The complexity of multisite phosphorylation mechanisms in regulating nuclear localization signals (NLSs) and nuclear export signals (NESs) is not understood, and its potential has not been used in synthetic biology. The nucleocytoplasmic shuttling of many proteins is regulated by cyclin-dependent kinases (CDKs) that rely on multisite phosphorylation patterns and short linear motifs (SLiMs) to dynamically control proteins in the cell cycle. We studied the role of motif patterns in nucleocytoplasmic shuttling using sensors based on the CDK targets Dna2, Psy4, and Mcm2/3 of Saccharomyces cerevisiae. We designed multisite phosphorylation modules by rearranging phosphorylation sites, cyclin-specific SLiMs, phospho-priming, phosphatase specificity, and NLS/NES phospho-regulation and obtained very different substrate localization dynamics. These included ultrasensitive responses with and without a delay, graded responses, and different homeostatic plateaus. Thus, CDK can do much more than trigger sequential switches during the cell cycle as it can drive complex patterns of protein localization and activity by using multisite phosphorylation networks.
Pubmed ID: 35977012 RIS Download
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Database dedicated to the analysis of the genome of Escherichia coli. Its purpose is to collate and integrate various aspects of the genomic information from E. coli, the paradigm of Gram-negative bacteria. Colibri provides a complete dataset of DNA and protein sequences derived from the paradigm strain E. coli K-12, linked to the relevant annotations and functional assignments. It allows one to easily browse through these data and retrieve information, using various criteria (gene names, location, keywords, etc.). The data contained in Colibri originates from two major sources of information, the reference genomic DNA sequence from the E. coli Genome Project and the feature annotations from the EcoGene data collection.
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View all literature mentionsThis monoclonal targets HA.11
View all literature mentionsThis monoclonal targets HA.11
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