Chk2 molecular interaction map and rationale for Chk2 inhibitors.

To organize the rapidly accumulating information on bioregulatory networks related to the histone gamma-H2AX-ATM-Chk2-p53-Mdm2 pathways in concise and unambiguous diagrams, we used the molecular interaction map notation (http://discover.nci.nih.gov/min). Molecular interaction maps are particularly useful for networks that include protein-protein binding and posttranslational modifications (e.g., phosphorylation). Both are important for nearly all of the proteins involved in DNA double-strand break signaling. Visualizing the regulatory circuits underlying cellular signaling may help identify key regulatory reactions and defects that can serve as targets for anticancer drugs.