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Table 5 List of changed and additional reactions for the ATM 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

ksynp 53<#p53_mRNA>

6.0E-3 s-1

Based on p53 half-life ~20 min[12]

15

ATM activation

GO:0006468

k actATM <#damDNA><#ATMI>

1.0E-4 mol-1 s-1

Phosphorylation takes place on time-scale of a few minutes. Rate of reaction depends on amount of damaged DNA and pool of ATMI.

16

ATM inactivation

GO:0006470

k inactATM <#ATMA>

5.0E-4 s-1

De-phosphorylation is of the same order of magnitude as phosphorylation.

17

p53 phosphorylation

GO:0006468

kphosp 53<#p53><#ATMA>

5.0E-4 mol-1 s-1

Phosphorylation takes place on time-scale of a few minutes.

18

p53 dephosphorylation

GO:0006470

kdephosp 53<#p53_P>

5.0E-1 s-1

This parameter was varied to obtain oscillations.

19

Mdm2 Transcription

GO:0003700

ksynMdm 2mRNA<#p53_P>

1.0E-4 s-1

Same as ARF model

20

Mdm2 phosphorylation

GO:0006468

kphosMdm 2<#Mdm2><#ATMA>

2.0 mol-1 s-1

This is more rapid th.an phosphorylation of p53 by ATM [22].

21

Mdm2 de-phosphorylation

GO:0006470

kdephosMdm 2<#Mdm2_P>

5.0E-1 s-1

De-phosphorylation is of the same order of magnitude as phosphorylation.

22

Mdm2 degradation enhanced by ATM

GO:0043161

kdegMdm 2ATM<#Mdm2_P>

4.0E-4 s-1

Mdm2 is degraded at higher rate after phosphorylation by ATM[21].

23

p53_mRNA synthesis

GO:0009299

k synp 53mRNA

1.0E-3 mol s-1

Assume turnover of mRNA is about 2 hours

24

p53_mRNA degradation

GO:0006402

kdegp 53mRNA<#p53_mRNA>

1.0E-4 s-1

 
  1. aReaction numbers correspond to the numbered arrows in Figures 3 and 9, bmol refers to the number of molecules