Design of fast proteolysis-based signaling and logic circuits in mammalian cells.

ABSTRACT: Cellular signal transduction is predominantly based on protein interactions and their post-translational modifications, which enable a fast response to input signals. Owing to difficulties in designing new unique protein-protein interactions, designed cellular logic has focused on transcriptional regulation; however, that process has a substantially slower response, because it requires transcription and translation. Here, we present de novo design of modular, scalable signaling pathways based on proteolysis and designed coiled coils (CC) and implemented in mammalian cells. A set of split proteases with highly specific orthogonal cleavage motifs was constructed and combined with strategically positioned cleavage sites and designed orthogonal CC dimerizing domains with tunable affinity for c

SUBMITTER: Fink T 

PROVIDER: S-EPMC7069760 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature