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 ). We also used molecular interaction maps to propose a p53 Off-On switch in response to DNA damage.
Kohn
Kurt W
KW
Laboratory of Molecular Pharmacology, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD 20892, USA. kohnk@dc37a.nci.nih.gov
Pommier
Yves
Y
D017209:Apoptosis / Q000502:physiology; D064007:Ataxia Telangiectasia Mutated Proteins; D018797:Cell Cycle Proteins / Q000378:metabolism; D064447:Checkpoint Kinase 2; D004247:DNA / Q000378:metabolism*; D004249:DNA Damage; D004268:DNA-Binding Proteins / Q000378:metabolism; D016193:G1 Phase / Q000502:physiology; D008954:Models, Biological; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D025941:Protein Interaction Mapping; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D051736:Proto-Oncogene Proteins c-mdm2; D016196:S Phase / Q000502:physiology; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000378:metabolism
D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; D004247:DNA; D051736:Proto-Oncogene Proteins c-mdm2; D064447:Checkpoint Kinase 2; D064007:Ataxia Telangiectasia Mutated Proteins; D017346:Protein Serine-Threonine Kinases