Molecules

DNADSB(br)

DNADSB br

p53(dna)

p53 dna

mRNA_Bax()

mRNA_Bax

Bax(b)

Bax b

BclXL(b)

BclXL b

Bad(S75_S99~0~PP,b)

Bad S75_S99 0 PP b

Fourteen_3_3(b)

Fourteen_3_3 b

Caspase(csp~Pro~Act)

Caspase csp Pro Act

PARP(DNA,CD~inact~act,NAD)

PARP DNA CD inact act NAD

NAD(sub)

NAD sub

XRCC1(Glu~uPAR~PAR)

XRCC1 Glu uPAR PAR

PARG(CD)

PARG CD

Inh(isub)

Inh isub

Species

DNADSB(br)

DNADSB br

p53(dna)

p53 dna

BclXL(b)

BclXL b

Bad(S75_S99~0,b)

Bad S75_S99 0 b

Fourteen_3_3(b)

Fourteen_3_3 b

PARP(DNA,CD~inact,NAD)

PARP DNA CD inact NAD

XRCC1(Glu~uPAR)

XRCC1 Glu uPAR

PARG(CD)

PARG CD

Inh(isub)

Inh isub

Observables

mRNA_Bax mRNA_Bax()

mRNA_Bax

Bax_free Bax(b)

Bax b

Caspase_act Caspase(csp~Act)

Caspase csp Act

p53_DNAbound p53(dna!+)

p53 dna

PARP_Inhbound PARP(DNA,CD~act,NAD!4).Inh(isub!4)

PARP DNA CD act NAD Inh isub

Reaction Rules

p53(dna) + DNADSB(br) <-> p53(dna!1).DNADSB(br!1)

p53 ⬇⬆dna ⬇⬆ DNADSB ⬇⬆br

PARP binds DNADSB per function

PARP(DNA,CD~inact,NAD) + DNADSB(br) <-> PARP(DNA!2,CD~act,NAD).DNADSB(br!2)

PARP ⬇⬆DNA CD inact act take all branches, once each, in any order⬇⬆ NAD ⬇⬆ DNADSB ⬇⬆br

PARP binds substrate NAD

PARP(DNA!2,CD~act,NAD).DNADSB(br!2) + NAD(sub) <-> PARP(DNA!2,CD~act,NAD!3).DNADSB(br!2).NAD(sub!3)

PARP DNA CD act ⬇⬆NAD DNADSB br ⬇⬆ NAD ⬇⬆sub

PARP PARylates XRCC1 as a representative substrate

PARP(DNA!2,CD~act,NAD!3).DNADSB(br!2).NAD(sub!3) + XRCC1(Glu~uPAR) -> PARP(DNA!2,CD~act,NAD).DNADSB(br!2) + NAD(sub) + XRCC1(Glu~PAR)

PARP DNA CD act ⬆NAD DNADSB br ⬆ NAD ⬆sub XRCC1 Glu uPAR PAR take all branches, once each, in any order⬇

PARG de-PARylates XRCC1

PARG(CD) + XRCC1(Glu~PAR) -> PARG(CD) + XRCC1(Glu~uPAR)

PARG CD XRCC1 Glu uPAR PAR take one or more branches, once each, in any order⬆

Inhibitor binds to NAD pocket and PARP falls off DNA.

Inh(isub) + PARP(DNA!2,CD~act,NAD).DNADSB(br!2) <-> Inh(isub!4).PARP(DNA,CD~act,NAD!4) + DNADSB(br)

Inh ⬇⬆isub ⬇⬆ PARP ⬆⬇DNA CD act ⬇⬆NAD ⬆⬇ DNADSB ⬆⬇br

Baseline transcription and degradation of BAX mRNA

0 <-> mRNA_Bax()

mRNA_Bax synthesized

p53 regulated BAX transcription via Hill function, typical rule for transcription

0 -> mRNA_Bax()

mRNA_Bax synthesized

Bax translation, protein degradation

0 <-> Bax(b)

Bax b synthesized

Bax--BclXL binding, unbinding

Bax(b) + BclXL(b) <-> Bax(b!1).BclXL(b!1)

Bax ⬇⬆b ⬇⬆ BclXL ⬇⬆b

Bax (complexed) degradation

Bax(b!1).BclXL(b!1) -> BclXL(b)

Bax ⬆b degraded ⬆ BclXL ⬆b

BclXL and dep'ylated Bad binding, unbinding

BclXL(b) + Bad(S75_S99~0,b) <-> BclXL(b!2).Bad(S75_S99~0,b!2)

BclXL ⬇⬆b ⬇⬆ Bad S75_S99 0 ⬇⬆b

Bad p'ylation by AKT, dep'ylation

Bad(S75_S99~0,b) <-> Bad(S75_S99~PP,b)

Bad S75_S99 0 PP take all branches, once each, in any order⬇⬆ b

Bad (p'ylated) and 14-3-3 binding, unbinding

Bad(S75_S99~PP,b) + Fourteen_3_3(b) <-> Bad(S75_S99~PP,b!3).Fourteen_3_3(b!3)

Bad S75_S99 PP ⬇⬆b ⬇⬆ Fourteen_3_3 ⬇⬆b

BclXL unbinding from Bad upon Bad p'ylation by AKT.

BclXL(b!2).Bad(S75_S99~0,b!2) -> BclXL(b) + Bad(S75_S99~PP,b)

BclXL ⬆b ⬆ Bad S75_S99 0 PP take all branches, once each, in any order⬇ ⬆b

Unbinding of Bad from 14-3-3 upon Bad dep'ylation

Bad(S75_S99~PP,b!3).Fourteen_3_3(b!3) -> Bad(S75_S99~0,b) + Fourteen_3_3(b)

Bad S75_S99 0 PP take one or more branches, once each, in any order⬆ ⬆b ⬆ Fourteen_3_3 ⬆b

Procaspase synthesis

0 -> Caspase(csp~Pro)

Caspase csp Pro synthesized

Caspase and procaspase degradation

Caspase() -> 0

Caspase csp Pro ?Act degraded

Caspase activation by Bax and by other caspases

Caspase(csp~Pro) -> Caspase(csp~Act)

Caspase csp Pro Act take all branches, once each, in any order⬇