Table 3.
FOXO parameters for synthesis, degradation, transport and PTMs
| Process | 2o rate constant (#min-1) | Enzyme | Enz # | 1o rate const (min-1) | PTM modifying rate | Rate MF | Reference |
|---|---|---|---|---|---|---|---|
| Synthesis (NULL → FOXO) |
0.0055 |
E2F1 |
300 |
5.5 |
|
|
[45] Figure 1 |
| Cytoplasm → nuclear transport |
- |
- |
- |
0.1/0.55 = 0.182 |
|
|
[3], [46] |
| |
|
|
|
|
Akt-Phos Pa |
0.1 |
[46] |
| |
|
|
|
|
IKK-Phos Pd |
0.5 |
[47] Figure 1 |
| |
|
|
|
|
JNK-Phos Pe |
10 |
[44] |
| Nuclear → cytoplasm transport |
- |
- |
- |
0.1 × 0.55 = 0.055 |
|
|
[3], [46] |
| |
|
|
|
|
Akt-Phos Pa |
10 |
[46] |
| |
|
|
|
|
IKK-phos Pd |
10 |
[47] |
| |
|
|
|
|
JNK-Phos Pe |
0.1 |
[44] |
| Nuclear → DNAbound transport |
- |
- |
- |
0.25 |
|
|
[48] |
| |
|
|
|
|
Akt-Phos Pa |
0.5 |
[49] Figure 6B |
| DNAbound → Nuclear transport |
- |
- |
- |
0.25 × 0.5 = 0.125 |
|
|
[48] |
| basal phosphorylation |
5 × 10-5 |
|
|
|
|
|
|
| basal dephosphorylation |
1 × 10-6 |
|
|
|
|
|
|
| akt_phos_ factor |
6 |
|
|
|
|
|
|
| ikk phos_factor |
3 |
|
|
|
|
|
|
| jnk phos_factor |
2 |
|
|
|
|
|
|
| FOXO → FOXO_Pa |
akt phos_factor × basal phosphorylation |
Akt |
(104) |
0.5 |
|
|
[50] Figure 1C |
| FOXO_Pa → FOXO |
basal dephosphorylation |
PP2A |
5 × 105 |
0.5 |
|
|
|
| FOXO → FOXO_Pd |
ikk phos_factor × basal phosphorylation |
IKK |
(104) |
0.5 |
|
|
[47] |
| FOXO_Pd → FOXO |
basal dephosphorylation |
PP2A |
5 × 105 |
0.5 |
|
|
|
| FOXO → FOXO_Pe |
jnk phos_factor × basal phosphorylation |
JNK |
(104) |
0.5 |
|
|
[44] |
| FOXO_Pe → FOXO |
basal dephosphorylation |
PP2A |
5 × 105 |
0.5 |
|
|
|
| FOXO → FOXO_pUb |
1 × 10-6 |
SCF/MDM2 |
103 |
10-3 |
|
|
[45] Figure 1; also [51] |
| |
|
|
|
|
Akt (Pa) |
3 |
[45] Figure 1 |
| |
|
|
|
|
IKK (Pd) |
22 |
[47] Figure 5F |
| Degradation (FOXO_pUb → NULL) | 1 × 10-4 | Proteasome | 103 | 0.1 | [45] Figure 1 |
Kinetic parameters of the FOXO module of the model. Where a second-order rate constant is given and the Enzyme is time-varying, the Enz # and first order rate constant columns show typical values when the process is activated. The PTM modifying rate refers to the way modifiable species are implemented in this system: if the PTM is present, then the basal rate for the process (in the 1o rate column) is multiplied by the entry in the Rate MF (Multiplicative Factor) column.