Skip to main content

Table 3 Reactions involved in p53 turnover and the DNA damage response

From: GSK3 and p53 - is there a link in Alzheimer's disease?

No. Name Reactants and products Kinetic lawa Parameter values
25 p53 synthesis p53_mRNA→p53+p53_mRNA ksynp53 <#p53_mRNA> 7.0E-3 s-1
26 p53 Mdm2 binding p53+Mdm2 → Mdm2_p53 kbinMdm2p53<#p53><#Mdm2> 3.0E-3 molecule-1 s-1
27 Mdm2_p53 release Mdm2_p53→p53+Mdm2 krelMdm2p53 <#Mdm2_p53> 3.0E-5 s-1
  E1/Ub binding E1+Ub+ATP→E1_Ub+AMP kbinE1Ub<#E1><#Ub><#ATP>/(5000 +<#ATP>) 2.0E-4 molecule-1 s-1
  E2/Ub binding E1_Ub+E2→E2_Ub+E1 kbinE2Ub<#E2><#E1_Ub> 1.0E-3 molecule-1 s-1
28 p53 ubiquitination Mdm2_p53+E2_Ub→Mdm2_p53_Ub+E2 kp53Ub<#Mdm2_p53><#E2_Ub> 5.0E-5 molecule-1 s-1
29 p53 polyubiquitination1 Mdm2_p53_Ub+E2_Ub→Mdm2_p53_
Ub2+E2
kp53PolyUb<#Mdm2_p53_Ub><#E2_Ub> 1.0E-2 molecule-1 s-1
30 p53 polyubiquitinationX
(X = 2-3)
Mdm2_p53_Ub(X)+E2_Ub→
Mdm2_p53_Ub(X+1)+E2
kp53PolyUb<#Mdm2_p53_Ub(X)><#E2_Ub> 1.0E-2 molecule-1 s-1
  p53 de-ubiquitination1 Mdm2_p53_Ub+p53DUB →
Mdm2_p53+p53DUB+Ub
kactDUBp53<#Mdm2_p53_Ub>
<#p53DUB>
1.0E-7 molecule-1 s-1
  p53 de-ubiquitinationX
(X = 2-4)
Mdm2_p53_Ub(X)+p53DUB →
Mdm2_p53_Ub(X-1)+p53DUB+Ub
kactDUBp53<#Mdm2_p53_Ub(X)>
<#p53DUB>
1.0E-7 molecule-1 s-1
31 p53 Proteasome binding Mdm2_P_p53_Ub4+Proteasome→
p53_Ub4_Proteasome+Mdm2
k binProt <# Mdm2_P_p53_Ub4><#Proteasome> 2.0E-6 molecule-1 s-1
32 p53 degradation p53_Ub4_Proteasome+ATP→
4Ub+Proteasome+ADP
kdegp53<#p53_Ub4_Proteasome> <#ATP>/(5000 + <#ATP>) 1.0E-2 s-1
33 Mdm2mRNA synthesis1 p53→p53+Mdm2_mRNA ksynMdm2mRNA<#p53> 5.0E-4 s-1
(33) Mdm2mRNA synthesis2 p53_P→p53_P+Mdm2_mRNA ksynMdm2mRNA<#p53_P> 5.0E-4 s-1
34 Mdm2 mRNA degradation Mdm2_mRNA→Sink kdegMdm2mRNA<#Mdm2_mRNA> 5.0E-4 s-1
35 Mdm2 synthesis Mdm2_mRNA→Mdm2_mRNA+Mdm2 ksynMdm2<#Mdm2_mRNA> 4.95E-4 s-1
  Mdm2 ubiquitinationb Mdm2+E2_Ub→Mdm2_Ub+E2 kMdm2Ub<#Mdm2><#E2_Ub> 4.56E-6 molecule-1 s-1
  Mdm2 polyubiquitination1c Mdm2_Ub+E2_Ub→Mdm2_Ub2+E2 kMdm2PolyUb<#Mdm2_Ub><#E2_Ub> 4.56E-3 molecule-1 s-1
  Mdm2 polyubiquitinationXc
(X = 2-3)
Mdm2_Ub(X)+E2_Ub→Mdm2_Ub(X+1)+E2 kMdm2PolyUb<#Mdm2_Ub(X)><#E2_Ub> 4.56E-3 molecule-1 s-1
  Mdm2 de-ubiquitination1c Mdm2_Ub+Mdm2DUB →
Mdm2+Mdm2DUB+Ub
kactDUBMdm2<#Mdm2_Ub><#Mdm2DUB> 1.0E-7 molecule-1 s-1
  Mdm2 de-ubiquitinationXc
(X = 2-4)
Mdm2_Ub(X)+Mdm2DUB →
Mdm2_Ub(X-1)+Mdm2DUB+Ub
kactDUBMdm2<#Mdm2_Ub(X)>
<#Mdm2DUB>
1.0E-7 molecule-1 s-1
  Mdm2 proteasome bindingc Mdm2_Ub4 + Proteasome→Mdm2_Ub4_Proteasome k binProt <# Mdm2_Ub4><#Proteasome> 2.0E-6 molecule-1 s-1
  Mdm2 degradationc Mdm2_Ub4_Proteasome+ATP→
4Ub+Proteasome+ADP
kdegMdm2<#Mdm2_Ub4_Proteasome>
<#ATP>/(5000+<#ATP>)
1.0E-2 molecule-1 s-1
36 ATM activation damDNA+ATMI→damDNA+ATMA k actATM <#damDNA><#ATMI> 1.0E-4 molecule-1 s-1
37 ATM inactivation ATMA → ATMI k inactATM <#ATMA> 5.0E-4 s-1
38 p53 phosphorylation p53+ATMA→p53_P+ATMA kphosp53<#p53><#ATMA> 2.0E-4 molecule-1 s-1
39 p53 dephosphorylation p53_P→p53 kdephosp53<#p53_P> 5.0E-1 s-1
  Mdm2 phosphorylation Mdm2+ATMA→Mdm2_P+ATMA kphosMdm2<#Mdm2><#ATMA> 2.0 molecule-1 s-1
  Mdm2 de-phosphorylation Mdm2_P→Mdm2 kdephosMdm2<#Mdm2_P> 5.0E-1 s-1
40 p53mRNA synthesis Source→p53_mRNA k synp53mRNA 1.0E-3 molecule s-1
41 p53mRNA degradation p53_mRNA→Sink kdegp53mRNA<#p53_mRNA> 1.0E-4 s-1
42 DNA damage by IR IR→damDNA+ IR k dam <#IR> 8.0E-2 s-1
43 DNA repair damDNA→Sink k repair <#damDNA> 2.0E-5 s-1
44 DNA damage by ROS ROS→damDNA+ROS k damROS <#ROS> 1.0E-5 s-1
(44) DNA damage by basalROS basalROS→damDNA+ basalROS k dambasalROS <#basalROS> 1.0E-9 s-1
  1. a <#X> means number of molecules of species X, bMdm2_P is also ubiquitinated in the same way but the first step occurs at a higher rate (kMdm2PUb= 6.84E-6). cMdm2_P undergoes polyubiquitination, de-ubiquitination, binding to the proteasome and degradation at the same rate as Mdm2. We assume that the reaction volume is equal to one. Reactions with number in 1st column are shown in Figure 2; reactions with numbers in parentheses are similar to the reactions shown in Figure 2.