From: Modelling the onset of senescence at the G1/S cell cycle checkpoint
Node | Rule / level interpretation | |
---|---|---|
ATM | 1: DSB = 1 | Low level of DSB signal |
 | 2: DSB = 2 | High level of DSB signal |
ATR | 1: SSB = 1 | Low level of SSB signal |
 | 2: SSB = 2 | High level of SSB signal |
CHEK2 | 1: ATM = 2 | |
CHEK1 | 1: ATR = 2 OR ATM = 2 | |
p14ARF | 1: p38MAPK = 2 OR E2F | |
p38MAPK | 1: (ATM = 1 OR ATR = 1-2) AND NOT(ATM = 2) | Activated p38MAPK pathway (leading to cycle arrest) |
 | 2: ATM = 2 AND NOT(ATR = 2) | Middle level of p38MAPK pathway activation (leading to senescence) |
 | 3: ATM = 2 AND ATR = 2 | Highest level of p38MAPK pathway activation (leading to apoptosis) |
Mdm2 | 1: p53 = 1 AND NOT(p14ARF) | |
p16INK4A | 1: p38MAPK = 1-2 | Activated p16INK4A |
 | 2: p38MAPK = 3 | p16 INK4A upregulation |
p21 | 1: p53 = 1 | |
p53 | 1: Mdm2 = 1 AND (p38MAPK = 3 OR ATR = 1-2 OR ATM = 1-2 OR CHEK1 = 1 OR CHEK2 = 1) | Activated p53 (no accumulation) |
 | 2: NOT(Mdm2 = 1) AND (p38MAPK = 3 OR ATR = 1-2 OR ATM = 1-2 OR CHEK1 = 1 OR CHEK2 = 1) | p53 accumulation leading to apoptosis |
CDC25A | 1: (p38MAPK = 1-3 OR CHEK2 = 1 OR CHEK1 = 1) AND NOT(p38MAPK = 1-3 AND CHEK2 = 1 AND CHEK1 = 1) | Low concentration of active Cdc25A (i.e. non-phosphorylated) |
 | 2: NOT(p38MAPK = 1-3) AND NOT(CHEK2 = 1) AND NOT(CHEK1 = 1) | High concentration of active Cdc25A |
E2F | 1: NOT(RB1 = 1) | |
RB1 | 1: NOT(CDK46CycDc = 1) AND NOT(CDK2CycEc =1) | Dephosphorylated RB1 bound to E2F |
CDK46CycD | 1: Cdc25A = 1 AND NOT(p16INK4a = 1-2) AND NOT(p21 = 1) | |
CDK2CycE | 1: NOT(p21 = 1) AND Cdc25A = 2 AND E2F = 1 | |
apoptosis | 1: p53 = 2 | |
proliferation | 1: CDK2CycEc = 1 | |
senescence | 1: (p16INK4a = 1 AND p21 = 1 AND NOT(Cdc25A = 1-2) AND NOT(p53 = 2)) OR (p16INK4a = 2 AND p21 = 1 AND NOT(Cdc25A = 2) AND NOT(p53 = 2)) | |
cyclearrest | 1: NOT(CDK2CycEc = 1) |