| Title: | Feedforward regulation ensures stability and rapid reversibility of a cellular state |
| Address: | "Department of Biology, Stanford University, Stanford, CA 94305, USA" |
| DOI: | 10.1016/j.molcel.2013.04.014 |
| ISSN/ISBN: | 1097-4164 (Electronic) 1097-2765 (Print) 1097-2765 (Linking) |
| Abstract: | "Cellular transitions are important for all life. Such transitions, including cell fate decisions, often employ positive feedback regulation to establish and stabilize new cellular states. However, positive feedback is unlikely to underlie stable cell-cycle arrest in yeast exposed to mating pheromone because the signaling pathway is linear, rather than bistable, over a broad range of extracellular pheromone concentration. We show that the stability of the pheromone-arrested state results from coherent feedforward regulation of the cell-cycle inhibitor Far1. This network motif is effectively isolated from the more complex regulatory network in which it is embedded. Fast regulation of Far1 by phosphorylation allows rapid cell-cycle arrest and reentry, whereas slow Far1 synthesis reinforces arrest. We expect coherent feedforward regulation to be frequently implemented at reversible cellular transitions because this network motif can achieve the ostensibly conflicting aims of arrest stability and rapid reversibility without loss of signaling information" |
| Keywords: | "Algorithms Cell Cycle Checkpoints Cyclin-Dependent Kinase Inhibitor Proteins/genetics/metabolism Cyclins/metabolism *Feedback, Physiological MAP Kinase Signaling System Models, Biological Protein Precursors/physiology Protein Stability Saccharomyces cerev;" |
| Notes: | "MedlineDoncic, Andreas Skotheim, Jan M eng R01 GM092925/GM/NIGMS NIH HHS/ GM092925/GM/NIGMS NIH HHS/ Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't 2013/05/21 Mol Cell. 2013 Jun 27; 50(6):856-68. doi: 10.1016/j.molcel.2013.04.014. Epub 2013 May 16" |
