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

Bax(b)

Bax b

Caspase(csp~Act)

Caspase csp Act

p53(dna!+)

p53 dna

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

PARP DNA CD act 4NAD Inh 4isub

Reaction Rules

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

p53 1 ⬆⬇dna DNADSB 1 ⬆⬇br
PARP binds DNADSB per function

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

PARP 2 ⬆⬇DNA CD inact act take all branches, once each, in any order⬇⬇ NAD DNADSB 2 ⬆⬇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 2DNA CD act 3 ⬆⬇NAD DNADSB 2br NAD 3 ⬆⬇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 2DNA CD act 3 ⬆NAD DNADSB 2br NAD 3 ⬆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 4 ⬆⬇isub PARP 2 ⬆⬇DNA CD act 4 ⬆⬇NAD DNADSB 2 ⬆⬇br
Baseline transcription and degradation of BAX mRNAp53 regulated BAX transcription via Hill function, typical rule for transcriptionBax translation, protein degradationBax--BclXL binding, unbinding

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

Bax 1 ⬆⬇b BclXL 1 ⬆⬇b
Bax (complexed) degradationBclXL and dep'ylated Bad binding, unbinding

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

BclXL 2 ⬆⬇b Bad S75_S99 0 2 ⬆⬇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 3 ⬆⬇b Fourteen_3_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 2 ⬆b Bad S75_S99 0 PP take all branches, once each, in any order⬇⬇ 2 ⬆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⬆⬆ 3 ⬆b Fourteen_3_3 3 ⬆b
Procaspase synthesisCaspase and procaspase degradationCaspase 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⬇⬇