Model validation using robustness analysis 205
This positive feedback loop might represent in a simplified manner the actio n
of additional p53 system components, which have a total upregulating effect
on p53. The se mo de ls include both linear positive regulation (model V) and
nonlinear regulation based o n a sa turating function (model II). Models I–V,
although differing in detail, all rely on a single negative feedback loop. The
last model (VI) considered in the study propo ses a novel checkpoint mech-
anism, which uses two ne gative feedba ck loops, one direct feedback and one
longer loop that impinges on an upstr eam regulator of p53. In this model,
a protein downstream of p53 inhibits a signaling protein that is upstream of
p53.
In order to discriminate ...