Molecular interaction map of the p53 and Mdm2 logic elements, which control the Off–On switch of p53 in response to DNA damage

The molecular network that controls responses to genotoxic stress is centered at p53 and Mdm2. Recent findings have shown this network to be more complex than previously envisioned. Using a notation specifically designed for circuit diagram-like representations of bioregulatory networks, we have prepared an updated molecular interaction map of the immediate connections of p53 and Mdm2, which are described as logic elements of the network. We use the map as the basis for a comprehensive review of current concepts of signal processing by these logic elements (an interactive version of the maps—eMIMs can be examined at http://discover.nci.nih.gov/mim). We also used molecular interaction maps to propose a p53 Off–On switch in response to DNA damage.