A synthetic biology approach reveals diverse and dynamic CDK response profiles via multisite phosphorylation of NLS-NES modules

• DOI: 10.1126/sciadv.abp8992
• Publication Date: 2022-08-17T17:57:37Z
• Authors: Ilona Faustova; Mihkel Örd; Viacheslav Kiselev; Dmytro Fedorenko; Irina Borovko; Dags Macs; Kaur Pääbo; Marko Lõoke; Mart Loog
• Keywords: NLS

The complexity of multisite phosphorylation mechanisms in regulating nuclear localization signals (NLSs) and export (NESs) is not understood, its potential has been used synthetic biology. nucleocytoplasmic shuttling many proteins regulated by cyclin-dependent kinases (CDKs) that rely on patterns short linear motifs (SLiMs) to dynamically control the cell cycle. We studied role motif using sensors based CDK targets Dna2, Psy4, Mcm2/3 Saccharomyces cerevisiae. designed modules rearranging sites, cyclin-specific SLiMs, phospho-priming, phosphatase specificity, NLS/NES phospho-regulation obtained very different substrate dynamics. These included ultrasensitive responses with without a delay, graded responses, homeostatic plateaus. Thus, can do much more than trigger sequential switches during cycle as it drive complex protein activity networks.