_enti_e7
_enti_e8
_enti_e9
_enti_e1
_enti_e10
_enti_e4
_enti_e3
_enti_e2
_enti_e55
_enti_e65
_enti_e20
_enti_e59
_enti_e53
_enti_e67
_enti_e66
_enti_e22
_enti_e21
_enti_e54
_enti_e52
_enti_e50
_enti_e56
_enti_e51
_enti_e24
_enti_e25
_enti_e23
_enti_e26
_enti_e58
_enti_e61
_enti_e57
_enti_e18
_enti_e62
_enti_e60
_enti_e19
g2_fact_g2
g1_fact_g14
g1_fact_g1
g2_fact_g12
g2_fact_g13
g1_fact_g6
g3_fact_g3
g1_fact_g5
g2_fact_g4
p1_propro_p1
PMID: 17395582
The virus-specific RNA species, dsRNA or 5'-triphosphate ssRNA, specifically binds to RIG-I through its RNA binding domain.
PMID: 17395582, 17190814
RNA binding requires intact helicase and C-terminal autorepression domains.
PMID: 17395582
Table2
c4 cso30:c:InputProcess connector
c5 cso30:c:InputProcess connector
c121 cso30:c:InputInhibitor connector
c123 cso30:c:InputInhibitor connector
c6 cso30:c:OutputProcess connector
p2_propro_p2
PMID: 17395582
The virus-specific RNA species, dsRNA or 5'-triphosphate ssRNA, specifically binds to RIG-I through its RNA binding domain.
PMID: 17395582, 17190814
RNA binding requires intact helicase and C-terminal autorepression domains.
c1 cso30:c:InputProcess connector
c2 cso30:c:InputProcess connector
c3 cso30:c:OutputProcess connector
p3_propro_p3
PMID: 17395582, 15208624, 15708988
RIG-I exhibits strong double-stranded RNA (dsRNA) binding activity in vitro. RIG-I selectively binds with poly(rI:rC), poly(rA:rU), and 5'- and 3'-untranslated regions of hepatitis C virus genomic RNA (which are predicted to form a secondary structure) but not with dsDNA, poly(rA), or yeast tRNA.
c7 cso30:c:InputProcess connector
c8 cso30:c:InputProcess connector
c9 cso30:c:OutputProcess connector
p4_propro_p4
PMID: 17395582, 15208624, 15708988
RIG-I exhibits strong double-stranded RNA (dsRNA) binding activity in vitro. RIG-I selectively binds with poly(rI:rC), poly(rA:rU), and 5'- and 3'-untranslated regions of hepatitis C virus genomic RNA (which are predicted to form a secondary structure) but not with dsDNA, poly(rA), or yeast tRNA.
c10 cso30:c:InputProcess connector
c11 cso30:c:InputProcess connector
c12 cso30:c:OutputProcess connector
p5_propro_p5
PMID: 17395582, 16127453, 16125763, 16153868
This association and ATP binding to the helicase domain change RIG-I conformation to release CARD for relaying signaling to the downstream molecule (another CARD-containing molecule, IPS-1 (alternatively termed MAVS, VISA, and Cardif)).
PMID: 17395582
Table2
c14 cso30:c:InputProcess connector
c18 cso30:c:InputProcess connector
c122 cso30:c:InputInhibitor connector
c15 cso30:c:OutputProcess connector
p6_propro_p6
PMID: 17395582, 16127453, 16125763, 16153868
This association and ATP binding to the helicase domain change RIG-I conformation to release CARD for relaying signaling to the downstream molecule (another CARD-containing molecule, IPS-1 (alternatively termed MAVS, VISA, and Cardif)).
PMID: 17395582
Lys-270 is supposed to be a critical motif for ATP binding within the helicase domain, and in the case of other DExH/D helicases, this motif is crucial for its helicase (unwinding dsRNA) activity.
c13 cso30:c:InputProcess connector
c16 cso30:c:InputProcess connector
c17 cso30:c:OutputProcess connector
p7_propro_p7
PMID: 17395582, 16785313, 16713980
MDA5 and RIG-I, which sense a distinct set of viruses (below), commonly transmit signals to IPS-1; thus IPS-1/ fibroblasts are unresponsive to either set of viruses.
PMID: 17395582
Table2
c19 cso30:c:InputProcess connector
c20 cso30:c:InputProcess connector
c124 cso30:c:InputInhibitor connector
c21 cso30:c:OutputProcess connector
p8_propro_p8
PMID: 17395582, 16785313, 16713980
MDA5 and RIG-I, which sense a distinct set of viruses (below), commonly transmit signals to IPS-1; thus IPS-1/ fibroblasts are unresponsive to either set of viruses.
c22 cso30:c:InputProcess connector
c23 cso30:c:InputProcess connector
c24 cso30:c:OutputProcess connector
p9_propro_p9
PMID: 17395582, 16858409, 15210743, 15210742
The latter involves TNF (tumor necrosis factor) receptor-associating factor 3 (TRAF3) (17) and the protein kinase, I{kappa}B kinase-i (IKK-i ({epsilon})) or TANK-binding kinase-1 (TBK-1) (18, 19), which is responsible for the activation of IRF-3 and -7.
c25 cso30:c:InputProcess connector
c27 cso30:c:InputProcess connector
c29 cso30:c:OutputProcess connector
p10_propro_p10
PMID: 17395582, 16858409, 15210743, 15210742
The latter involves TNF (tumor necrosis factor) receptor-associating factor 3 (TRAF3) (17) and the protein kinase, I{kappa}B kinase-i (IKK-i ({epsilon})) or TANK-binding kinase-1 (TBK-1) (18, 19), which is responsible for the activation of IRF-3 and -7.
c26 cso30:c:InputProcess connector
c28 cso30:c:InputProcess connector
c30 cso30:c:OutputProcess connector
p11_propro_p11
PMID: 17395582, 16858409, 15210743, 15210742
The latter involves TNF (tumor necrosis factor) receptor-associating factor 3 (TRAF3) (17) and the protein kinase, I{kappa}B kinase-i (IKK-i ({epsilon})) or TANK-binding kinase-1 (TBK-1) (18, 19), which is responsible for the activation of IRF-3 and -7.
c31 cso30:c:InputProcess connector
c35 cso30:c:InputProcess connector
c33 cso30:c:InputProcess connector
c37 cso30:c:OutputProcess connector
p12_propro_p12
PMID: 17395582, 16858409, 15210743, 15210742
The latter involves TNF (tumor necrosis factor) receptor-associating factor 3 (TRAF3) (17) and the protein kinase, I{kappa}B kinase-i (IKK-i ({epsilon})) or TANK-binding kinase-1 (TBK-1) (18, 19), which is responsible for the activation of IRF-3 and -7.
c32 cso30:c:InputProcess connector
c34 cso30:c:InputProcess connector
c36 cso30:c:InputProcess connector
c38 cso30:c:OutputProcess connector
p13_propro_p13
PMID: 17395582, 16858409, 15210743, 15210742
The latter involves TNF (tumor necrosis factor) receptor-associating factor 3 (TRAF3) (17) and the protein kinase, I{kappa}B kinase-i (IKK-i ({epsilon})) or TANK-binding kinase-1 (TBK-1) (18, 19), which is responsible for the activation of IRF-3 and -7.
c39 cso30:c:InputProcess connector
c47 cso30:c:InputAssociation connector
c40 cso30:c:OutputProcess connector
p14_propro_p14
PMID: 17395582, 16858409, 15210743, 15210742
The latter involves TNF (tumor necrosis factor) receptor-associating factor 3 (TRAF3) (17) and the protein kinase, I{kappa}B kinase-i (IKK-i ({epsilon})) or TANK-binding kinase-1 (TBK-1) (18, 19), which is responsible for the activation of IRF-3 and -7.
c41 cso30:c:InputProcess connector
c49 cso30:c:InputAssociation connector
c42 cso30:c:OutputProcess connector
p15_propro_p15
PMID: 17395582, 16858409, 15210743, 15210742
The latter involves TNF (tumor necrosis factor) receptor-associating factor 3 (TRAF3) (17) and the protein kinase, I{kappa}B kinase-i (IKK-i ({epsilon})) or TANK-binding kinase-1 (TBK-1) (18, 19), which is responsible for the activation of IRF-3 and -7.
c43 cso30:c:InputProcess connector
c50 cso30:c:InputAssociation connector
c44 cso30:c:OutputProcess connector
p16_propro_p16
PMID: 17395582, 16858409, 15210743, 15210742
The latter involves TNF (tumor necrosis factor) receptor-associating factor 3 (TRAF3) (17) and the protein kinase, I{kappa}B kinase-i (IKK-i ({epsilon})) or TANK-binding kinase-1 (TBK-1) (18, 19), which is responsible for the activation of IRF-3 and -7.
c45 cso30:c:InputProcess connector
c48 cso30:c:InputAssociation connector
c46 cso30:c:OutputProcess connector
p17_propro_p17
PMID: 17395582
The signal is branched at IPS-1, resulting in the activation of NF-kappaB and IRF-3 and -7.
c51 cso30:c:InputProcess connector
c55 cso30:c:InputAssociation connector
c52 cso30:c:OutputProcess connector
p18_propro_p18
PMID: 17395582
The signal is branched at IPS-1, resulting in the activation of NF-kappaB and IRF-3 and -7.
c53 cso30:c:InputProcess connector
c56 cso30:c:InputAssociation connector
c54 cso30:c:OutputProcess connector
p19_propro_p19
PMID: 17395582
The signal is branched at IPS-1, resulting in the activation of NF-kappaB and IRF-3 and -7.
c57 cso30:c:InputProcess connector
c59 cso30:c:InputAssociation connector
c58 cso30:c:OutputProcess connector
p20_propro_p20
PMID: 17395582, 16116171, 16210631, 17020950
LGP2 lacks CARD, suggesting that this helicase is incapable of transmitting a positive signal. Overexpression of LGP2 in cell culture results in the dominant inhibition of virus-induced activation of IFN genes, suggesting its role as a negative regulator; however, its role in vivo is not established.
PMID: 17395582
Analyses of RIG-I/ fibroblasts and conventional dendritic cells (cDCs) showed that RIG-I is essential in Newcastle disease virus (NDV)-induced IFN production.
c60 cso30:c:InputAssociation connector
c64 cso30:c:InputInhibitor connector
c62 cso30:c:OutputProcess connector
p21_propro_p21
PMID: 17395582, 16116171, 16210631, 17020950
LGP2 lacks CARD, suggesting that this helicase is incapable of transmitting a positive signal. Overexpression of LGP2 in cell culture results in the dominant inhibition of virus-induced activation of IFN genes, suggesting its role as a negative regulator; however, its role in vivo is not established.
PMID: 17395582
Analyses of RIG-I/ fibroblasts and conventional dendritic cells (cDCs) showed that RIG-I is essential in Newcastle disease virus (NDV)-induced IFN production.
c61 cso30:c:InputAssociation connector
c65 cso30:c:InputInhibitor connector
c63 cso30:c:OutputProcess connector
p22_propro_p22
PMID: 17395582, 15585605, 16932750
pDCs adopt a distinct signaling cascade to produce high levels of IFN-alpha and sense viral infection by TLR7/8 and TLR9, activating signaling cascades MyD88, IRAK1/4, TRAF3/6, IKK-alpha, and IRF-7.
c68 cso30:c:InputProcess connector
c70 cso30:c:InputAssociation connector
c69 cso30:c:OutputProcess connector
p23_propro_p23
PMID: 17395582, 15585605, 16932750
pDCs adopt a distinct signaling cascade to produce high levels of IFN-alpha and sense viral infection by TLR7/8 and TLR9, activating signaling cascades MyD88, IRAK1/4, TRAF3/6, IKK-alpha, and IRF-7.
c66 cso30:c:InputProcess connector
c71 cso30:c:InputAssociation connector
c67 cso30:c:OutputProcess connector
p25_propro_p25
PMID: 17395582, 15585605, 16932750
pDCs adopt a distinct signaling cascade to produce high levels of IFN-alpha and sense viral infection by TLR7/8 and TLR9, activating signaling cascades MyD88, IRAK1/4, TRAF3/6, IKK-alpha, and IRF-7.
c72 cso30:c:InputProcess connector
c74 cso30:c:InputAssociation connector
c73 cso30:c:OutputProcess connector
p26_propro_p26
PMID: 17395582, 15585605, 16932750
pDCs adopt a distinct signaling cascade to produce high levels of IFN-alpha and sense viral infection by TLR7/8 and TLR9, activating signaling cascades MyD88, IRAK1/4, TRAF3/6, IKK-alpha, and IRF-7.
c75 cso30:c:InputProcess connector
c80 cso30:c:InputAssociation connector
c76 cso30:c:OutputProcess connector
p24_propro_p24
PMID: 17395582, 15585605, 16932750
pDCs adopt a distinct signaling cascade to produce high levels of IFN-alpha and sense viral infection by TLR7/8 and TLR9, activating signaling cascades MyD88, IRAK1/4, TRAF3/6, IKK-alpha, and IRF-7.
c77 cso30:c:InputProcess connector
c79 cso30:c:InputAssociation connector
c78 cso30:c:OutputProcess connector
p27_propro_p27
PMID: 17395582, 15585605, 16932750
pDCs adopt a distinct signaling cascade to produce high levels of IFN-alpha and sense viral infection by TLR7/8 and TLR9, activating signaling cascades MyD88, IRAK1/4, TRAF3/6, IKK-alpha, and IRF-7.
c81 cso30:c:InputProcess connector
c85 cso30:c:InputAssociation connector
c82 cso30:c:OutputProcess connector
p28_propro_p28
PMID: 17395582, 15585605, 16932750
pDCs adopt a distinct signaling cascade to produce high levels of IFN-alpha and sense viral infection by TLR7/8 and TLR9, activating signaling cascades MyD88, IRAK1/4, TRAF3/6, IKK-alpha, and IRF-7.
c83 cso30:c:InputProcess connector
c86 cso30:c:InputAssociation connector
c84 cso30:c:OutputProcess connector
p29_propro_p29
PMID: 17395582, 15585605, 16932750
pDCs adopt a distinct signaling cascade to produce high levels of IFN-alpha and sense viral infection by TLR7/8 and TLR9, activating signaling cascades MyD88, IRAK1/4, TRAF3/6, IKK-alpha, and IRF-7.
c87 cso30:c:InputProcess connector
c89 cso30:c:InputAssociation connector
c88 cso30:c:OutputProcess connector
p30_propro_p30
PMID: 17395582, 15585605
It has been known that dsRNA activates TLR3 in endosome and signals through TIR domain-containing adaptor inducing IFN-beta (TRIF)/TIR-containing adaptor molecule-1 (TICAM1) resulting in the activation of kinases (TBK-1 or IKK-i) and transcription factors (IRF-3 and -7 and NF-kappaB).
c90 cso30:c:InputProcess connector
c91 cso30:c:InputProcess connector
c92 cso30:c:OutputProcess connector
p31_propro_p31
PMID: 17395582, 15585605
It has been known that dsRNA activates TLR3 in endosome and signals through TIR domain-containing adaptor inducing IFN-beta (TRIF)/TIR-containing adaptor molecule-1 (TICAM1) resulting in the activation of kinases (TBK-1 or IKK-i) and transcription factors (IRF-3 and -7 and NF-kappaB).
c93 cso30:c:InputProcess connector
c94 cso30:c:InputProcess connector
c95 cso30:c:OutputProcess connector
p32_propro_p32
PMID: 17395582, 15585605
It has been known that dsRNA activates TLR3 in endosome and signals through TIR domain-containing adaptor inducing IFN-beta (TRIF)/TIR-containing adaptor molecule-1 (TICAM1) resulting in the activation of kinases (TBK-1 or IKK-i) and transcription factors (IRF-3 and -7 and NF-kappaB).
c96 cso30:c:InputProcess connector
c98 cso30:c:InputAssociation connector
c97 cso30:c:OutputProcess connector
p33_propro_p33
PMID: 17395582, 15585605
It has been known that dsRNA activates TLR3 in endosome and signals through TIR domain-containing adaptor inducing IFN-beta (TRIF)/TIR-containing adaptor molecule-1 (TICAM1) resulting in the activation of kinases (TBK-1 or IKK-i) and transcription factors (IRF-3 and -7 and NF-kappaB).
c99 cso30:c:InputProcess connector
c104 cso30:c:InputAssociation connector
c100 cso30:c:OutputProcess connector
p34_propro_p34
PMID: 17395582, 15585605
It has been known that dsRNA activates TLR3 in endosome and signals through TIR domain-containing adaptor inducing IFN-beta (TRIF)/TIR-containing adaptor molecule-1 (TICAM1) resulting in the activation of kinases (TBK-1 or IKK-i) and transcription factors (IRF-3 and -7 and NF-kappaB).
c101 cso30:c:InputProcess connector
c103 cso30:c:InputAssociation connector
c102 cso30:c:OutputProcess connector
p35_propro_p35
PMID: 17395582, 15585605
It has been known that dsRNA activates TLR3 in endosome and signals through TIR domain-containing adaptor inducing IFN-beta (TRIF)/TIR-containing adaptor molecule-1 (TICAM1) resulting in the activation of kinases (TBK-1 or IKK-i) and transcription factors (IRF-3 and -7 and NF-kappaB).
c105 cso30:c:InputProcess connector
c107 cso30:c:InputAssociation connector
c106 cso30:c:OutputProcess connector
p36_propro_p36
PMID: 17395582
When poly(rI:rC) is injected into mice intravenously, IFN-beta is strictly produced in a MDA5-dependent manner (below), but the TLR-TRIF pathway is dispensable.
c108 cso30:c:InputProcess connector
c109 cso30:c:InputProcess connector
c110 cso30:c:OutputProcess connector
p37_propro_p37
PMID: 17395582
When poly(rI:rC) is injected into mice intravenously, IFN-beta is strictly produced in a MDA5-dependent manner (below), but the TLR-TRIF pathway is dispensable.
c111 cso30:c:InputAssociation connector
c112 cso30:c:OutputProcess connector
p38_propro_p38
PMID: 17395582, 16625202
However, production of IL-8 and IL-12 p40 requires TRIF in addition to MDA5; IL-12 p40 is particularly largely TRIF-dependent.
c114 cso30:c:InputAssociation connector
c113 cso30:c:OutputProcess connector
p39_propro_p39
PMID: 17395582, 16625202
However, production of IL-8 and IL-12 p40 requires TRIF in addition to MDA5; IL-12 p40 is particularly largely TRIF-dependent.
c117 cso30:c:InputAssociation connector
c115 cso30:c:OutputProcess connector
p40_propro_p40
PMID: 17395582, 16125763, 16585524, 16731946
NS3/4A of hepatitis C virus inactivates IPS-1 by its protease activity.
c118 cso30:c:InputProcess connector
c120 cso30:c:InputAssociation connector
c119 cso30:c:OutputProcess connector
p41_propro_p41
PMID: 17395582, 16625202
However, production of IL-8 and IL-12 p40 requires TRIF in addition to MDA5; IL-12 p40 is particularly largely TRIF-dependent.
c116 cso30:c:InputAssociation connector
c125 cso30:c:OutputProcess connector
RIG-1_enti_e5
RIG-1
dsRNA_enti_e6
dsRNA
dsRNA: RIG-1_enti_e11
dsRNA: RIG-1
5'-triphosphate ssRNA_enti_e12
5'-triphosphate ssRNA
5'-triphosphate ssRNA: RIG-1_enti_e13
5'-triphosphate ssRNA: RIG-1
poly(rI:rC)_enti_e14
poly(rI:rC)
poly(rA:rU)_enti_e15
poly(rA:rU)
poly(rI:rC): RIG-1_enti_e16
poly(rI:rC): RIG-1
poly(rA:rU): RIG-1_enti_e17
poly(rA:rU): RIG-1
MDA5_enti_e27
MDA5
dsRNA: MDA5_enti_e28
dsRNA: MDA5
IPS-1_enti_e29
IPS-1
dsRNA: RIG-1: IPS-1_enti_e30
dsRNA: RIG-1: IPS-1
ATP_enti_e31
ATP
dsRNA: RIG-1: ATP_enti_e32
dsRNA: RIG-1: ATP
dsRNA: MDA5: IPS-1_enti_e33
dsRNA: MDA5: IPS-1
TRAF3_enti_e34
TRAF3
dsRNA: MDA5: IPS-1: TRAF3_enti_e35
dsRNA: MDA5: IPS-1: TRAF3
dsRNA: RIG-1: IPS-1: TRAF3_enti_e36
dsRNA: RIG-1: IPS-1: TRAF3
IKK-i_enti_e37
IKK-i
TBK-1_enti_e38
TBK-1
dsRNA: MDA5: IPS-1: TRAF3: IKK-i: TBK-1_enti_e39
dsRNA: MDA5: IPS-1: TRAF3: IKK-i: TBK-1
dsRNA: RIG-1: IPS-1: TRAF3: IKK-i: TBK-1_enti_e40
dsRNA: RIG-1: IPS-1: TRAF3: IKK-i: TBK-1
IRF-3_enti_e41
IRF-3
IRF-7_enti_e42
IRF-7
IRF-3{activated}_enti_e43
IRF-3{activated}
IRF-7{activated}_enti_e44
IRF-7{activated}
IKK complex_enti_e45
IKK complex
IKK complex{activated}_enti_e46
IKK complex{activated}
NF-kappaB_enti_e47
NF-kappaB
NF-kappaB{activated}_enti_e48
NF-kappaB{activated}
IFN_enti_e49
IFN
LGP2_enti_e63
LGP2
ligand: TLR7/TLR8_enti_e68
ligand: TLR7/TLR8
ligand: TLR9_enti_e70
ligand: TLR9
TLR3_enti_e71
TLR3
dsRNA: TLR3_enti_e72
dsRNA: TLR3
MyD88_enti_e64
MyD88
MyD88{activated}_enti_e69
MyD88{activated}
IRAK-1: IRAK4_enti_e73
IRAK-1: IRAK4
IRAK-1: IRAK4{activated}_enti_e74
IRAK-1: IRAK4{activated}
TRAF6_enti_e75
TRAF6
TRAF6{activated}_enti_e76
TRAF6{activated}
TRAF3_enti_e77
TRAF3
TRAF3{activated}_enti_e78
TRAF3{activated}
IKK-alpha_enti_e79
IKK-alpha
IKK-alpha{activated}_enti_e80
IKK-alpha{activated}
TRIF_enti_e81
TRIF
dsRNA: TLR3: TRIF_enti_e82
dsRNA: TLR3: TRIF
IKK-i: TBK-1_enti_e83
IKK-i: TBK-1
IKK-i: TBK-1{activated}_enti_e84
IKK-i: TBK-1{activated}
poly(rI:rC): MDA-5_enti_e85
poly(rI:rC): MDA-5
IFN-beta_enti_e86
IFN-beta
IL-12p40_enti_e87
IL-12p40
IL-8_enti_e88
IL-8
NS3/4A_enti_e89
NS3/4A
protein remnant_enti_e90
NS1_enti_e91
NS1
VP35_enti_e92
VP35
V protein_enti_e93
V protein