Revealing static and dynamic modular architecture of the eukaryotic protein interaction network

In an effort to understand the dynamic organization of the protein interaction network and its role in the regulation of cell behavior, positioning of proteins into specific network localities was studied with respect to their expression dynamics. First, we find that constitutively expressed and dynamically co-regulated proteins cluster in distinct functionally specialized network neighborhoods to form static and dynamic functional modules, respectively. Then, we show that whereas dynamic modules are mainly responsible for condition-dependent regulation of cell behavior, static modules provide robustness to the cell against genetic perturbations or protein expression noise, and therefore may act as buffers of evolutionary as well as population variations in cell behavior. Observations in this study refine the previously proposed model of dynamic modularity in the protein interaction network, and propose a link between the evolution of gene expression regulation and biological robustness.