Additional le 2: Model parameters and their justication

Symbol Values Units Description Comments W0 2 10 12 l cell volume Assumed [1] kv = V=U 5 cytoplasmic to nuclear volume Assumed kb 4 10 6 s 1ml=ng receptor activation rate Assumed kf 6 10 4 s 1 receptor inactivation rate Fitted [3] q1 1:5 10 7 s 1 NFB driven activation of I B and A20 genes Fitted q2 10 6 s 1 I B mediated NFB dissociation from I B and A20 sites Assumed KN 104 total number of IKKK molecules Assumed KNN 2 105 total number of IKK molecules Assumed M 103 total number of receptors Assumed NFBtot 105 total number of NFB molecules Assumed [1] ka 10 4 s 1 IKKK activation rate Assumed ki 0:01 s 1 IKKK inactivation rate Assumed c1 0:1 s 1 inducible A20 and I B mRNA synthesis Assumed c3 0:00075 s 1 A20 and I B mRNA degradation Fitted [2] c4 0:5 s 1 A20 and I B translation rate Fitted c5 0:0005 s 1 A20 degradation rate Fitted ka20 104 A20 TNFR1 block Fitted k2 104 IKKa inactivation due to A20 Fitted k1 5 10 6 s 1 IKKn activation rate Fitted k3 0:003 s 1 IKKa inactivation rate Fitted k4 0:0005 s 1 IKKii transformation Fitted a1 5 10 7 s 1 I B –NF B association Assumed [4] a2 10 7 s 1 IKKa mediated I B phosphorylation Fitted a3 5 10 7 s 1 IKKa mediated ( NF BjI B ) phosphorylation Fitted tp 0:01 s 1 degradation of P-I B and P-I B bounded to NFB Fitted c5a 0:0001 s 1 degradation of I B Assumed [5] c6a 0:00002 s 1 spontaneous degradation of I B bounded to NFB Assumed [5] i1 0:01 s 1 NFB nuclear import Fitted e2a 0:05 s 1 I B jNFB nuclear export Fitted i1a 0:002 s 1 I B nuclear import Fitted e1a 0:005 s 1 I B nuclear export Fitted