyD88 adaptor-like (MAL), which subsequently recruit IL-1 receptor-associated kinase 1 (IRAK1; green), IRAK4 (purple) and TRAF6 (dark blue) to the receptor complex.
c49 cso30:c:InputProcess connector
c50 cso30:c:InputProcess connector
c258 cso30:c:InputProcess connector
c52 cso30:c:OutputProcess connector
p18_propro_p18
PMID: 16982211
The binding of IL-1beta to the IL-1 receptor (IL-1R)IL-1R accessory protein (IL-1RAcP) complex (B), or the binding of lipopolysaccharide (LPS) to the TLR4MD2CD14 complex (C), leads to the recruitment of myeloid differentiation factor 88 (MyD88; light yellow) and MyD88 adaptor-like (MAL), which subsequently recruit IL-1 receptor-associated kinase 1 (IRAK1; green), IRAK4 (purple) and TRAF6 (dark blue) to the receptor complex.
c53 cso30:c:InputProcess connector
c54 cso30:c:InputProcess connector
c55 cso30:c:OutputProcess connector
p19_propro_p19
PMID: 16982211
The phosphorylation of IRAK1 by IRAK4 (B1, C1) leads to the hyperphosphorylation of IRAK1 (B2, C2), followed by the dissociation of the IRAK1TRAF6 complex from the receptor.
c56 cso30:c:InputProcess connector
c57 cso30:c:OutputProcess connector
p20_propro_p20
PMID: 16982211
The phosphorylation of IRAK1 by IRAK4 (B1, C1) leads to the hyperphosphorylation of IRAK1 (B2, C2), followed by the dissociation of the IRAK1TRAF6 complex from the receptor.
c58 cso30:c:InputProcess connector
c59 cso30:c:OutputProcess connector
p21_propro_p21
PMID: 16982211
The phosphorylation of IRAK1 by IRAK4 (B1, C1) leads to the hyperphosphorylation of IRAK1 (B2, C2), followed by the dissociation of the IRAK1TRAF6 complex from the receptor.
c64 cso30:c:InputProcess connector
c65 cso30:c:OutputProcess connector
c66 cso30:c:OutputProcess connector
p22_propro_p22
PMID: 16982211
The phosphorylation of IRAK1 by IRAK4 (B1, C1) leads to the hyperphosphorylation of IRAK1 (B2, C2), followed by the dissociation of the IRAK1TRAF6 complex from the receptor.
c61 cso30:c:InputProcess connector
c62 cso30:c:OutputProcess connector
c63 cso30:c:OutputProcess connector
p23_propro_p23
PMID: 16982211
Once released from the receptor, the Ub-ligase activity of TRAF6 mediates its K63 auto-polyubiquitination (BC3).
PMID: 16982211, 16543409
This is further supported by the finding that overexpression of SOCS3 inhibits IL-1-induced NF-kappaB activation and co-immunoprecipitates with the TRAF6TAK1 complex.
c67 cso30:c:InputProcess connector
c252 cso30:c:InputInhibitor connector
c68 cso30:c:OutputProcess connector
p24_propro_p24
PMID: 16982211
K63-polyubiquitinated TRAF6 then recruits the TAK1TAB2TAB3 complex, which subsequently phosphorylates and activates IKKalpha and IKKbeta (BC4).
c69 cso30:c:InputProcess connector
c70 cso30:c:InputProcess connector
c71 cso30:c:OutputProcess connector
p25_propro_p25
PMID: 16982211
K63-polyubiquitinated TRAF6 then recruits the TAK1TAB2TAB3 complex, which subsequently phosphorylates and activates IKKalpha and IKKbeta (BC4).
c72 cso30:c:InputProcess connector
c74 cso30:c:InputAssociation connector
c255 cso30:c:InputAssociation connector
c73 cso30:c:OutputProcess connector
p26_propro_p26
PMID: 16982211
The IKKbeta catalytic subunit then phosphorylates the inhibitor of kappaB (IkappaB)α protein (D1), which keeps NF-kappaB (shown here as a p65p50 dimer) in the cytoplasm of resting cells.
c75 cso30:c:InputProcess connector
c77 cso30:c:InputAssociation connector
c76 cso30:c:OutputProcess connector
p27_propro_p27
PMID: 16982211
IkappaBalpha phosphorylation leads to its K48 polyubiquitination (D2) and subsequent proteasomal degradation (D3).
c78 cso30:c:InputProcess connector
c79 cso30:c:OutputProcess connector
p28_propro_p28
PMID: 16982211
IkappaBalpha phosphorylation leads to its K48 polyubiquitination (D2) and subsequent proteasomal degradation (D3).
PMID: 16982211, 16214042
Recently, ubiquitin specific peptidase 31 (USP31) was identified as another TRAF2 binding DUB that inhibits TNF-induced NF-kappaB activation upon overexpression.
PMID: 16982211, 8557994, 11463333, 16204640
Interestingly, overexpression of these genes was shown to inhibit TNF-induced and IL-1-induced NF-kappaB activation.
PMID: 16982211, 16543409
This is further supported by the finding that overexpression of SOCS3 inhibits IL-1-induced NF-kappaB activation and co-immunoprecipitates with the TRAF6TAK1 complex.
c80 cso30:c:InputProcess connector
c171 cso30:c:InputInhibitor connector
c221 cso30:c:InputInhibitor connector
c222 cso30:c:InputInhibitor connector
c223 cso30:c:InputInhibitor connector
c224 cso30:c:InputInhibitor connector
c225 cso30:c:InputInhibitor connector
c257 cso30:c:InputInhibitor connector
c82 cso30:c:OutputProcess connector
c81 cso30:c:OutputProcess connector
p29_propro_p29
PMID: 16982211
This allows NF-kappaB to translocate to the nucleus (D4), where it induces the transcription of genes with an NF-kappaB consensus site in their promoter region, including IkappaBalpha.
c83 cso30:c:InputProcess connector
c84 cso30:c:OutputProcess connector
p31_propro_p31
PMID: 16982211
This allows NF-kappaB to translocate to the nucleus (D4), where it induces the transcription of genes with an NF-kappaB consensus site in their promoter region, including IkappaBalpha.
c85 cso30:c:InputProcess connector
c86 cso30:c:InputProcess connector
c87 cso30:c:OutputProcess connector
p30_propro_p30
PMID: 16982211
This allows NF-kappaB to translocate to the nucleus (D4), where it induces the transcription of genes with an NF-kappaB consensus site in their promoter region, including IkappaBalpha.
c90 cso30:c:InputProcess connector
c91 cso30:c:OutputProcess connector
p32_propro_p32
PMID: 16982211
This newly synthesized IκBα can establish a negative-feedback loop by moving to the nucleus (D5), where it removes DNA-bound NF-kappaB complexes from their cognate sites and exports them back to the cytoplasm (D6).
c89 cso30:c:InputProcess connector
c102 cso30:c:InputProcess connector
c96 cso30:c:OutputProcess connector
p33_propro_p33
PMID: 16982211
This newly synthesized IκBα can establish a negative-feedback loop by moving to the nucleus (D5), where it removes DNA-bound NF-kappaB complexes from their cognate sites and exports them back to the cytoplasm (D6).
c93 cso30:c:InputAssociation connector
c92 cso30:c:OutputProcess connector
p34_propro_p34
PMID: 16982211
This newly synthesized IκBα can establish a negative-feedback loop by moving to the nucleus (D5), where it removes DNA-bound NF-kappaB complexes from their cognate sites and exports them back to the cytoplasm (D6).
c94 cso30:c:InputProcess connector
c95 cso30:c:OutputProcess connector
p35_propro_p35
PMID: 16982211
This newly synthesized IκBα can establish a negative-feedback loop by moving to the nucleus (D5), where it removes DNA-bound NF-kappaB complexes from their cognate sites and exports them back to the cytoplasm (D6).
c97 cso30:c:InputProcess connector
c98 cso30:c:OutputProcess connector
p36_propro_p36
PMID: 16982211
This newly synthesized IκBα can establish a negative-feedback loop by moving to the nucleus (D5), where it removes DNA-bound NF-kappaB complexes from their cognate sites and exports them back to the cytoplasm (D6).
c88 cso30:c:InputProcess connector
c101 cso30:c:InputAssociation connector
c99 cso30:c:OutputProcess connector
c100 cso30:c:OutputProcess connector
p37_propro_p37
PMID: 16982211
TLR-induced activation of NF-kappaB leads to the expression of several NF-kappaB-dependent genes, including cytokines such as tumor necrosis factor (TNF) and interleukin (IL)-1beta, both of which also directly activate the NF-kappaB pathway and thus establish a positive autoregulatory loop.
c103 cso30:c:InputAssociation connector
c104 cso30:c:OutputProcess connector
p40_propro_p40
PMID: 16982211
TLR-induced activation of NF-kappaB leads to the expression of several NF-kappaB-dependent genes, including cytokines such as tumor necrosis factor (TNF) and interleukin (IL)-1beta, both of which also directly activate the NF-kappaB pathway and thus establish a positive autoregulatory loop.
c107 cso30:c:InputProcess connector
c108 cso30:c:OutputProcess connector
p41_propro_p41
PMID: 16982211, 12360211
This simultaneous and well-orchestrated activation of NF-kappaB by PAMPs and pro-inflammatory cytokines leads to the production of NF-kappaB-dependent chemokines (e.g. IL-8 and eotaxin), adhesion molecules (e.g. E-selectin and intercellular adhesion molecule 1) and inducible enzymes (e.g. inducible nitric oxide synthase and cyclo-oxygenase-2), all of which contribute to the strength and duration of the inflammatory response.
c112 cso30:c:InputProcess connector
c113 cso30:c:OutputProcess connector
p42_propro_p42
PMID: 16982211, 12360211
This simultaneous and well-orchestrated activation of NF-kappaB by PAMPs and pro-inflammatory cytokines leads to the production of NF-kappaB-dependent chemokines (e.g. IL-8 and eotaxin), adhesion molecules (e.g. E-selectin and intercellular adhesion molecule 1) and inducible enzymes (e.g. inducible nitric oxide synthase and cyclo-oxygenase-2), all of which contribute to the strength and duration of the inflammatory response.
c111 cso30:c:InputAssociation connector
c114 cso30:c:OutputProcess connector
p43_propro_p43
PMID: 16982211, 12360211
This simultaneous and well-orchestrated activation of NF-kappaB by PAMPs and pro-inflammatory cytokines leads to the production of NF-kappaB-dependent chemokines (e.g. IL-8 and eotaxin), adhesion molecules (e.g. E-selectin and intercellular adhesion molecule 1) and inducible enzymes (e.g. inducible nitric oxide synthase and cyclo-oxygenase-2), all of which contribute to the strength and duration of the inflammatory response.
c115 cso30:c:InputAssociation connector
c116 cso30:c:OutputProcess connector
p44_propro_p44
PMID: 16982211, 12360211
This simultaneous and well-orchestrated activation of NF-kappaB by PAMPs and pro-inflammatory cytokines leads to the production of NF-kappaB-dependent chemokines (e.g. IL-8 and eotaxin), adhesion molecules (e.g. E-selectin and intercellular adhesion molecule 1) and inducible enzymes (e.g. inducible nitric oxide synthase and cyclo-oxygenase-2), all of which contribute to the strength and duration of the inflammatory response.
c117 cso30:c:InputProcess connector
c118 cso30:c:OutputProcess connector
p45_propro_p45
PMID: 16982211, 12360211
This simultaneous and well-orchestrated activation of NF-kappaB by PAMPs and pro-inflammatory cytokines leads to the production of NF-kappaB-dependent chemokines (e.g. IL-8 and eotaxin), adhesion molecules (e.g. E-selectin and intercellular adhesion molecule 1) and inducible enzymes (e.g. inducible nitric oxide synthase and cyclo-oxygenase-2), all of which contribute to the strength and duration of the inflammatory response.
c119 cso30:c:InputProcess connector
c120 cso30:c:OutputProcess connector
p46_propro_p46
PMID: 16982211, 12360211
This simultaneous and well-orchestrated activation of NF-kappaB by PAMPs and pro-inflammatory cytokines leads to the production of NF-kappaB-dependent chemokines (e.g. IL-8 and eotaxin), adhesion molecules (e.g. E-selectin and intercellular adhesion molecule 1) and inducible enzymes (e.g. inducible nitric oxide synthase and cyclo-oxygenase-2), all of which contribute to the strength and duration of the inflammatory response.
c122 cso30:c:InputAssociation connector
c121 cso30:c:OutputProcess connector
p47_propro_p47
PMID: 16982211, 12360211
This simultaneous and well-orchestrated activation of NF-kappaB by PAMPs and pro-inflammatory cytokines leads to the production of NF-kappaB-dependent chemokines (e.g. IL-8 and eotaxin), adhesion molecules (e.g. E-selectin and intercellular adhesion molecule 1) and inducible enzymes (e.g. inducible nitric oxide synthase and cyclo-oxygenase-2), all of which contribute to the strength and duration of the inflammatory response.
c126 cso30:c:InputAssociation connector
c125 cso30:c:OutputProcess connector
p48_propro_p48
PMID: 16982211, 12360211
This simultaneous and well-orchestrated activation of NF-kappaB by PAMPs and pro-inflammatory cytokines leads to the production of NF-kappaB-dependent chemokines (e.g. IL-8 and eotaxin), adhesion molecules (e.g. E-selectin and intercellular adhesion molecule 1) and inducible enzymes (e.g. inducible nitric oxide synthase and cyclo-oxygenase-2), all of which contribute to the strength and duration of the inflammatory response.
c123 cso30:c:InputProcess connector
c124 cso30:c:OutputProcess connector
p49_propro_p49
PMID: 16982211, 12360211
This simultaneous and well-orchestrated activation of NF-kappaB by PAMPs and pro-inflammatory cytokines leads to the production of NF-kappaB-dependent chemokines (e.g. IL-8 and eotaxin), adhesion molecules (e.g. E-selectin and intercellular adhesion molecule 1) and inducible enzymes (e.g. inducible nitric oxide synthase and cyclo-oxygenase-2), all of which contribute to the strength and duration of the inflammatory response.
c127 cso30:c:InputProcess connector
c128 cso30:c:OutputProcess connector
p50_propro_p50
PMID: 16982211, 12360211
This simultaneous and well-orchestrated activation of NF-kappaB by PAMPs and pro-inflammatory cytokines leads to the production of NF-kappaB-dependent chemokines (e.g. IL-8 and eotaxin), adhesion molecules (e.g. E-selectin and intercellular adhesion molecule 1) and inducible enzymes (e.g. inducible nitric oxide synthase and cyclo-oxygenase-2), all of which contribute to the strength and duration of the inflammatory response.
c130 cso30:c:InputAssociation connector
c129 cso30:c:OutputProcess connector
p51_propro_p51
PMID: 16982211, 12360211
This simultaneous and well-orchestrated activation of NF-kappaB by PAMPs and pro-inflammatory cytokines leads to the production of NF-kappaB-dependent chemokines (e.g. IL-8 and eotaxin), adhesion molecules (e.g. E-selectin and intercellular adhesion molecule 1) and inducible enzymes (e.g. inducible nitric oxide synthase and cyclo-oxygenase-2), all of which contribute to the strength and duration of the inflammatory response.
c131 cso30:c:InputProcess connector
c132 cso30:c:OutputProcess connector
p52_propro_p52
PMID: 16982211, 12360211
This simultaneous and well-orchestrated activation of NF-kappaB by PAMPs and pro-inflammatory cytokines leads to the production of NF-kappaB-dependent chemokines (e.g. IL-8 and eotaxin), adhesion molecules (e.g. E-selectin and intercellular adhesion molecule 1) and inducible enzymes (e.g. inducible nitric oxide synthase and cyclo-oxygenase-2), all of which contribute to the strength and duration of the inflammatory response.
c134 cso30:c:InputAssociation connector
c133 cso30:c:OutputProcess connector
p53_propro_p53
PMID: 16982211, 8557994, 8692885
Because overexpression of A20 was shown to inhibit NF-kappaB activation in response to many stimuli including TNF and IL-1 19 and 20, it was originally suggested that A20 is a feedback inhibitor of NF-kappaB signalling.
PMID: 16982211, 8557994, 11463333, 16204640
Interestingly, overexpression of these genes was shown to inhibit TNF-induced and IL-1-induced NF-kappaB activation.
c141 cso30:c:InputAssociation connector
c139 cso30:c:OutputProcess connector
p54_propro_p54
PMID: 16982211, 8557994, 8692885
Because overexpression of A20 was shown to inhibit NF-kappaB activation in response to many stimuli including TNF and IL-1 19 and 20, it was originally suggested that A20 is a feedback inhibitor of NF-kappaB signalling.
PMID: 16982211, 8557994, 11463333, 16204640
Interestingly, overexpression of these genes was shown to inhibit TNF-induced and IL-1-induced NF-kappaB activation.
c142 cso30:c:InputAssociation connector
c140 cso30:c:OutputProcess connector
p55_propro_p55
PMID: 16982211, 15334086, 15258597, 15653317
It was subsequently demonstrated that A20 can disassemble K63 polyubiquitin chains from RIP and TRAF6 in the TNF-receptor-induced and TLR4 [lipopolysaccharide (LPS)]-induced NF-kappaB signalling pathway, respectively.
c138 cso30:c:InputProcess connector
c144 cso30:c:InputAssociation connector
c145 cso30:c:OutputProcess connector
p56_propro_p56
PMID: 16982211, 15334086, 15258597, 15653317
It was subsequently demonstrated that A20 can disassemble K63 polyubiquitin chains from RIP and TRAF6 in the TNF-receptor-induced and TLR4 [lipopolysaccharide (LPS)]-induced NF-kappaB signalling pathway, respectively.
PMID: 16982211, 15258597, 15653317
The de-ubiquitinating and Ub-conjugating activities of A20 are ordered in two steps: the N-terminal OTU domain of A20 first removes the K63-linked polyubiquitin chains from RIP and inactivates it, and the C-terminal zinc finger domain of A20 catalyses K48 polyubiquitination of RIP, thereby targeting it for proteasomal degradation.
c137 cso30:c:InputProcess connector
c143 cso30:c:InputAssociation connector
c146 cso30:c:OutputProcess connector
p57_propro_p57
PMID: 16982211, 16684768
Recently, TNF-induced IKKgamma ubiquitination was also reported to be sensitive to A20-mediated de-ubiquitination, indicating that A20 might act at different levels of the NF-kappaB signalling pathway.
c147 cso30:c:InputProcess connector
c148 cso30:c:OutputProcess connector
p58_propro_p58
PMID: 16982211, 16684768
Recently, TNF-induced IKKgamma ubiquitination was also reported to be sensitive to A20-mediated de-ubiquitination, indicating that A20 might act at different levels of the NF-kappaB signalling pathway.
c149 cso30:c:InputProcess connector
c151 cso30:c:InputAssociation connector
c150 cso30:c:OutputProcess connector
p59_propro_p59
PMID: 16982211, 11463333, 12682062
One of them is OTUD7B (also known as Cezanne), which interacts with TRAF6 and inhibits NF-kappaB activation upon overexpression.
c152 cso30:c:InputProcess connector
c153 cso30:c:InputProcess connector
c154 cso30:c:OutputProcess connector
p60_propro_p60
PMID: 16982211, 12917690, 12917691, 12917689
Overexpression of CYLD interferes with IKK activation by catalysing the selective cleavage of K63 polyubiquitin chains from TRAF2 and TRAF6, consistent with its inhibitory effect on both TNF-receptor- and TLRIL-1-receptor-initiated NF-kappaB activation.
PMID: 16982211, 11907583, 12411493
For example, the TNF-induced recruitment of TRAF2 to TNF receptor-1 (the main receptor for soluble TNF on most cell types) and TNF receptor-2 (the main receptor for membrane-bound TNF, and primarily expressed on T cells) is followed by TRAF2 ubiquitination by two RING finger Ub ligases: baculoviral IAP repeat-containing 2 (BIRC2; also known as cIAP1) and seven in absentia homolog 2 (SIAH2).
c155 cso30:c:InputProcess connector
c157 cso30:c:InputAssociation connector
c216 cso30:c:InputAssociation connector
c217 cso30:c:InputAssociation connector
c156 cso30:c:OutputProcess connector
p61_propro_p61
PMID: 16982211, 12917690, 12917691, 12917689
Overexpression of CYLD interferes with IKK activation by catalysing the selective cleavage of K63 polyubiquitin chains from TRAF2 and TRAF6, consistent with its inhibitory effect on both TNF-receptor- and TLRIL-1-receptor-initiated NF-kappaB activation.
PMID: 16982211, 16543409
Instead, SOCS3 decreased TRAF6 polyubiquitination, thus preventing the association and activation of TAK1.
c135 cso30:c:InputProcess connector
c158 cso30:c:InputAssociation connector
c136 cso30:c:OutputProcess connector
p62_propro_p62
PMID: 16982211, 16230348, 15226292
Moreover, endogenous expression of CYLD is upregulated by TNF, IL-1 and TLR2 ligands in an NF-kappaB-dependent way, supporting a negative-feedback role for CYLD in the NF-kappaB pathway.
c160 cso30:c:InputProcess connector
c159 cso30:c:OutputProcess connector
p63_propro_p63
PMID: 16982211, 16713561
For example, CYLD was recently shown to de-ubiquitinate B-cell CLL/lymphoma 3 (BCL3), preventing its nuclear translocation.
c161 cso30:c:InputProcess connector
c162 cso30:c:OutputProcess connector
p64_propro_p64
PMID: 16982211, 16713561
For example, CYLD was recently shown to de-ubiquitinate B-cell CLL/lymphoma 3 (BCL3), preventing its nuclear translocation.
c163 cso30:c:InputProcess connector
c167 cso30:c:InputAssociation connector
c164 cso30:c:OutputProcess connector
p65_propro_p65
PMID: 16982211, 16713561
For example, CYLD was recently shown to de-ubiquitinate B-cell CLL/lymphoma 3 (BCL3), preventing its nuclear translocation.
c165 cso30:c:InputProcess connector
c199 cso30:c:InputInhibitor connector
c166 cso30:c:OutputProcess connector
p66_propro_p66
PMID: 16982211, 16214042
Recently, ubiquitin specific peptidase 31 (USP31) was identified as another TRAF2 binding DUB that inhibits TNF-induced NF-kappaB activation upon overexpression.
c168 cso30:c:InputProcess connector
c169 cso30:c:InputProcess connector
c170 cso30:c:OutputProcess connector
p67_propro_p67
PMID: 16982211, 15107846
In this context, the RING finger containing Ub ligase Triad3A was shown to bind and induce the ubiquitination and degradation of TLR4 and TLR9, but not TLR2.
c172 cso30:c:InputProcess connector
c173 cso30:c:InputProcess connector
c174 cso30:c:OutputProcess connector
p68_propro_p68
PMID: 16982211, 15107846
In this context, the RING finger containing Ub ligase Triad3A was shown to bind and induce the ubiquitination and degradation of TLR4 and TLR9, but not TLR2.
c175 cso30:c:InputProcess connector
c176 cso30:c:InputProcess connector
c177 cso30:c:OutputProcess connector
p69_propro_p69
PMID: 16982211, 15107846
In this context, the RING finger containing Ub ligase Triad3A was shown to bind and induce the ubiquitination and degradation of TLR4 and TLR9, but not TLR2.
c178 cso30:c:InputProcess connector
c179 cso30:c:OutputProcess connector
p70_propro_p70
PMID: 16982211, 15107846
In this context, the RING finger containing Ub ligase Triad3A was shown to bind and induce the ubiquitination and degradation of TLR4 and TLR9, but not TLR2.
c180 cso30:c:InputProcess connector
c181 cso30:c:OutputProcess connector
p71_propro_p71
PMID: 16982211, 15107846
In this context, the RING finger containing Ub ligase Triad3A was shown to bind and induce the ubiquitination and degradation of TLR4 and TLR9, but not TLR2.
c182 cso30:c:InputProcess connector
c185 cso30:c:OutputProcess connector
p72_propro_p72
PMID: 16982211, 15107846
In this context, the RING finger containing Ub ligase Triad3A was shown to bind and induce the ubiquitination and degradation of TLR4 and TLR9, but not TLR2.
c183 cso30:c:InputProcess connector
c184 cso30:c:OutputProcess connector
p73_propro_p73
PMID: 16982211, 15899873
In addition, TNF-receptor-2 plasma-membrane levels are regulated by TNF-induced K48 polyubiquitination mediated by Ankyrin repeat and SOCS box-containing 3 (ASB3), which confers its Ub-ligase activity via an interaction with elongin Belongin C and the recruitment of the Ub-transferase system composed of cullin-2, Rbx2 and E2.
PMID: 16982211
SOCS proteins are characterized by a C-terminal SOCS-box domain that allows the binding of the elongin-Belongin-C complex to form a functional E3 Ub ligase.
c186 cso30:c:InputProcess connector
c188 cso30:c:InputProcess connector
c189 cso30:c:InputProcess connector
c190 cso30:c:InputProcess connector
c191 cso30:c:InputProcess connector
c195 cso30:c:InputProcess connector
c187 cso30:c:OutputProcess connector
p76_propro_p76
PMID: 16982211, 15899873
In addition, TNF-receptor-2 plasma-membrane levels are regulated by TNF-induced K48 polyubiquitination mediated by Ankyrin repeat and SOCS box-containing 3 (ASB3), which confers its Ub-ligase activity via an interaction with elongin Belongin C and the recruitment of the Ub-transferase system composed of cullin-2, Rbx2 and E2.
c192 cso30:c:InputProcess connector
c194 cso30:c:InputAssociation connector
c193 cso30:c:OutputProcess connector
p74_propro_p74
PMID: 16982211, 11907583, 12411493
For example, the TNF-induced recruitment of TRAF2 to TNF receptor-1 (the main receptor for soluble TNF on most cell types) and TNF receptor-2 (the main receptor for membrane-bound TNF, and primarily expressed on T cells) is followed by TRAF2 ubiquitination by two RING finger Ub ligases: baculoviral IAP repeat-containing 2 (BIRC2; also known as cIAP1) and seven in absentia homolog 2 (SIAH2).
c196 cso30:c:InputProcess connector
c197 cso30:c:InputProcess connector
c105 cso30:c:OutputProcess connector
p75_propro_p75
PMID: 16982211, 11907583, 12411493
For example, the TNF-induced recruitment of TRAF2 to TNF receptor-1 (the main receptor for soluble TNF on most cell types) and TNF receptor-2 (the main receptor for membrane-bound TNF, and primarily expressed on T cells) is followed by TRAF2 ubiquitination by two RING finger Ub ligases: baculoviral IAP repeat-containing 2 (BIRC2; also known as cIAP1) and seven in absentia homolog 2 (SIAH2).
c198 cso30:c:InputProcess connector
c51 cso30:c:InputProcess connector
c200 cso30:c:OutputProcess connector
p77_propro_p77
PMID: 16982211, 11907583, 12411493
For example, the TNF-induced recruitment of TRAF2 to TNF receptor-1 (the main receptor for soluble TNF on most cell types) and TNF receptor-2 (the main receptor for membrane-bound TNF, and primarily expressed on T cells) is followed by TRAF2 ubiquitination by two RING finger Ub ligases: baculoviral IAP repeat-containing 2 (BIRC2; also known as cIAP1) and seven in absentia homolog 2 (SIAH2).
c201 cso30:c:InputProcess connector
c202 cso30:c:InputProcess connector
c203 cso30:c:OutputProcess connector
p78_propro_p78
PMID: 16982211, 11907583, 15861135
Binding of BIRC2 to TRAF2 at TNF receptor-2 induces the translocation of the TRAF2BIRC2 complex to an endoplasmic-reticulum-associated compartment, where BIRC2 ubiquitinates TRAF2, thereby triggering its proteasomal degradation and the subsequent cessation of TRAF2-mediated signalling.
PMID: 16982211, 11907583, 12411493
For example, the TNF-induced recruitment of TRAF2 to TNF receptor-1 (the main receptor for soluble TNF on most cell types) and TNF receptor-2 (the main receptor for membrane-bound TNF, and primarily expressed on T cells) is followed by TRAF2 ubiquitination by two RING finger Ub ligases: baculoviral IAP repeat-containing 2 (BIRC2; also known as cIAP1) and seven in absentia homolog 2 (SIAH2).
c208 cso30:c:InputProcess connector
c209 cso30:c:InputAssociation connector
c212 cso30:c:InputProcess connector
c205 cso30:c:OutputProcess connector
p79_propro_p79
PMID: 16982211, 11907583, 15861135
Binding of BIRC2 to TRAF2 at TNF receptor-2 induces the translocation of the TRAF2BIRC2 complex to an endoplasmic-reticulum-associated compartment, where BIRC2 ubiquitinates TRAF2, thereby triggering its proteasomal degradation and the subsequent cessation of TRAF2-mediated signalling.
c204 cso30:c:InputProcess connector
c206 cso30:c:InputProcess connector
c207 cso30:c:OutputProcess connector
p80_propro_p80
PMID: 16982211, 11907583, 15861135
Binding of BIRC2 to TRAF2 at TNF receptor-2 induces the translocation of the TRAF2BIRC2 complex to an endoplasmic-reticulum-associated compartment, where BIRC2 ubiquitinates TRAF2, thereby triggering its proteasomal degradation and the subsequent cessation of TRAF2-mediated signalling.
c210 cso30:c:InputProcess connector
c211 cso30:c:OutputProcess connector
p81_propro_p81
PMID: 16982211, 11907583, 15861135
Binding of BIRC2 to TRAF2 at TNF receptor-2 induces the translocation of the TRAF2BIRC2 complex to an endoplasmic-reticulum-associated compartment, where BIRC2 ubiquitinates TRAF2, thereby triggering its proteasomal degradation and the subsequent cessation of TRAF2-mediated signalling.
PMID: 16982211, 12411493
Similarly, the triggering of TNF receptor-1 induces proteasomal degradation of TRAF2 upon overexpression of the E3 Ub ligase SIAH2.
c213 cso30:c:InputProcess connector
c218 cso30:c:InputAssociation connector
c214 cso30:c:OutputProcess connector
c215 cso30:c:OutputProcess connector
p82_propro_p82
PMID: 16982211, 15258597, 15653317
The de-ubiquitinating and Ub-conjugating activities of A20 are ordered in two steps: the N-terminal OTU domain of A20 first removes the K63-linked polyubiquitin chains from RIP and inactivates it, and the C-terminal zinc finger domain of A20 catalyses K48 polyubiquitination of RIP, thereby targeting it for proteasomal degradation.
c219 cso30:c:InputProcess connector
c220 cso30:c:OutputProcess connector
p83_propro_p83
PMID: 16982211, 8557994, 11463333, 16204640
Interestingly, overexpression of these genes was shown to inhibit TNF-induced and IL-1-induced NF-kappaB activation.
c226 cso30:c:OutputProcess connector
p84_propro_p84
PMID: 16982211, 8557994, 11463333, 16204640
Interestingly, overexpression of these genes was shown to inhibit TNF-induced and IL-1-induced NF-kappaB activation.
c228 cso30:c:OutputProcess connector
p85_propro_p85
PMID: 16982211, 8557994, 11463333, 16204640
Interestingly, overexpression of these genes was shown to inhibit TNF-induced and IL-1-induced NF-kappaB activation.
c229 cso30:c:OutputProcess connector
p86_propro_p86
PMID: 16982211, 8557994, 11463333, 16204640
Interestingly, overexpression of these genes was shown to inhibit TNF-induced and IL-1-induced NF-kappaB activation.
c227 cso30:c:OutputProcess connector
p87_propro_p87
PMID: 16982211, 16415872
Recently, it was observed that the TLR2 and TLR4 adaptor protein MyD88 adaptor-like (MAL, also known as TIRAP) is phosphorylated and ubiquitinated in a SOCS1-dependent manner upon TLR stimulation, thereby targeting MAL for proteasomal degradation.
c230 cso30:c:InputAssociation connector
c231 cso30:c:InputProcess connector
c232 cso30:c:OutputProcess connector
p88_propro_p88
PMID: 16982211, 16415872
Recently, it was observed that the TLR2 and TLR4 adaptor protein MyD88 adaptor-like (MAL, also known as TIRAP) is phosphorylated and ubiquitinated in a SOCS1-dependent manner upon TLR stimulation, thereby targeting MAL for proteasomal degradation.
c233 cso30:c:InputProcess connector
c234 cso30:c:OutputProcess connector
p89_propro_p89
PMID: 16982211, 16415872
Recently, it was observed that the TLR2 and TLR4 adaptor protein MyD88 adaptor-like (MAL, also known as TIRAP) is phosphorylated and ubiquitinated in a SOCS1-dependent manner upon TLR stimulation, thereby targeting MAL for proteasomal degradation.
c235 cso30:c:InputProcess connector
c238 cso30:c:InputAssociation connector
c236 cso30:c:OutputProcess connector
c237 cso30:c:OutputProcess connector
p90_propro_p90
PMID: 16982211, 12433373, 14690596
Indeed, an interaction of SOCS1 with IRAK1 as well as SOCS1-mediated ubiquitination and subsequent degradation of the p65 NF-κB subunit suggest a more downstream inhibitory effect of SOCS1 in TLR signalling pathways.
c239 cso30:c:InputProcess connector
c243 cso30:c:InputAssociation connector
c240 cso30:c:OutputProcess connector
p91_propro_p91
PMID: 16982211, 12433373, 14690596
Indeed, an interaction of SOCS1 with IRAK1 as well as SOCS1-mediated ubiquitination and subsequent degradation of the p65 NF-κB subunit suggest a more downstream inhibitory effect of SOCS1 in TLR signalling pathways.
c241 cso30:c:InputProcess connector
c244 cso30:c:InputAssociation connector
c242 cso30:c:OutputProcess connector
p92_propro_p92
PMID: 16982211, 12433373, 14690596
Indeed, an interaction of SOCS1 with IRAK1 as well as SOCS1-mediated ubiquitination and subsequent degradation of the p65 NF-κB subunit suggest a more downstream inhibitory effect of SOCS1 in TLR signalling pathways.
c245 cso30:c:InputProcess connector
c246 cso30:c:InputProcess connector
c247 cso30:c:OutputProcess connector
p93_propro_p93
PMID: 16982211, 16543409
This is further supported by the finding that overexpression of SOCS3 inhibits IL-1-induced NF-kappaB activation and co-immunoprecipitates with the TRAF6TAK1 complex.
c248 cso30:c:InputProcess connector
c249 cso30:c:InputProcess connector
c250 cso30:c:InputProcess connector
c251 cso30:c:OutputProcess connector
p94_propro_p94
PMID: 16982211, 16543409
This is further supported by the finding that overexpression of SOCS3 inhibits IL-1-induced NF-kappaB activation and co-immunoprecipitates with the TRAF6TAK1 complex.
PMID: 16982211, 16543409
Instead, SOCS3 decreased TRAF6 polyubiquitination, thus preventing the association and activation of TAK1.
c253 cso30:c:InputProcess connector
c256 cso30:c:InputInhibitor connector
c254 cso30:c:OutputProcess connector
LPS_enti_MO000042409
LPS
TRAF6_enti_MO000000212
TRAF6
TAK1_enti_MO000016574
TAK1
TAB2_enti_MO000022125
TAB2
TAB3_enti_MO000041541
TAB3
TNFR_enti_MO000000205
TNFR
RIP_enti_MO000000208
RIP
TNF-alpha_enti_e5
TNF-alpha
TNF-alpha: TNFR_enti_e6
TNF-alpha: TNFR
TNF-alpha: TNFR: TRADD_enti_e11
TNF-alpha: TNFR: TRADD
TRADD_enti_MO000000207
TRADD
TRAF2_enti_MO000000209
TRAF2
TNF-alpha: TNFR: TRADD: TRAF2: RIP_enti_e12
TNF-alpha: TNFR: TRADD: TRAF2: RIP
TNF-alpha: TNFR: TRADD: TRAF2 {ubK63}n: RIP_enti_e13
TNF-alpha: TNFR: TRADD: TRAF2 {ubK63}n: RIP
TRAF2 {ubK63}n: RIP_enti_e15
TRAF2 {ubK63}n: RIP
TRAF2 {ub}n: RIP {ubK63}n_enti_e14
TRAF2 {ub}n: RIP {ubK63}n
TRAF2 {ub}n: RIP {ubK63}n: TAB2: TAB3: IKK-alpha:IKK-beta:(IKK-gamma)2_enti_e16
TRAF2 {ub}n: RIP {ubK63}n: TAB2: TAB3: IKK-alpha:IKK-beta:(IKK-gamma)2
IKK-alpha:IKK-beta:(IKK-gamma)2_enti_MO000016661
IKK-alpha:IKK-beta:(IKK-gamma)2
TRAF2 {ub}n: RIP {ubK63}n: TAB2: TAB3: IKK-alpha {p}:IKK-beta {p}:(IKK-gamma)2 : TAK1_enti_e17
TRAF2 {ub}n: RIP {ubK63}n: TAB2: TAB3: IKK-alpha {p}:IKK-beta {p}:(IKK-gamma)2 : TAK1
TRAF2 {ub}n: RIP {ubK63}n: TAB2: TAB3: IKK-alpha:IKK-beta:(IKK-gamma)2: TAK1_enti_e19
TRAF2 {ub}n: RIP {ubK63}n: TAB2: TAB3: IKK-alpha:IKK-beta:(IKK-gamma)2: TAK1
IL-1beta_enti_MO000016597
IL-1beta
IL-1beta:IL-1RI:IL-1RAcP:MyD88_enti_MO000039096
IL-1beta:IL-1RI:IL-1RAcP:MyD88
IL-1RI: IL-RAcP_enti_e18
IL-1RI: IL-RAcP
IL-1beta: IL-1RI: IL-RAcP_enti_e20
IL-1beta: IL-1RI: IL-RAcP
MyD88_enti_MO000016573
MyD88
TLR4: MD-2: CD14_enti_e21
TLR4: MD-2: CD14
LPS: TLR4: MD-2: CD14_enti_e22
LPS: TLR4: MD-2: CD14
LPS: TLR4: MD-2: CD14: MyD88_enti_e23
LPS: TLR4: MD-2: CD14: MyD88
LPS: TLR4: MD-2: CD14: MAL_enti_e24
LPS: TLR4: MD-2: CD14: MAL
MAL_enti_MO000068831
MAL
IRAK-1_enti_MO000000213
IRAK-1
IRAK-4_enti_MO000039077
IRAK-4
LPS: TLR4: MD-2: CD14: MyD88: IRAK-1: IRAK-4_enti_e25
LPS: TLR4: MD-2: CD14: MyD88: IRAK-1: IRAK-4
LPS: TLR4: MD-2: CD14: MyD88: IRAK-1: IRAK-4: TRAF6_enti_e26
LPS: TLR4: MD-2: CD14: MyD88: IRAK-1: IRAK-4: TRAF6
IL-1beta:IL-1RI:IL-1RAcP:MyD88: IRAK-1: IRAK-4_enti_e27
IL-1beta:IL-1RI:IL-1RAcP:MyD88: IRAK-1: IRAK-4
IL-1beta:IL-1RI:IL-1RAcP:MyD88: IRAK-1: IRAK-4: TRAF6_enti_e28
IL-1beta:IL-1RI:IL-1RAcP:MyD88: IRAK-1: IRAK-4: TRAF6
IL-1beta:IL-1RI:IL-1RAcP:MyD88: IRAK-1{p}: IRAK-4: TRAF6_enti_e29
IL-1beta:IL-1RI:IL-1RAcP:MyD88: IRAK-1{p}: IRAK-4: TRAF6
LPS: TLR4: MD-2: CD14: MyD88: IRAK-1{p}: IRAK-4: TRAF6_enti_e30
LPS: TLR4: MD-2: CD14: MyD88: IRAK-1{p}: IRAK-4: TRAF6
IL-1beta:IL-1RI:IL-1RAcP:MyD88: IRAK-4_enti_e31
IL-1beta:IL-1RI:IL-1RAcP:MyD88: IRAK-4
LPS: TLR4: MD-2: CD14: MyD88: IRAK-4_enti_e32
LPS: TLR4: MD-2: CD14: MyD88: IRAK-4
IRAK-1 {p}: TRAF6_enti_e34
IRAK-1 {p}: TRAF6
IRAK-1 {p}: TRAF6 {ubK63}n_enti_e33
IRAK-1 {p}: TRAF6 {ubK63}n
TAK1: TAB2: TAB3_enti_e35
TAK1: TAB2: TAB3
IRAK-1 {p}: TRAF6 {ubK63}n: TAK1: TAb2: TAb3_enti_e36
IRAK-1 {p}: TRAF6 {ubK63}n: TAK1: TAb2: TAb3
IKK-alpha {p}:IKK-beta {p}:(IKK-gamma)2_enti_e37
IKK-alpha {p}:IKK-beta {p}:(IKK-gamma)2
p50:RelA-p65:IkappaB-alpha{p}_enti_MO000000254
p50:RelA-p65:IkappaB-alpha{p}
p50:RelA-p65:IkappaB-alpha_enti_MO000038724
p50:RelA-p65:IkappaB-alpha
p50:RelA-p65:IkappaB-alpha{p} {ubK48}_enti_e38
p50:RelA-p65:IkappaB-alpha{p} {ubK48}
protein remnants_enti_MO000019479
protein remnants
IkappaB-alpha_enti_MO000000233
IkappaB-alpha
IkappaBalpha_enti_G010819
IkappaBalpha
p50:RelA-p65 {activated}_enti_MO000016632
p50:RelA-p65 {activated}
p50:RelA-p65 {nucleus}_enti_e39
p50:RelA-p65 {nucleus}
NF-kappaB responsive genes: p50:RelA-p65_enti_e40
NF-kappaB responsive genes: p50:RelA-p65
NF-kappaB responsive genes_enti_e41
NF-kappaB responsive genes
IkappaB-alpha (cytoplasmic)_enti_e42
IkappaB-alpha (cytoplasmic)
p50:RelA-p65:IkappaB-alpha {nucleus}_enti_e43
p50:RelA-p65:IkappaB-alpha {nucleus}
TNF-alpha_enti_G010329
TNF-alpha
IL-1beta_enti_G010389
IL-1beta
IL-8_enti_MO000017264
IL-8
IL-8_enti_e44
IL-8
Eotaxin_enti_e45
Eotaxin
Eotaxin_enti_e46
Eotaxin
SELE_enti_G010334
SELE
SELE_enti_MO000067812
SELE
ICAM-1_enti_G010431
ICAM-1
ICAM-1_enti_MO000000306
ICAM-1
iNOS_enti_G010514
iNOS
iNOS_enti_MO000021201
iNOS
COX2_enti_G029941
COX2
COX-2_enti_MO000017266
COX-2
CYLD_enti_MO000041169
CYLD
A20_enti_MO000016591
A20
A20_enti_G010405
A20
IL-1_enti_MO000000214
IL-1
TRAF2 {ub}n: RIP {ubK63}n: TAB2: TAB3: IKK-alpha {p}:IKK-beta {p}:(IKK-gamma)2 {ub}: TAK1_enti_e47
TRAF2 {ub}n: RIP {ubK63}n: TAB2: TAB3: IKK-alpha {p}:IKK-beta {p}:(IKK-gamma)2 {ub}: TAK1
OTUD7B_enti_e48
OTUD7B
TRAF6: OTUD7B_enti_e49
TRAF6: OTUD7B
CYLD_enti_G013179
CYLD
Bcl-3_enti_MO000000238
Bcl-3
Bcl-3 {ub}_enti_e63
Bcl-3 {ub}
Bcl-3 {ub}{nucleus}_enti_e64
Bcl-3 {ub}{nucleus}
USP31_enti_MO000090775
USP31
TRAF2: USP31_enti_e65
TRAF2: USP31
TLR4_enti_MO000019394
TLR4
TLR9_enti_MO000042012
TLR9
TLR4: TRIAD3A_enti_e66
TLR4: TRIAD3A
TLR9: TRIAD3A_enti_e67
TLR9: TRIAD3A
TRIAD3A_enti_e68
TRIAD3A
TLR9 {ub}n: TRIAD3A_enti_e69
TLR9 {ub}n: TRIAD3A
TLR4 {ub}n: TRIAD3A_enti_e70
TLR4 {ub}n: TRIAD3A
TNFR2_enti_MO000016921
TNFR2
elongin C_enti_MO000018946
elongin C
elongin B_enti_MO000018947
elongin B
Cullin-2_enti_MO000018939
Cullin-2
ASB3_enti_e71
ASB3
Rbx2_enti_e72
Rbx2
ASB3: elongin B: elongin C: cullin-2: Rbx2: E2_enti_e74
ASB3: elongin B: elongin C: cullin-2: Rbx2: E2
E2_enti_MO000099670
E2
TNFR2 {ubK48}n_enti_e73
TNFR2 {ubK48}n
TNF: TNFR2_enti_e75
TNF: TNFR2
TNF: TNFR2: TRAF2_enti_e76
TNF: TNFR2: TRAF2
BIRC2_enti_e77
BIRC2
TNF-alpha: TNFR2: TRAF2 {ub}: BIRC2_enti_e78
TNF-alpha: TNFR2: TRAF2 {ub}: BIRC2
TNF: TNFR2: TRAF2: BIRC2_enti_e79
TNF: TNFR2: TRAF2: BIRC2
Siah-2_enti_MO000021586
Siah-2
TNF-alpha: TNFR2: TRAF2: BIRC2_enti_e86
TNF-alpha: TNFR2: TRAF2: BIRC2
e87_enti_e87
e87
RABGEF1_enti_e88
RABGEF1
Zfand6_enti_e89
Zfand6
OTUD7B_enti_e90
OTUD7B
Zfand5_enti_e91
Zfand5
SOCS-1_enti_MO000017004
SOCS-1
LPS: TLR4: MD-2: CD14: MAL {ub}_enti_e92
LPS: TLR4: MD-2: CD14: MAL {ub}
LPS: TLR4: MD-2: CD14: MAL {p}_enti_e93
LPS: TLR4: MD-2: CD14: MAL {p}
p50: RelA-p65 {ub}n_enti_e94
p50: RelA-p65 {ub}n
IRAK1: SOCS-1_enti_e95
IRAK1: SOCS-1
SOCS-3_enti_MO000017121
SOCS-3
TRAF6: TAK1: SOCS-1_enti_e96
TRAF6: TAK1: SOCS-1
IRAK-1 {p}: TRAF6 {ubK63}n: TAK1 {activated}: TAb2: TAb3_enti_e97
IRAK-1 {p}: TRAF6 {ubK63}n: TAK1 {activated}: TAb2: TAb3
TNF_enti_MO000000204
TNF
TNF-alpha: TNFR2_enti_e106
TNF-alpha: TNFR2