From: Explaining oscillations and variability in the p53-Mdm2 system
Reac No.a | Name | Term | Kinetic law | Parameter valuesb | Â |
---|---|---|---|---|---|
1 | p53 synthesis | GO:0006412 | k synp 53 | 7.8E-2 mol s-1 | Based on p53 half-life ~20 min [12]. |
2 | p53/Mdm2 binding | GO:0002039 | kbinMdm 2p 53<#p53><#Mdm2> | 1.155E-3 mol-1 s-1 | Assumed that 95% of p53 is bound to Mdm2 under normal conditions. |
3 | Mdm2_p53 dissociation | GO:0043624 | krelMdm 2p 53<#Mdm2_p53> | 1.155E-5 s-1 | Based on dissociation constant of ~100 molecules [56]. |
4 | p53 degradation | GO:0043161 | kdegp 53<#Mdm2_p53> | 8.25E-4 s-1 | p53 half-life ~20 min [12]. |
5 | Mdm2 Transcription | GO:0003700 | ksynMdm 2mRNA<#p53> | 1.0E-4 s-1 | Turnover of Mdm2_mRNA was adjusted to give period of oscillations ~5–6 h [35]. |
6 | Mdm2_mRNA degradation | GO:0006402 | kdegMdm 2mRNA<#Mdm2_mRNA> | 1.0E-4 s-1 | Â |
7 | Mdm2 synthesis | GO:0006412 | ksynMdm 2<#Mdm2_mRNA> | 4.95E-4 s-1 | Based on Mdm2 half-life ~30 min [12]. |
8 | Mdm2 degradation | GO:0043161 | kdegMdm 2<#Mdm2> | 4.33E-4 s-1 | Mdm2 half-life ~30 min [12]. |
9 | DNA damage | GO:0006974 | k dam <#IR> | 8.0E-2 s-1 | Based on about 30 double strand breaks per cell per Gy irradiation [64]. |
10 | DNA repair | GO:0006281 | k repair <#damDNA> | 2.0E-5 s-1 | This was set so that all DNA damage was repaired by ~10–16 h[65]. |
11 | ARF activation | GO:0030330 | k actARF <#damDNA> | 3.3E-5 s-1 | ARF is activated within 1 hour of DNA damage and activity peaks at 6 h. |
12 | ARF/Mdm2 binding | GO:0005515 | kbinARFMdm 2<#ARF><#Mdm2> | 1.0E-2 mol-1 s-1 | This was set so that ARF/Mdm2 complexes peaks at 6–8 h after IR [23]. |
13 | ARF degradation | GO:0043161 | k degARF <#ARF> | 1.0E-4 s-1 | Based on ARF half-life ~6 h [66]. |
14 | ARF-dependent Mdm2 degradation | GO:0043161 | kdegARFMdm 2<# ARF_Mdm2> | 1.0E-3 s-1 | Assumed to be 3-fold faster than normal degradation 7[25]. |