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Table 2 List of reactions for the ARF model

From: Explaining oscillations and variability in the p53-Mdm2 system

Reac No.a

Name

Term

Kinetic law

Parameter valuesb

 

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

 

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].

  1. aReaction numbers correspond to the numbered arrows in Figure 3, bmol refers to the number of molecules