ArticleNature chemical biology2019
Design of fast proteolysis-based signaling and logic circuits in mammalian cells.
Article in Nature chemical biology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 106 papers.
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Who cites it
106 citing papers in PubMed.
- Beyond ER-Golgi trafficking: unconventional protein secretion as a new design frontier for synthetic secretion switches in mammalian cells.Communications biology · 2026Review
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- Molecular velcro for precision genome repair.Nature communications · 2026Article
- Monitoring in vivo transcription with synthetic serum markers.Nature communications · 2026Article
- Sensing and Reprogramming Surface Receptor Activation With Synthetic Transcriptional Circuits.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Engineering multiple levels of specificity in an RNA viral vector.Nature communications · 2026Article
- Identification and engineering of highly functional potyviral proteases in cells using co-evolutionary models.Nature communications · 2026Article
- Interrogating Physiological Functions with Light and Chemicals.Annual review of physiology · 2026Review
- A programmable genetic platform for engineering noninvasive biosensors.Science advances · 2026Article
- Leveraging Autonomous Biological Oscillators for Directed Evolution of Switchable Proteins.Advances in experimental medicine and biology · 2026Review
- Compact RNA sensors for increasingly complex functions of multiple inputs.Nature chemistry · 2025Article
- Boolean logic-gated protein presentation through autonomously compiled molecular topology.Nature chemical biology · 2025Article
- Regulation of therapeutic protein release in response to circadian biomarkers.Nature communications · 2025Article
- Synthetic protein degradation circuits using programmable cleavage and ligation by Sortase A.Nature communications · 2025Article
- Tunable, proteolytic dosage control of CRISPR-Cas systems enables precise gene therapy for dosage sensitive disorders.bioRxiv : the preprint server for biology · 2025Article
- A programmable genetic platform for engineering noninvasive biosensors.bioRxiv : the preprint server for biology · 2025Article
- Orthogonalized human protease control of secreted signals.Nature chemical biology · 2025Article
- Protease engineering: Approaches, tools, and emerging trends.Biotechnology advances · 2025Review
- Dissecting the effects of single amino acid substitutions in SARS-CoV-2 Mpro.Protein science : a publication of the Protein Society · 2025Article
- A generalizable approach for programming protease-responsive conformationally inhibited artificial transcriptional factors.Nature communications · 2025Article
46 more citing papers are in PubMed but not listed here.
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12 authors.
Funding
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 competitive displacement after proteolytic cleavage. This framework enabled the implementation of Boolean logic functions and signaling cascades in mammalian cells. The designed split-protease-cleavable orthogonal-CC-based (SPOC) logic circuits enable response to chemical or biological signals within minutes rather than hours and should be useful for diverse medical and nonmedical applications.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.