_enti_e7
_enti_e8
_enti_e9
_enti_e1
_enti_e3
_enti_e2
_enti_e4
_enti_e55
_enti_e53
_enti_e59
_enti_e51
_enti_e52
_enti_e54
_enti_e50
_enti_e57
_enti_e58
_enti_e61
_enti_e60
_enti_e62
g1_fact_g1
g2_fact_g12
g2_fact_g13
g1_fact_g14
p1_propro_p1
PMID: 17706453
Furthermore, MDA5 and RIG-I recognize different types of dsRNAs: MDA5 recognizes poly(I:C), and RIG-I detects in vitro transcribed dsRNAs.
c1 cso30:c:InputProcess connector
c2 cso30:c:InputProcess connector
c3 cso30:c:OutputProcess connector
p1_propro_p2
PMID: 17706453
Furthermore, MDA5 and RIG-I recognize different types of dsRNAs: MDA5 recognizes poly(I:C), and RIG-I detects in vitro transcribed dsRNAs.
c4 cso30:c:InputProcess connector
c5 cso30:c:InputProcess connector
c6 cso30:c:OutputProcess connector
p3_propro_p3
PMID:17706453
TRIM25 alpha contains a RING-finger domain, a B box/coiled-coil domain and a SPRY domain and induces robust ubiquitination of the CARD domains of RIG-I.
PMID: 17706453
The carboxy-terminal SPRY domain of TRIM25 alpha interacts with the N-terminal CARDs of RIG-I; this interaction effectively delivers the Lys 63-linked ubiquitin moiety to the N-terminal CARDs of RIG-I, resulting in a marked increase in RIG-I downstream signaling activity.
c7 cso30:c:InputProcess connector
c8 cso30:c:InputProcess connector
c9 cso30:c:OutputProcess connector
p4_propro_p4
PMID: 17706453
The carboxy-terminal SPRY domain of TRIM25 alpha interacts with the N-terminal CARDs of RIG-I; this interaction effectively delivers the Lys 63-linked ubiquitin moiety to the N-terminal CARDs of RIG-I, resulting in a marked increase in RIG-I downstream signaling activity.
c10 cso30:c:InputProcess connector
c11 cso30:c:OutputProcess connector
p5_propro_p5
PMID: 17706453,16785313,16125763,16153868,16177806
The adaptor molecule providing a link between RIG-I sensing of incoming viral RNA and downstream activation events was independently elucidated as mitochondrial antiviral signaling adapter (MAVS), also known as (IPS-1/VISA/Cardif)
PMID: 17706453,16177806
MAVS interacts with RIG-I and recruits IKKvar epsilon through its C-terminal region; knockdown by siRNA inhibited RIG-I-dependent antiviral responses
c12 cso30:c:InputProcess connector
c13 cso30:c:InputProcess connector
c14 cso30:c:OutputProcess connector
p6_propro_p6
PMID: 17706453
TRAF3 and/or TRAF6 are also recruited to MAVS through a direct interaction with a TRAF-interaction motif within MAVS.
c15 cso30:c:InputProcess connector
c16 cso30:c:InputProcess connector
c17 cso30:c:OutputProcess connector
p7_propro_p7
PMID: 17706453,17047224
Inducible activation of canonical NF-κB signaling requires phosphorylation of the IκB inhibitor by the 700900 kDa multi-protein canonical IKK complex composed of two catalytic kinase subunits, IKKgreek small letter alpha and IKKβ, and a non-enzymatic regulatory subunit NF-κB Essential Modulator (NEMO) or IKKγ
c18 cso30:c:InputProcess connector
c19 cso30:c:InputProcess connector
c20 cso30:c:InputProcess connector
c21 cso30:c:OutputProcess connector
p8_propro_p8
PMID: 17706453,10759890
Both TBK-1 and IKK epsilon interact with the TNF-receptor-associated factor (TRAF)-interacting protein/TRAF family member-associated NF-κB activator (I-TRAF/TANK) protein, a modulator of TNF alpha-induced NF-κB activation
c22 cso30:c:InputProcess connector
c23 cso30:c:InputProcess connector
c32 cso30:c:InputProcess connector
c25 cso30:c:OutputProcess connector
p9_propro_p9
PMID: 17706543,14560022
Associated Protein 1 (NAP1), a homologue of I-TRAF/TANK, has also been shown to directly interact with TBK-1 and IKK epsilon
c26 cso30:c:InputProcess connector
c27 cso30:c:InputProcess connector
c28 cso30:c:InputProcess connector
c29 cso30:c:OutputProcess connector
p11_propro_p11
PMID: 17706543,10759890
Overexpression of IKKvar epsilon or TBK-1 induces phosphorylation of I-TRAF/TANK, which results in its dissociation from TRAF2 and subsequent activation of NF-κB transcription through the classical IKK pathway
c33 cso30:c:InputProcess connector
c34 cso30:c:OutputProcess connector
p12_propro_p12
PMID: 17706543,10759890
Overexpression of IKKvar epsilon or TBK-1 induces phosphorylation of I-TRAF/TANK, which results in its dissociation from TRAF2 and subsequent activation of NF-κB transcription through the classical IKK pathway
c35 cso30:c:InputProcess connector
c36 cso30:c:OutputProcess connector
c37 cso30:c:OutputProcess connector
p6_propro_p13
PMID: 17706453
TRAF3 and/or TRAF6 are also recruited to MAVS through a direct interaction with a TRAF-interaction motif within MAVS.
c38 cso30:c:InputProcess connector
c43 cso30:c:InputProcess connector
c39 cso30:c:OutputProcess connector
p14_propro_p14
PMID: 17706542
NEMO association with the adapter TANK facilitates the recruitment of TBK1 and IKKvar epsilon to the MAVS-TRAF complex and results in activation of TBK1 and IKKvar epsilon
PMID: 17706453,12133833,17468758
Physical association between TANK and NEMO suggest that the canonical IKK complex and the IKK-related kinases may exist as a physically associated signaling complex responsible for phosphorylation of additional transcription factors
PMID: 17706453
NEMO acts downstream of MAVS and RIG-I, and physically interacts with the TANK adapter to mediate recruitment of TBK1 and IKKvar epsilon to the RIG-IMAVS complex.
c40 cso30:c:InputProcess connector
c41 cso30:c:InputProcess connector
c42 cso30:c:OutputProcess connector
p15_propro_p15
PMID: 17706542
NEMO association with the adapter TANK facilitates the recruitment of TBK1 and IKKvar epsilon to the MAVS-TRAF complex and results in activation of TBK1 and IKK epsilon
c44 cso30:c:InputProcess connector
c45 cso30:c:InputProcess connector
c46 cso30:c:OutputProcess connector
p16_propro_p16
PMID: 17706542
NEMO association with the adapter TANK facilitates the recruitment of TBK1 and IKKvar epsilon to the MAVS-TRAF complex and results in activation of TBK1 and IKK epsilon
c47 cso30:c:InputProcess connector
c48 cso30:c:OutputProcess connector
p17_propro_p17
PMID: 17706453,15367631,14679297,16914100
Both TBK-1 and IKKvar epsilon directly phosphorylate IRF-3 and IRF-7 at key resides within their C-terminal signal-responsive domain in vitro and both kinases target identical serine residues
PMID: 17706543
Activated TBK1 and IKKvar epsilon phosphorylate IRF3 and IRF7, which provoke IFN expression and development of an antiviral state.
c49 cso30:c:InputAssociation connector
c50 cso30:c:InputProcess connector
c51 cso30:c:OutputProcess connector
p17_propro_p18
PMID: 17706453,15367631,14679297,16914100
Both TBK-1 and IKKvar epsilon directly phosphorylate IRF-3 and IRF-7 at key resides within their C-terminal signal-responsive domain in vitro and both kinases target identical serine residues
PMID: 17706543
Activated TBK1 and IKKvar epsilon phosphorylate IRF3 and IRF7, which provoke IFN expression and development of an antiviral state.
c52 cso30:c:InputAssociation connector
c53 cso30:c:InputProcess connector
c54 cso30:c:OutputProcess connector
p19_propro_p19
PMID: 17706453,10082512
Based on available biochemical data, a model for IRF-3 activation proposes that C-terminal phosphorylation induces a conformational change in IRF-3 that allows homo- and hetero-dimerization, nuclear localization, and association with the co-activator CBP/p300
c55 cso30:c:InputProcess connector
c56 cso30:c:OutputProcess connector
p20_propro_p20
PMID: 17706453,10082512
Based on available biochemical data, a model for IRF-3 activation proposes that C-terminal phosphorylation induces a conformational change in IRF-3 that allows homo- and hetero-dimerization, nuclear localization, and association with the co-activator CBP/p300
c57 cso30:c:InputProcess connector
c58 cso30:c:OutputProcess connector
p21_propro_p21
PMID: 17706453,10082512
Based on available biochemical data, a model for IRF-3 activation proposes that C-terminal phosphorylation induces a conformational change in IRF-3 that allows homo- and hetero-dimerization, nuclear localization, and association with the co-activator CBP/p300
c59 cso30:c:InputProcess connector
c60 cso30:c:InputProcess connector
c61 cso30:c:OutputProcess connector
p22_propro_p22
PMID: 17706453,17395583
Inactive IRF-3 constitutively shuttles into and out of the nucleus, whereas phosphorylation-dependent association with CBP/p300 retains IRF-3 in the nucleus and induces transcription of IFN-β and other genes
c62 cso30:c:InputAssociation connector
c63 cso30:c:OutputProcess connector
p15_propro_p23
PMID: 17706542
NEMO association with the adapter TANK facilitates the recruitment of TBK1 and IKKvar epsilon to the MAVS-TRAF complex and results in activation of TBK1 and IKK epsilon
c64 cso30:c:InputProcess connector
c65 cso30:c:InputProcess connector
c66 cso30:c:OutputProcess connector
p24_propro_p24
c67 cso30:c:InputProcess connector
c68 cso30:c:OutputProcess connector
p25_propro_p25
PMID: 17706453,17047224
Inducible activation of canonical NF-κB signaling requires phosphorylation of the IκB inhibitor by the 700900 kDa multi-protein canonical IKK complex composed of two catalytic kinase subunits, IKKgreek small letter alpha and IKKβ, and a non-enzymatic regulatory subunit NF-κB Essential Modulator (NEMO) or IKKγ
PMID: 17706543
MAVS-TRAF complexes also activate the canonical NEMO-IKKalpha-IKKβ complex which phosphorylates the inhibitory subunit IκBalpha, resulting in the release of NF-κB and activation of proinflammatory gene transcription.
c69 cso30:c:InputProcess connector
c70 cso30:c:InputAssociation connector
c71 cso30:c:OutputProcess connector
c72 cso30:c:OutputProcess connector
p26_propro_p26
PMID: 17706543
MAVS-TRAF complexes also activate the canonical NEMO-IKKalpha-IKKβ complex which phosphorylates the inhibitory subunit IκBalpha, resulting in the release of NF-κB and activation of proinflammatory gene transcription.
c73 cso30:c:InputAssociation connector
c74 cso30:c:OutputProcess connector
p27_propro_p27
PMID: 17706453
The structural and functional consequences of this phosphorylation remain to be determined, although it is suggested that IKKvar epsilon-dependent phosphorylation of STAT1 appears to guide the transcriptional machinery to a subset of ISGs required for the direct antiviral response, whereas the IKK-independent genes may function in regulating the IFN signaling required for integration of innate and adaptive immune systems.
c75 cso30:c:InputAssociation connector
c76 cso30:c:InputProcess connector
c77 cso30:c:OutputProcess connector
NF-kappaB_enti_MO000000058
NF-kappaB
IFIH1_enti_MO000103999
IFIH1
dsRNA_enti_MO000022224
dsRNA
DDX58:dsRNA_enti_e5
DDX58:dsRNA
DDX58_enti_MO000066987
DDX58
PolyI:C_enti_e6
PolyI:C
PolyI:C:IFIH1_enti_e10
PolyI:C:IFIH1
Efp_enti_MO000090351
Efp
DDX58:dsRNA:Efp_enti_e11
DDX58:dsRNA:Efp
DDX58 {ub}:dsRNA:Efp_enti_e12
DDX58 {ub}:dsRNA:Efp
MAVS_enti_MO000094908
MAVS
DDX58{ub}:dsRNA:Efp:MAVS_enti_e13
DDX58{ub}:dsRNA:Efp:MAVS
TRAF3_enti_MO000016963
TRAF3
DDX58{ub}:dsRNA:Efp:MAVS:TRAF3_enti_e14
DDX58{ub}:dsRNA:Efp:MAVS:TRAF3
IKK_enti_MO000000248
IKK
IKK-alpha_enti_MO000000210
IKK-alpha
IKK-beta_enti_MO000000211
IKK-beta
IKK-gamma_enti_MO000016599
IKK-gamma
TBK1_enti_MO000019331
TBK1
IKK-i_enti_MO000016608
IKK-i
NAP1_enti_e16
NAP1
NAP1:IKK-i:TBK1_enti_e17
NAP1:IKK-i:TBK1
TRAF2_enti_MO000000209
TRAF2
TANK:TRAF2_enti_e18
TANK:TRAF2
TANK:TRAF2:TBK1:IKK-i_enti_e15
TANK:TRAF2:TBK1:IKK-i
TANK{p}:TRAF2:TBK1:IKK-i_enti_e19
TANK{p}:TRAF2:TBK1:IKK-i
TANK{p}:TBK1:IKK-i_enti_e20
TANK{p}:TBK1:IKK-i
DDX58{ub}:dsRNA:Efp:MAVS:TRAF6_enti_e21
DDX58{ub}:dsRNA:Efp:MAVS:TRAF6
IKK:TANK{p}:TBK1:Ikk-i_enti_e22
IKK:TANK{p}:TBK1:Ikk-i
TRAF6_enti_MO000000212
TRAF6
DDX58{ub}:dsRNA:Efp:MAVS:TRAF3:IKK:TANK{p}:TBK1:IKK-i_enti_e23
DDX58{ub}:dsRNA:Efp:MAVS:TRAF3:IKK:TANK{p}:TBK1:IKK-i
DDX58{ub}:dsRNA:Efp:MAVS:TRAF3:IKK:TANK{p}:TBK1:IKK-i{active}_enti_e24
DDX58{ub}:dsRNA:Efp:MAVS:TRAF3:IKK:TANK{p}:TBK1:IKK-i{active}
IRF-3_enti_MO000007694
IRF-3
IRF-3{p}_enti_e25
IRF-3{p}
IRF-7_enti_MO000007702
IRF-7
IRF-7{active}_enti_e26
IRF-7{active}
IRF-3{p} dimer_enti_e27
IRF-3{p} dimer
IRF-3{p} dimer_enti_e28
IRF-3{p} dimer
CBP_enti_MO000099682
CBP
IRF-3{p}dimer:CBP_enti_e29
IRF-3{p}dimer:CBP
IFN-beta_enti_G010228
IFN-beta
DDX58{ub}:dsRNA:Efp:MAVS:TRAF6:IKK:TANK{p}:TBK1:IKK-i_enti_e30
DDX58{ub}:dsRNA:Efp:MAVS:TRAF6:IKK:TANK{p}:TBK1:IKK-i
DDX58{ub}:dsRNA:Efp:MAVS:TRAF6:IKK{active}:TANK{p}:TBK1:IKK-i_enti_e31
DDX58{ub}:dsRNA:Efp:MAVS:TRAF6:IKK{active}:TANK{p}:TBK1:IKK-i
NF-KappaB:IkappaB-alpha_enti_e32
NF-KappaB:IkappaB-alpha
IKappaB-alpha{p}_enti_e33
IKappaB-alpha{p}
proinflammatory genes_enti_e34
proinflammatory genes
STAT1_enti_MO000013119
STAT1
STAT1{p}_enti_e35
STAT1{p}