| Title: | Switch-like Transitions Insulate Network Motifs to Modularize Biological Networks |
| Author(s): | Atay O; Doncic A; Skotheim JM; |
| Address: | "Department of Biology, Stanford University, Stanford, CA 94305, USA. Department of Biology, Stanford University, Stanford, CA 94305, USA. Electronic address: skotheim@stanford.edu" |
| DOI: | 10.1016/j.cels.2016.06.010 |
| ISSN/ISBN: | 2405-4712 (Print) 2405-4720 (Electronic) 2405-4712 (Linking) |
| Abstract: | "Cellular decisions are made by complex networks that are difficult to analyze. Although it is common to analyze smaller sub-networks known as network motifs, it is unclear whether this is valid, because these motifs are embedded in complex larger networks. Here, we address the general question of modularity by examining the S. cerevisiae pheromone response. We demonstrate that the feedforward motif controlling the cell-cycle inhibitor Far1 is insulated from cell-cycle dynamics by the positive feedback switch that drives reentry to the cell cycle. Before cells switch on positive feedback, the feedforward motif model predicts the behavior of the larger network. Conversely, after the switch, the feedforward motif is dismantled and has no discernable effect on the cell cycle. When insulation is broken, the feedforward motif no longer predicts network behavior. This work illustrates how, despite the interconnectivity of networks, the activity of motifs can be insulated by switches that generate well-defined cellular states" |
| Keywords: | "Algorithms *Cell Cycle Cyclin-Dependent Kinase Inhibitor Proteins Feedback Feedback, Physiological Gene Regulatory Networks Models, Biological Saccharomyces cerevisiae Saccharomyces cerevisiae Proteins;" |
| Notes: | "MedlineAtay, Oguzhan Doncic, Andreas Skotheim, Jan M eng P50 GM107615/GM/NIGMS NIH HHS/ R01 GM092925/GM/NIGMS NIH HHS/ Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't 2016/07/28 Cell Syst. 2016 Aug; 3(2):121-132. doi: 10.1016/j.cels.2016.06.010. Epub 2016 Jul 21" |
