From: Modelling the onset of senescence at the G1/S cell cycle checkpoint
Loss-Of-Function (LoF) | ||
---|---|---|
Gene | Model outcome | Experimental outcome |
Comparison with experiments whose protocol include DNA damage | ||
p38MAPK | Loss of senescence and of apoptosis | Reduced apoptosis [35] |
CHEK2 | Loss of senescence | Loss of senescence [37] |
ATM | Loss of senescence and of apoptosis | Reduced apoptosis [41] |
Comparison with experiments whose protocol does not include DNA damage | ||
CHEK1 | No damage: proliferation With damage: loss of senescence | Apoptosis enhanced [42] |
p14ARF | No damage: proliferation With damage: senescence enhanced & loss of apoptosis | ? |
Mdm2 | No damage: proliferation With damage: apoptosis | Apoptosis [45] |
p16INK4a | No damage: proliferation With damage: loss of senescence | Loss of senescence |
p21 | No damage: proliferation With damage: loss of senescence | Proliferation [47] |
p53 | No damage: proliferation With damage: loss of senescence & apoptosis | Proliferation & loss of senescence [48] |
ATR | No damage: proliferation With damage: senescence enhanced & loss of apoptosis | ? |
CDC25A | No damage: loss of proliferation With damage: senescence enhanced | ? |
RB1 | No damage: proliferation With damage: apoptosis | Apoptosis enhanced [50] |
E2F | No damage: loss of proliferation With damage: similar to the wild type | Loss of proliferation [51] |
p53 & Mdm2 | No damage: proliferation With damage: loss of senescence & apoptosis | Proliferation [45] |
Gain-Of-Function (GoF) | ||
Gene | Model outcome | Experimental outcome |
Comparison with experiments whose protocol include DNA damage | ||
CHEK2 | Senescence enhanced | |
Mdm2 | Senescence enhanced & loss of apoptosis | Loss of apoptosis [46] |
p21 | Similar to the wild type | Loss of proliferation or senescence [43] |
Comparison with experiments whose protocol does not include DNA damage | ||
p38MAPK | No damage: [1, 2] loss of proliferation; [3] apoptosis With damage: [1, 2] senescence enhanced & loss of apoptosis; [3] apoptosis | Senescence [36] |
CHEK1 | No damage: loss of proliferation With damage: similar to the wild type | ? |
p14ARF | No damage: proliferation With damage: apoptosis | Apoptosis [43] |
p16INK4a | No damage: cell cycle arrest with probability ~ 0.9 With damage: [1, 2] similar to the wild type; [2] senescence enhanced | |
p53 | No damage: [1, 2] loss of proliferation; [2] apoptosis With damage: [1] senescence enhanced & loss of apoptosis; [2]: apoptosis | |
ATM | No damage: [1] loss of proliferation; [2] senescence With damage: [1] loss of senescence & apoptosis; [2] senescence enhanced | ? |
ATR | No damage: [1, 2] loss of proliferation With damage: [1] senescence enhanced & loss of apoptosis; [2] loss of senescence & apoptosis enhanced | Senescence [32] |
CDC25A | Proliferation [49] | |
RB1 | No damage: loss of proliferation With damage: similar to the wild type | Cycle arrest [48] |
E2F | No damage: proliferation With damage: apoptosis | Apoptosis [51] |