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Bioregulatory networks are notoriously difficult to diagram. However, it would be very handy to have a generally understood notation, as in electronic circuit diagrams. The cover picture illustrates a proposed notation, described by Kohn et al. in this issue. The picture shows how multiple signaling pathways from one point to another in a network can be depicted on the same diagram. The diagram is a canonical molecular interaction map in which four signaling paths from ATM to p53 are highlighted: (a) a path via phosphorylation of p53 that inhibits binding of Mdm2 and consequently inhibits p53 degradation; (b) a path via the same phosphorylation of p53, but leading to p53 acetylation and consequent increased promoter binding and transcriptional activity; (c) a path via phosphorylation of Mdm2 that inhibits binding to p53; (d) a path via phosphorylation of Chk2, leading to phosphorylation of p53, inhibition of Mdm2 binding, and inhibition of p53 degradation. Two additional pathways (not shown) could be highlighted on the map: a path that starts out the same as (d), but enhances p53's transcriptional activity as in (b); and a path via phosphorylation of c-Abl, leading to phosphorylation of Mdm2, inhibition of p53 binding, and inhibition of p53 degradation. All six pathways lead from a given stimulus (ATM activation) to the same effect (p53 up-regulation). Multiple paths operating simultaneously to a given effect may help make cell responses robust in the face of diverse circumstances. See the full article by Kohn et al. on p. 1 in this issue of MBC. (Image: Kurt W. Kohn, National Cancer Institute)

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