Figure 1.Cdk2 controls suppression of cellular senescence by Myc.
(A) Apoptosis and senescence are two intrinsic tumor suppressor
mechanism that are triggered by oncogenic signals. Myc and Ras contributes
to this by inducing apoptosis and senescence, respectively. However,
activated Myc and Ras are together sufficient to transform primary rodent
cells for unclear reasons. We recently found that while Ras suppresses
Myc-induced apoptosis, Myc is able to suppress Ras-induced senescence,
thereby together overcoming two main barriers of tumorigenesis. In order
to suppress senescence Myc needs to be phosphorylated by Cdk2. Since Myc
stimulates Cdk2 activity, Myc and Cdk2 are involved in an auto-stimulatory
loop generating suppression of senescence. (B) Depletion or
inhibition of Cdk2 abolishes to ability of Myc to suppress senescence and
switches Myc into an activator of senescence, thereby inhibiting tumor
development or maintenance.
