Robust and tunable signal processing in mammalian cells via engineered covalent modification cycles.

ABSTRACT: Engineered signaling networks can impart cells with new functionalities useful for directing differentiation and actuating cellular therapies. For such applications, the engineered networks must be tunable, precisely regulate target gene expression, and be robust to perturbations within the complex context of mammalian cells. Here, we use bacterial two-component signaling proteins to develop synthetic phosphoregulation devices that exhibit these properties in mammalian cells. First, we engineer a synthetic covalent modification cycle based on kinase and phosphatase proteins derived from the bifunctional histidine kinase EnvZ, enabling analog tuning of gene expression via its response regulator OmpR. By regulating phosphatase expression with endogenous miRNAs, we demonstrate cell-type speci

SUBMITTER: Jones RD 

PROVIDER: S-EPMC8971529 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature