_enti_e7
_enti_e8
_enti_e9
_enti_e1
_enti_e3
_enti_e4
_enti_e2
_enti_e55
_enti_e53
_enti_e59
_enti_e52
_enti_e50
_enti_e56
_enti_e54
_enti_e51
_enti_e57
_enti_e61
_enti_e58
_enti_e62
_enti_e60
g1_fact_g1
g2_fact_g12
g2_fact_g13
g1_fact_g14
p1_propro_p1
PMID: 15283983,9041265,8591843
IFN-a also
confers immunomodulatory benefits. For example, binding
to its cognate cell-surface receptor on immune cells can
result in: a
reduction in inflammation by inhibiting production of
IL-1, IL-8 and tumor necrosis factor (TNF)-a
c1 cso30:c:InputProcess connector
c2 cso30:c:InputProcess connector
c3 cso30:c:OutputProcess connector
p2_propro_p2
PMID: 15283983,9041265,8591843
IFN-a also
confers immunomodulatory benefits. For example, binding
to its cognate cell-surface receptor on immune cells can
result in: a
reduction in inflammation by inhibiting production of
IL-1, IL-8 and tumor necrosis factor (TNF)-a
c4 cso30:c:InputAssociation connector
c10 cso30:c:InputInhibitor connector
c7 cso30:c:OutputProcess connector
p2_propro_p3
PMID: 15283983,9041265,8591843
IFN-a also
confers immunomodulatory benefits. For example, binding
to its cognate cell-surface receptor on immune cells can
result in: a
reduction in inflammation by inhibiting production of
IL-1, IL-8 and tumor necrosis factor (TNF)-a
c5 cso30:c:InputAssociation connector
c11 cso30:c:InputInhibitor connector
c8 cso30:c:OutputProcess connector
p2_propro_p4
PMID: 15283983,9041265,8591843
IFN-a also
confers immunomodulatory benefits. For example, binding
to its cognate cell-surface receptor on immune cells can
result in: a
reduction in inflammation by inhibiting production of
IL-1, IL-8 and tumor necrosis factor (TNF)-a
c6 cso30:c:InputAssociation connector
c12 cso30:c:InputInhibitor connector
c9 cso30:c:OutputProcess connector
p5_propro_p5
PMID:15283983,9857039,11427497
treatment ofcultured mammalian cells with IFN-a or TNF-a results in induction of SOCS1
and SOCS3
c13 cso30:c:InputProcess connector
c14 cso30:c:InputProcess connector
c15 cso30:c:OutputProcess connector
p6_propro_p6
PMID:15283983,9857039,11427497
treatment ofcultured mammalian cells with IFN-a or TNF-a results in induction of SOCS1
and SOCS3
c16 cso30:c:InputAssociation connector
c17 cso30:c:OutputProcess connector
p6_propro_p7
PMID: 15283983
TNF-a stimulates expression of SOCS3 and SHP2, which bind to the JAK IFN
receptor complex.
c18 cso30:c:InputAssociation connector
c19 cso30:c:OutputProcess connector
p8_propro_p8
PMID:15283983,9857039,11427497
treatment ofcultured mammalian cells with IFN-a or TNF-a results in induction of SOCS1
and SOCS3
c20 cso30:c:InputAssociation connector
c21 cso30:c:OutputProcess connector
p8_propro_p9
PMID:15283983,9857039,11427497
treatment ofcultured mammalian cells with IFN-a or TNF-a results in induction of SOCS1
and SOCS3
c22 cso30:c:InputAssociation connector
c23 cso30:c:OutputProcess connector
p6_propro_p10
PMID: 15283983
TNF-a stimulates expression of SOCS3 and SHP2, which bind to the JAK IFN
receptor complex.
c24 cso30:c:InputAssociation connector
c25 cso30:c:OutputProcess connector
p11_propro_p11
PMID: 15283983
NS5A binds to PKR in a region that overlaps the ISDR
domain, and would be expected to suppress its function
in vivo.
c26 cso30:c:InputProcess connector
c27 cso30:c:InputProcess connector
c28 cso30:c:OutputProcess connector
p12_propro_p12
PMID:15283983
Specifically, the
signal transducer and activator of transcription (STAT)
family of latent cytoplasmic transcription factors become
tyrosine phosphorylated by the Janus family of tyrosine
kinases (JAK) following binding of IFNs to their cognate
multi-subunit transmembrane receptor
PMID:15283983
This interaction prevents STAT activation and translocation to
the nucleus, where it would otherwise induce antiviral response genes containing
an ISRE.
PMID: 15283983,9857039,11427497
treatment ofcultured mammalian cells with IFN-a or TNF-a results in induction of SOCS1
and SOCS3, the only two SOCS proteins reported
to inhibit IFN-mediated antiviral and antiproliferative
activities
PMID: 15283983,12551851
Consistent with this observation, an initial
report by Bode et al. claimed that overexpression of the
HCV core protein inhibits IFN-a-induced tyrosine phosphorylation
and activation of STAT1 in hepatic cells.
c32 cso30:c:InputAssociation connector
c33 cso30:c:InputProcess connector
c54 cso30:c:InputInhibitor connector
c60 cso30:c:InputInhibitor connector
c75 cso30:c:InputInhibitor connector
c76 cso30:c:InputInhibitor connector
c34 cso30:c:OutputProcess connector
p13_propro_p13
PMID: 15283983
TNF-a stimulates expression of SOCS3 and SHP2, which bind to the JAK IFN
receptor complex.
c29 cso30:c:InputProcess connector
c30 cso30:c:InputProcess connector
c31 cso30:c:OutputProcess connector
p14_propro_p14
PMID:15283983
This interaction prevents STAT activation and translocation to
the nucleus, where it would otherwise induce antiviral response genes containing
an ISRE.
c35 cso30:c:InputProcess connector
c36 cso30:c:OutputProcess connector
p15_propro_p15
PMID: 15283983
Specifically, they (STAT)
recognize DNA promoter elements to modulate type I IFN
(IFN-a and IFN-b) genes selectively, and also recognize
the interferon-stimulated response element (ISRE) in
some ISGs, leading to induction of an antiviral state.
PMID:15283983
This interaction prevents STAT activation and translocation to
the nucleus, where it would otherwise induce antiviral response genes containing
an ISRE.
c37 cso30:c:InputProcess connector
c38 cso30:c:InputProcess connector
c39 cso30:c:OutputProcess connector
p16_propro_p16
PMID: 15283983
Specifically, they (STAT)
recognize DNA promoter elements to modulate type I IFN
(IFN-a and IFN-b) genes selectively, and also recognize
the interferon-stimulated response element (ISRE) in
some ISGs, leading to induction of an antiviral state.
PMID:15283983
This interaction prevents STAT activation and translocation to
the nucleus, where it would otherwise induce antiviral response genes containing
an ISRE.
c40 cso30:c:InputAssociation connector
c41 cso30:c:OutputProcess connector
p17_propro_p17
PMID: 15283983
Specifically, they (STAT)
recognize DNA promoter elements to modulate type I IFN
(IFN-a and IFN-b) genes selectively, and also recognize
the interferon-stimulated response element (ISRE) in
some ISGs, leading to induction of an antiviral state.
c42 cso30:c:InputAssociation connector
c43 cso30:c:OutputProcess connector
p17_propro_p18
PMID: 15283983
Specifically, they (STAT)
recognize DNA promoter elements to modulate type I IFN
(IFN-a and IFN-b) genes selectively, and also recognize
the interferon-stimulated response element (ISRE) in
some ISGs, leading to induction of an antiviral state.
c44 cso30:c:InputAssociation connector
c45 cso30:c:OutputProcess connector
p19_propro_p19
PMID: 15283983
Similar to NS5A, the HCV E2 protein was reported to
contain a double-stranded (ds)RNA-activated protein
kinase eukaryotic initiation factor 2a (PKR-eIF2a) homology
domain, which might be capable of interacting with
and inactivating PKR.
c46 cso30:c:InputProcess connector
c47 cso30:c:InputProcess connector
c48 cso30:c:OutputProcess connector
p20_propro_p20
PMID: 15283983
TNF-a stimulates expression of SOCS3 and SHP2, which bind to the JAK IFN
receptor complex.
c49 cso30:c:InputAssociation connector
c50 cso30:c:OutputProcess connector
p13_propro_p21
PMID: 15283983
TNF-a stimulates expression of SOCS3 and SHP2, which bind to the JAK IFN
receptor complex.
c51 cso30:c:InputProcess connector
c52 cso30:c:InputProcess connector
c53 cso30:c:OutputProcess connector
p20_propro_p22
PMID: 15283983
TNF-a stimulates expression of SOCS3 and SHP2, which bind to the JAK IFN
receptor complex.
c55 cso30:c:InputAssociation connector
c56 cso30:c:OutputProcess connector
p13_propro_p23
PMID: 15283983
TNF-a stimulates expression of SOCS3 and SHP2, which bind to the JAK IFN
receptor complex.
c57 cso30:c:InputProcess connector
c58 cso30:c:InputProcess connector
c59 cso30:c:OutputProcess connector
p24_propro_p24
PMID: 15283983,10048763
Characterization
of IRF-3 showed regulatory activity by binding to the ISRE
of ISG15 and interaction with the CBP/p300 coactivator
c62 cso30:c:InputProcess connector
c110 cso30:c:InputProcess connector
c63 cso30:c:OutputProcess connector
p25_propro_p25
PMID: 15283983,10048763
Characterization
of IRF-3 showed regulatory activity by binding to the ISRE
of ISG15 and interaction with the CBP/p300 coactivator
c64 cso30:c:InputProcess connector
c65 cso30:c:InputProcess connector
c66 cso30:c:OutputProcess connector
p25_propro_p26
PMID: 15283983,10048763
Characterization
of IRF-3 showed regulatory activity by binding to the ISRE
of ISG15 and interaction with the CBP/p300 coactivator
c67 cso30:c:InputProcess connector
c68 cso30:c:InputProcess connector
c69 cso30:c:OutputProcess connector
p27_propro_p27
PMID: 15283983,9857039,11427497
treatment ofcultured mammalian cells with IFN-a or TNF-a results in induction of SOCS1
and SOCS3, the only two SOCS proteins reported
to inhibit IFN-mediated antiviral and antiproliferative
activities
c70 cso30:c:InputAssociation connector
c71 cso30:c:OutputProcess connector
p28_propro_p28
PMID: 15283983,9857039,11427497
treatment ofcultured mammalian cells with IFN-a or TNF-a results in induction of SOCS1
and SOCS3, the only two SOCS proteins reported
to inhibit IFN-mediated antiviral and antiproliferative
activities
c72 cso30:c:InputProcess connector
c73 cso30:c:InputProcess connector
c74 cso30:c:OutputProcess connector
p29_propro_p29
PMID: 15283983,14644140,10453004,11390452,12433373
SOCS1 and SOCS3 expression can be induced by various
cytokines, and can also be
induced by, and negatively regulate, LPS and CpG DNA,
which are conserved bacterial components characterized
as structural correlates of PAMP
c77 cso30:c:InputProcess connector
c78 cso30:c:InputProcess connector
c79 cso30:c:OutputProcess connector
p30_propro_p30
PMID: 15283983,14644140,10453004,11390452,12433373
SOCS1 and SOCS3 expression can be induced by various
cytokines, and can also be
induced by, and negatively regulate, LPS and CpG DNA,
which are conserved bacterial components characterized
as structural correlates of PAMP
c80 cso30:c:InputAssociation connector
c81 cso30:c:OutputProcess connector
p30_propro_p31
PMID: 15283983,14644140,10453004,11390452,12433373
SOCS1 and SOCS3 expression can be induced by various
cytokines, and can also be
induced by, and negatively regulate, LPS and CpG DNA,
which are conserved bacterial components characterized
as structural correlates of PAMP
c82 cso30:c:InputAssociation connector
c83 cso30:c:OutputProcess connector
p30_propro_p32
PMID: 15283983,14644140,10453004,11390452,12433373
SOCS1 and SOCS3 expression can be induced by various
cytokines, and can also be
induced by, and negatively regulate, LPS and CpG DNA,
which are conserved bacterial components characterized
as structural correlates of PAMP
c90 cso30:c:InputAssociation connector
c84 cso30:c:OutputProcess connector
p30_propro_p33
PMID: 15283983,14644140,10453004,11390452,12433373
SOCS1 and SOCS3 expression can be induced by various
cytokines, and can also be
induced by, and negatively regulate, LPS and CpG DNA,
which are conserved bacterial components characterized
as structural correlates of PAMP
c89 cso30:c:InputAssociation connector
c85 cso30:c:OutputProcess connector
p29_propro_p34
PMID: 15283983,14644140,10453004,11390452,12433373
SOCS1 and SOCS3 expression can be induced by various
cytokines, and can also be
induced by, and negatively regulate, LPS and CpG DNA,
which are conserved bacterial components characterized
as structural correlates of PAMP
c86 cso30:c:InputProcess connector
c87 cso30:c:InputProcess connector
c88 cso30:c:OutputProcess connector
p35_propro_p35
PMID: 15283983,14630206
This
same pathway can be induced by activation of other
cytokine receptors including those for IL-6 and IL-10
c91 cso30:c:InputProcess connector
c92 cso30:c:InputProcess connector
c93 cso30:c:OutputProcess connector
p35_propro_p36
PMID: 15283983,14630206
This
same pathway can be induced by activation of other
cytokine receptors including those for IL-6 and IL-10
c94 cso30:c:InputProcess connector
c95 cso30:c:InputProcess connector
c96 cso30:c:OutputProcess connector
p37_propro_p37
PMID: 15283983,14630206
This
same pathway can be induced by activation of other
cytokine receptors including those for IL-6 and IL-10
c97 cso30:c:InputAssociation connector
c98 cso30:c:InputProcess connector
c112 cso30:c:InputInhibitor connector
c113 cso30:c:InputInhibitor connector
c115 cso30:c:InputInhibitor connector
c99 cso30:c:OutputProcess connector
p35_propro_p38
PMID: 15283983,14630206
This
same pathway can be induced by activation of other
cytokine receptors including those for IL-6 and IL-10
c100 cso30:c:InputProcess connector
c101 cso30:c:InputProcess connector
c102 cso30:c:OutputProcess connector
p35_propro_p39
PMID: 15283983,14630206
This
same pathway can be induced by activation of other
cytokine receptors including those for IL-6 and IL-10
c103 cso30:c:InputProcess connector
c104 cso30:c:InputProcess connector
c105 cso30:c:OutputProcess connector
p37_propro_p40
PMID: 15283983,14630206
This
same pathway can be induced by activation of other
cytokine receptors including those for IL-6 and IL-10
c106 cso30:c:InputAssociation connector
c107 cso30:c:InputProcess connector
c111 cso30:c:InputInhibitor connector
c114 cso30:c:InputInhibitor connector
c116 cso30:c:InputInhibitor connector
c108 cso30:c:OutputProcess connector
p41_propro_p41
PMID: 15283983,10048763
Characterization
of IRF-3 showed regulatory activity by binding to the ISRE
of ISG15 and interaction with the CBP/p300 coactivator
c61 cso30:c:InputProcess connector
c109 cso30:c:OutputProcess connector
p42_propro_p42
c117 cso30:c:InputProcess connector
p43_propro_p43
c123 cso30:c:InputProcess connector
p44_propro_p44
c121 cso30:c:InputProcess connector
p45_propro_p45
c122 cso30:c:InputProcess connector
p46_propro_p46
c118 cso30:c:InputProcess connector
p47_propro_p47
c124 cso30:c:InputProcess connector
p48_propro_p48
c125 cso30:c:InputProcess connector
p49_propro_p49
c126 cso30:c:InputProcess connector
p50_propro_p50
c127 cso30:c:InputProcess connector
p51_propro_p51
c128 cso30:c:InputProcess connector
p52_propro_p52
c129 cso30:c:InputProcess connector
p53_propro_p53
c130 cso30:c:InputProcess connector
p54_propro_p54
c131 cso30:c:InputProcess connector
p55_propro_p55
c132 cso30:c:InputProcess connector
p56_propro_p56
c134 cso30:c:InputProcess connector
p57_propro_p57
c133 cso30:c:InputProcess connector
p58_propro_p58
c135 cso30:c:InputProcess connector
p59_propro_p59
c136 cso30:c:InputProcess connector
p60_propro_p60
c137 cso30:c:InputProcess connector
p61_propro_p61
c138 cso30:c:InputProcess connector
p62_propro_p62
c139 cso30:c:InputProcess connector
p63_propro_p63
c140 cso30:c:InputProcess connector
p64_propro_p64
c141 cso30:c:InputProcess connector
p65_propro_p65
c163 cso30:c:InputProcess connector
p66_propro_p66
c165 cso30:c:InputProcess connector
p67_propro_p67
c119 cso30:c:InputProcess connector
p68_propro_p68
c120 cso30:c:InputProcess connector
p69_propro_p69
c174 cso30:c:InputProcess connector
p70_propro_p70
c164 cso30:c:InputProcess connector
p71_propro_p71
c162 cso30:c:InputProcess connector
p72_propro_p72
c168 cso30:c:InputProcess connector
p73_propro_p73
c173 cso30:c:InputProcess connector
p74_propro_p74
c166 cso30:c:InputProcess connector
p75_propro_p75
c167 cso30:c:InputProcess connector
p76_propro_p76
c172 cso30:c:InputProcess connector
p77_propro_p77
c169 cso30:c:InputProcess connector
p78_propro_p78
c171 cso30:c:InputProcess connector
p79_propro_p79
c170 cso30:c:InputProcess connector
p80_propro_p80
c159 cso30:c:InputProcess connector
p81_propro_p81
c161 cso30:c:InputProcess connector
p82_propro_p82
c154 cso30:c:InputProcess connector
p83_propro_p83
c153 cso30:c:InputProcess connector
p84_propro_p84
c151 cso30:c:InputProcess connector
p85_propro_p85
c152 cso30:c:InputProcess connector
p86_propro_p86
c150 cso30:c:InputProcess connector
p87_propro_p87
c156 cso30:c:InputProcess connector
p88_propro_p88
c160 cso30:c:InputProcess connector
p89_propro_p89
c157 cso30:c:InputProcess connector
p90_propro_p90
c158 cso30:c:InputProcess connector
p91_propro_p91
c149 cso30:c:InputProcess connector
p92_propro_p92
c148 cso30:c:InputProcess connector
p93_propro_p93
c147 cso30:c:InputProcess connector
p94_propro_p94
c146 cso30:c:InputProcess connector
p95_propro_p95
c142 cso30:c:InputProcess connector
p96_propro_p96
c143 cso30:c:InputProcess connector
p97_propro_p97
c144 cso30:c:InputProcess connector
p98_propro_p98
c145 cso30:c:InputProcess connector
p99_propro_p99
c155 cso30:c:InputProcess connector
p100_propro_p100
c176 cso30:c:OutputProcess connector
p101_propro_p101
c177 cso30:c:OutputProcess connector
p102_propro_p102
c175 cso30:c:OutputProcess connector
p103_propro_p103
c178 cso30:c:OutputProcess connector
p104_propro_p104
c179 cso30:c:OutputProcess connector
p105_propro_p105
c197 cso30:c:OutputProcess connector
p106_propro_p106
c180 cso30:c:OutputProcess connector
p107_propro_p107
c198 cso30:c:OutputProcess connector
p109_propro_p109
c181 cso30:c:OutputProcess connector
p110_propro_p110
c182 cso30:c:OutputProcess connector
p111_propro_p111
c183 cso30:c:OutputProcess connector
p112_propro_p112
c184 cso30:c:OutputProcess connector
p113_propro_p113
c186 cso30:c:OutputProcess connector
p114_propro_p114
c187 cso30:c:OutputProcess connector
p115_propro_p115
c185 cso30:c:OutputProcess connector
p116_propro_p116
c191 cso30:c:OutputProcess connector
p117_propro_p117
c189 cso30:c:OutputProcess connector
p118_propro_p118
c190 cso30:c:OutputProcess connector
p119_propro_p119
c188 cso30:c:OutputProcess connector
p120_propro_p120
p121_propro_p121
c194 cso30:c:OutputProcess connector
p122_propro_p122
c193 cso30:c:OutputProcess connector
p123_propro_p123
c192 cso30:c:OutputProcess connector
p124_propro_p124
c196 cso30:c:OutputProcess connector
p108_propro_p108
p108
c195 cso30:c:OutputProcess connector
IFNalpha_enti_e5
IFNalpha
IFNAR_enti_e6
IFNAR
IFNA:IFNAR_enti_e10
IFNA:IFNAR
IL-1_enti_MO000000214
IL-1
IL-8_enti_MO000017264
IL-8
TNF-alpha_enti_MO000000289
TNF-alpha
TNF-alpha_enti_G010329
TNF-alpha
Il-8_enti_e11
Il-8
Il-1_enti_e12
Il-1
SOCS3_enti_G011948
SOCS3
SOCS1_enti_G010539
SOCS1
TNF-alphaR_enti_e13
TNF-alphaR
TNF-alpha:recpetor_enti_e14
TNF-alpha:recpetor
shp2_enti_e15
shp2
PKR_enti_MO000008179
PKR
NS5A_enti_e16
NS5A
NS5A:PKR_enti_e17
NS5A:PKR
JAKs_enti_e18
JAKs
IFNA:IFNAR:JAK_enti_e19
IFNA:IFNAR:JAK
STAT_enti_e20
STAT
STAT{p}_enti_e21
STAT{p}
STAT{p}_enti_e22
STAT{p}
ISGs_enti_e23
ISGs
DNA:STAT{p}_enti_e24
DNA:STAT{p}
mRNA_enti_e25
mRNA
IFN-beta_enti_G010228
IFN-beta
IFN-alpha_enti_e26
IFN-alpha
HCV E2_enti_e27
HCV E2
HCV E2:PKR {inactive}_enti_e28
HCV E2:PKR {inactive}
SOCS3_enti_e29
SOCS3
IFNAR:JAK:SOCS3_enti_e30
IFNAR:JAK:SOCS3
SHP2_enti_e31
SHP2
IFNAR:JAK:SHP2_enti_e32
IFNAR:JAK:SHP2
IRF-3_enti_MO000007694
IRF-3
ISG15_enti_e33
ISG15
IRF-3:ISG15_enti_e34
IRF-3:ISG15
CBP_enti_MO000099682
CBP
IRF-3:CBP_enti_e35
IRF-3:CBP
p300_enti_e36
p300
IRF-3:p300_enti_e37
IRF-3:p300
SOCS1_enti_e38
SOCS1
IFNAR:JAK:SOCS1_enti_e39
IFNAR:JAK:SOCS1
HCV core_enti_e40
HCV core
LPS_enti_MO000016882
LPS
TLR4_enti_MO000019394
TLR4
LPS:TLR4_enti_e41
LPS:TLR4
CpG DNA_enti_e42
CpG DNA
TLR9_enti_MO000042012
TLR9
CpGDNA:TLR9_enti_e43
CpGDNA:TLR9
IL-6_enti_MO000007384
IL-6
IL-6R_enti_MO000018458
IL-6R
IL-6:IL-6R_enti_e44
IL-6:IL-6R
Il-6:IL-6R:JAKs_enti_e45
Il-6:IL-6R:JAKs
IL-10_enti_MO000017247
IL-10
IL-10R_enti_MO000017252
IL-10R
IL-10:IL-10R_enti_e46
IL-10:IL-10R
Il-10:IL-10R:JAKs_enti_e47
Il-10:IL-10R:JAKs
IRF-3_enti_e48
IRF-3