Integration of Dynamic Protein Localization, Proteolysis, and Phospho-signaling Drives Transcriptional Cell Cycle Circuitry

Lucy Shapiro Associate Chair, Department of Developmental Biology, Stanford University School of Medicine

"Integration of Dynamic Protein Localization, Proteolysis, and Phospho-signaling Drives Transcriptional Cell Cycle Circuitry"

Abstract: The bacterial cell cycle involves a choreographed cast of proteins that enter and leave the cell on cue to take up designated positions in the cell and perform their roles in concert with other proteins. The execution of the cell cycle is driven by a small group of master regulatory proteins organized into a cyclical genetic circuit. A central player is the CtrA master regulator that directly controls 95 proteins. Asymmetric regulation of CtrA stability and phosphorylation in the Caulobacter daughter cells is the central event establishing asymmetry and the different cell fates of the two daughters. The mechanisms used to accomplish this asymmetry involve dynamic positioning of multiple proteins to one pole or the other, highly regulated proteolytic events, a complex network of phospho-signaling reactions distributed in space and time, and tight DNA methylation-based coupling between regulatory gene expression and progression of chromosome replication.