Figure 1.
Rb-E2F pathway mediated by miR449.
Rb-E2F circuit coupling the positive feedback loops and negative feedback loops mediated by miR449. E2F represents all E2F activators (E2F1, E2F2 and E2F3a). Rb represents all pocket proteins (Rb, p130 and p107). MiR449 represents miR449 family (miR449a, miR449b and miR449c).
Table 1.
Parameters values for the mathematical model.
Figure 2.
Bifurcation diagram of [E2F] with as a control parameter at
.
Set the AUTO axes to run from 0 to 1.2 along the x-axis and from −0.05 to 1.25 along the y-axis. The initial values for the simulation are , [E2F] = 0, [MiR449] = 0.004, [Myc] = 0.0280, [Cdk6] = 0.0090, [CycE] = 0, [Rb] = 2.9918, [PRb] = 0.0004, [RE] = 0.0157.
Figure 3.
Bifurcation diagram of [CycE-Cdk2] with S as a control parameter at .
Set the AUTO axes to run from 0 to 1.2 along the x-axis and from −0.001 to 0.22 along the y-axis. Initial values as in Fig. 2.
Figure 4.
Bifurcation diagram of [E2F] with S as a control parameter at .
Set the AUTO axes to run from 0 to 5 along the x-axis and from 0 to 0.75 along the y-axis. Initial values as in Fig. 2.
Figure 5.
Bifurcation diagram of [CycE-Cdk2] with as a control parameter at
.
Set the AUTO axes to run from 0 to 5 along the x-axis and from −0.001 to 0.13 along the y-axis. Initial values as in Fig. 2.
Figure 6.
Time courses of [E2F] and [CycE-Cdk2] at .
Assume initial conditions are [E2F] = 0, [MiR449] = 0, [Myc] = 0, [Cdk6] = 0, [CycE] = 0, [Rb] = 0.55, [PRb] = 0, [RE] = 0. Set the Viewaxes run from 0 to 200 along the x-axis and from 0 to 1.25 along the y-axis.(a) ; (b)
.
Figure 7.
Time courses of [E2F], [CycE-Cdk2] and [MiR449] at .
Assume initial conditions are [E2F] = 1.2, [MiR449] = 0, [Myc] = 0, [Cdk6] = 0, [CycE] = 0, [Rb] = 0.55, [PRb] = 0, [RE] = 0. (a) . Set the Viewaxes run from 0 to 200 along the x-axis and from 0 to 2 along the y-axis; (b)
. Set the Viewaxes run from 0 to 200 along the x-axis and from 0 to 1.7 along the y-axis.
Figure 8.
Bifurcation diagrams of [E2F] with as a control parameter.
Set the AUTO axes to run from 0 to 3 along the x-axis and from −0.01 to 1.2 along the y-axis. (a) with initial values as
, [E2F] = 1.1489, [MiR449] = 0, [Myc] = 1.0084, [Cdk6] = 0.2292, [CycE] = 0.2064, [Rb] = 0.0175, [PRb] = 2.5921, [RE] = 0.7793; (b)
with initial conditions as
, [E2F] = 1.1998, [MiR449] = 0, [Myc] = 1.2245, [Cdk6] = 0.2750, [CycE] = 0.2074, [Rb] = 0.0167, [PRb] = 2.6588, [RE] = 0.6489; (c)
with initial values as
, [E2F] = 1.2137, [MiR449] = 0, [Myc] = 1.2987, [Cdk6] = 0.2907, [CycE] = 0.2077, [Rb] = 0.0165, [PRb] = 2.6767, [RE] = 0.6136.
Figure 9.
Time courses of [E2F], [CycE-Cdk2] and [MiR449] at .
Assume initial conditions are [E2F] = 1.2, [MiR449] = 0, [Myc] = 0, [Cdk6] = 0, [CycE] = 0, [Rb] = 0.55, [PRb] = 0, [RE] = 0. (a) . Set the Viewaxes run from 0 to 150 along the x-axis and from 0 to 1.8 along the y-axis; (b)
. Set the Viewaxes run from 0 to 25 along the x-axis and from 0 to 3.3 along the y-axis.
Figure 10.
Bifurcation diagrams of [E2F] with inhibition rates of miR449 on three targets as control parameters.
Set up initial conditions as , [E2F] = 1.1489, [MiR449] = 61.9160, [Myc] = 1.0084, [Cdk6] = 0.2292, [CycE] = 0.2064, [Rb] = 0.0175, [PRb] = 2.5929, [RE] = 0.7793. (a) Bifurcation diagram of [E2F] with
as a control parameter at
and
. Set the AUTO axes to run from −1 to 25 along the x-axis and from −0.01 to 1.2 along the y-axis; (b) Bifurcation diagram of [E2F] with
as a control parameter at
and
. Set the AUTO axes to run from 0 to 0.3 along the x-axis and from −0.01 to 1.8 along the y-axis; (c) Bifurcation diagram of [E2F] with
as a control parameter at
and
. Set the AUTO axes to run from 0 to 5 along the x-axis and from −0.01 to 1.2 along the y-axis.