From: A systems biology approach to suppress TNF-induced proinflammatory gene expressions
Reaction | Formula and parameters (s^{-1}) | Remarks | ||||||||
---|---|---|---|---|---|---|---|---|---|---|
1 ^{1} | TNFR1 | → | TRADD | k _{ 1 } | * | TNFR1 | k _{ 1 } | = | 5e-3 | Activation of TRADD by TNFR1 |
2 ^{2} | TRADD | → | cIAP1/2 | k _{ 2 } | * | TRADD | k _{ 2 } | = | 2e-2 | Formation of Complex 1 containing TRADD, cIAP1/2, TRAF2, TRAF5, RIP1 and the TAB/TAK complex |
3 ^{3} | cIAP1/2 | → | TRAF2 | k _{ 3 } | * | cIAP1/2 | k _{ 3 } | = | 1e-2 | |
4 ^{4} | cIAP1/2 | → | TRAF5 | k _{ 4 } | * | cIAP1/2 | k _{ 4 } | = | 8e-3 | |
5 ^{5} | TRAF2 | → | RIP1 | k _{ 5 } | * | TRAF2 | k _{ 5 } | = | 1e-3 | |
6 ^{5} | TRAF5 | → | RIP1 | k _{ 6 } | * | TRAF5 | k _{ 6 } | = | 1e-3 | |
7 ^{6} | TRADD | → | TRAF6 | k _{ 7 } | * | TRADD | k _{ 7 } | = | 2e-2 | Activation of TRAF6 by TRADD |
8 ^{5} | TRAF6 | → | RIP1 | k _{ 8 } | * | TRAF6 | k _{ 8 } | = | 1e-4 | Activation of RIP1 and TAK1 complex by TRAF6 |
9 ^{7} | TRAF6 | → | TAK1 complex | k _{ 9 } | * | TRAF6 | k _{ 9 } | = | 1.3e-4 | |
10 ^{8} | RIP1 | → | LUBAC | k _{ 10 } | * | RIP1 | k _{ 10 } | = | 7e-3 | Complex 1 ubiquitination by LUBAC and SHARPIN |
11 ^{9} | RIP1 | → | SHARPIN | k _{ 11 } | * | RIP1 | k _{ 11 } | = | 7e-3 | |
12 ^{7} | LUBAC | → | TAK1 complex | k _{ 12 } | * | LUBAC | k _{ 12 } | = | 1e-1 | |
13 | SHARPIN | → | IKK complex | k _{ 13 } | * | SHARPIN | k _{ 13 } | = | 1e-2 | Activation of IKK complex by Complex 1 |
14 | TAK1 complex | → | IKK complex | k _{ 14 } | * | TAK1 complex | k _{ 14 } | = | 1e-1 | |
15 ^{10} | IKK complex | → | IκBα | k _{ 15 } | * | IKK complex | k _{ 15 } | = | 1e-2 | Phosphorylation of IκBα by IKK |
16 | IκBα | → | NF-κBc | k _{ 16 } | * | IκBα | k _{ 16 } | = | 8e-3 | Degradation of IκBα forms NF-κB |
17 | NF-κBc | → | NF-κBn | k _{ 17 } | * | NF-κBc | k _{ 17 } | = | 1.7e-2 | Translocation of NF-κB to nucleus |
18 | TAK1 complex | → | MKK1/2 | k _{ 18 } | * | TAK1 complex | k _{ 18 } | = | 1.5e-3 | Activation of MAP kinases kinases by TAK1 complex |
19 ^{11} | TAK1 complex | → | MKK3/6 | k _{ 19 } | * | TAK1 complex | k _{ 19 } | = | 1e-2 | |
20 | TAK1 complex | → | MKK4/7 | k _{ 20 } | * | TAK1 complex | k _{ 20 } | = | 1e-2 | |
21 | MKK1/2 | → | ERK | k _{ 21 } | * | MKK1/2 | k _{ 21 } | = | 5e-3 | Activation of MAP kinases |
22 ^{12} | MKK3/6 | → | p38 | k _{ 22 } | * | MKK3/6 | k _{ 22 } | = | 5e-3 | |
24 | MKK4/7 | → | JNK | k _{ 23 } | * | MKK4/7 | k _{ 23 } | = | 5e-3 | |
24 | p38 | → | p38n | k _{ 24 } | * | p38 | k _{ 24 } | = | 5e-2 | Translocation of MAP kinases into nucleus |
25 | JNK | → | JNKn | k _{ 25 } | * | JNK | k _{ 25 } | = | 5e-2 | |
26 | ERK | → | ERKn | k _{ 26 } | * | ERK | k _{ 26 } | = | 5e-3 | |
27 | p38n | → | AP1 | k _{ 27 } | * | p38n | k _{ 27 } | = | 1e-2 | Activation of AP1 by MAP kinases |
28 | ERKn | → | AP1 | k _{ 28 } | * | ERKn | k _{ 28 } | = | 1e-2 | |
29 | JNKn | → | AP1 | k _{ 29 } | * | JNKn | k _{ 29 } | = | 1e-2 | |
30 | AP1 | → | GI promoter | k _{ 30 } | * | AP1 | k _{ 30 } | = | 1e-1 | Promoter binding of AP1 and NF-κB for group I genes |
31 | NF-κBn | → | GI promoter | k _{ 31 } | * | NF-κBn | k _{ 31 } | = | 5e-3 | |
32 | G1 promoter | → | GI pre-mRNA | k _{ 32 } | * | GI promoter | k _{ 32 } | = | 1e-2 | Group I genes transcription, splicing (1 step) and decay |
33 | GI pre-mRNA | → | GI mRNA | k _{ 33 } | * | GI pre-mRNA | k _{ 33 } | = | 5e-2 | |
34 | GI mRNA | → | GI mRNA decay | k _{ 34 } | * | GI mRNA | k _{ 34 } | = | 2e-3 | |
35 ^{13} | AP1 | → | GII promoter | k _{ 35 } | * | AP1 | k _{ 35 } | = | 1.1e-2 | Promoter binding of AP1 and NF-κB for group II genes |
36 | NF-κBn | → | GII promoter | k _{ 36 } | * | NF-κBn | k _{ 36 } | = | 4e-3 | |
37 | GII promoter | → | GII pre-mRNA/1 | k _{ 37 } | * | GII promoter | k _{ 37 } | = | 2e-3 | Group II genes transcription, splicing (2 steps) and decay |
38 | GII pre-mRNA/1 | → | GII pre-mRNA/2 | k _{ 38 } | * | GII pre-mRNA/1 | k _{ 38 } | = | 5e-2 | |
39 | GII pre-mRNA/2 | → | GII mRNA | k _{ 39 } | * | GII pre-mRNA/2 | k _{ 39 } | = | 5e-2 | |
40 ^{13} | GII mRNA | → | GII mRNA decay | k _{ 40 } | * | GII mRNA | k _{ 40 } | = | 1.2e-4 | |
41 | AP1 | → | GIII promoter | k _{ 41 } | * | AP1 | k _{ 41 } | = | 5e-3 | Promoter binding of AP1 and NF-κB for group III genes |
42 | NF-κBn | → | GIII promoter | k _{ 42 } | * | NF-κBn | k _{ 42 } | = | 1e-4 | |
43 | GIII promoter | → | GIII pre-mRNA/1 | k _{ 43 } | * | GIII promoter | k _{ 43 } | = | 1e-1 | Group III genes transcription, splicing (3 steps) and decay |
44 | GIII pre-mRNA/1 | → | GIII pre-mRNA/2 | k _{ 44 } | * | GIII pre-mRNA/1 | k _{ 44 } | = | 4e-4 | |
45 | GIII pre-mRNA/2 | → | GIII pre-mRNA/3 | k _{ 45 } | * | GIII pre-mRNA/2 | k _{ 45 } | = | 1e-3 | |
46 | GIII pre-mRNA/3 | → | GIII mRNA | k _{ 46 } | * | GIII pre-mRNA/3 | k _{ 46 } | = | 2e-4 | |
47 | GIII mRNA | → | GIII mRNA decay | k _{ 47 } | * | GIII mRNA | k _{ 47 } | = | 2e-5 | |
48 | GI mRNA | → | X1 | k _{ 48 } | * | GI mRNA | k _{ 48 } | = | 1e-5 | Feedback processes via group I genes or NF-κB |
49 | NF-κBn | → | X1 | k _{ 49 } | * | NF-κBn | k _{ 49 } | = | 5e-1 | Steps of the secondary feedback processes (cytosolic or autocrine signaling): |
50 | X1 | → | X2 | k _{ 50 } | * | X1 | k _{ 50 } | = | 2e-3 | |
51 | X2 | → | X3 | k _{ 51 } | * | X2 | k _{ 51 } | = | 2e-3 | |
52 | X3 | → | X4 | k _{ 52 } | * | X3 | k _{ 52 } | = | 2e-3 | |
53 | X4 | → | X5 | k _{ 53 } | * | X4 | k _{ 53 } | = | 2e-3 | |
54 | X5 | → | X6 | k _{ 54 } | * | X5 | k _{ 54 } | = | 2e-3 | |
55 | X6 | → | X7 | k _{ 55 } | * | X6 | k _{ 55 } | = | 2e-3 | • expression (e.g. translation) |
56 | X7 | → | X8 | k _{ 56 } | * | X7 | k _{ 56 } | = | 2e-3 | • transport (e.g. secretion) |
57 | X8 | → | X9 | k _{ 57 } | * | X8 | k _{ 57 } | = | 2e-3 | • signaling (e.g. receptor binding, activation of transcription factors) |
58 | X9 | → | X10 | k _{ 58 } | * | X9 | k _{ 58 } | = | 2e-3 | |
59 | X10 | → | X11 | k _{ 59 } | * | X10 | k _{ 59 } | = | 2e-3 | |
60 | X11 | → | X12 | k _{ 60 } | * | X11 | k _{ 60 } | = | 2e-3 | |
61 | X12 | → | X13 | k _{ 61 } | * | X12 | k _{ 61 } | = | 2e-3 | |
62 | X13 | → | X14 | k _{ 62 } | * | X13 | k _{ 62 } | = | 2e-3 | |
63 | X14 | → | IκBα | k _{ 63 } | * | X14 | k _{ 63 } | = | 2e-3 | IκBα feedback activation |
64 | X14 | → | Y | k _{ 64 } | * | X14 | k _{ 64 } | = | 1e-5 | Group III feedback activation via transcription factor Y |
65 | Y | → | GIII promoter | k _{ 65 } | * | Y | k _{ 65 } | = | 2e-3 |