This model is a refined version of the logical model of the p53-mdm2 network described in Fig. 5a of Abou-Jaoudé et al. [1].
The regulatory graph describes the interactions between protein p53, the ubiquitin ligase Mdm2 in its nuclear and cytoplasmic forms, and DNA damage. It relies on biological data taken from literature.
In short, the nuclear component of Mdm2 down-regulates the level of active p53. This occurs both by accelerating p53 degradation through ubiquitination and by blocking the transcriptional activity of p53.
Protein p53 plays a dual role. It activates the expression of Mdm2 thereby up-regulating the level of cytoplasmic Mdm2, and down-regulates the level of nuclear Mdm2 by inhibiting Mdm2 nuclear translocation through inactivation of the kinase Akt.
DNA damage has a negative influence on the level of nuclear Mdm2, by accelerating its degradation through ATM-mediated phosphorylation and auto-ubiquitination.
Damage-induced Mdm2 destabilization enables p53 to accumulate and remain active.
Finally, high levels of p53 promote damage repair by inducing the synthesis of DNA repair proteins.
