ArticleNature chemical biology2017
A computationally engineered RAS rheostat reveals RAS-ERK signaling dynamics.
Article in Nature chemical biology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 27 citations in OpenAlex.
- Review
- Identification of affinity-optimized peptide binders of a viral protease for chemical genetic applications.Bioorganic & medicinal chemistry letters · 2026Article
- HDAC11 Deacetylates BRAF to Regulate Kinase Activity and Cell Proliferation.ACS chemical biology · 2025Article
- A Modular Platform for the Optogenetic Control of Small GTPase Activity in Living Cells Reveals Long-Range RhoA Signaling.bioRxiv : the preprint server for biology · 2025Article
- Methods for Controlling Small GTPase Activity.Chembiochem : a European journal of chemical biology · 2025Review
- Computationally designed sensors detect endogenous Ras activity and signaling effectors at subcellular resolution.Nature biotechnology · 2024Article
- Standardized Parts for Activation of Small GTPase Signaling in Living Cells.Angewandte Chemie (International ed. in English) · 2024Article
- Standardized Parts for Activation of Small GTPase Signaling in Living Cells.bioRxiv : the preprint server for biology · 2024Article
- Fluorescent Biosensor for Measuring Ras Activity in Living Cells.Journal of the American Chemical Society · 2022Article
- "Examining RAS pathway rewiring with a chemically inducible activator of RAS".Small GTPases · 2020Article
- Beyond natural: synthetic expansions of botanical form and function.The New phytologist · 2020Review
- Multi-input chemical control of protein dimerization for programming graded cellular responses.Nature biotechnology · 2019Article
- Optogenetic Repressors of Gene Expression in Yeasts Using Light-Controlled Nuclear Localization.Cellular and molecular bioengineering · 2019Article
- A Chemically Disrupted Proximity System for Controlling Dynamic Cellular Processes.Journal of the American Chemical Society · 2019Article
- Precision Control of CRISPR-Cas9 Using Small Molecules and Light.Biochemistry · 2019Review
- Activation of Rho Family GTPases by Small Molecules.ACS chemical biology · 2018Article
- Rheostatic Control of Cas9-Mediated DNA Double Strand Break (DSB) Generation and Genome Editing.ACS chemical biology · 2018Article
- Rapidly inducible Cas9 and DSB-ddPCR to probe editing kinetics.Nature methods · 2017Article
Corrections and comments
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Authors and funding
13 authors at 3 institutions in 1 country.
Funding
Abstract
Synthetic protein switches controlled with user-defined inputs are powerful tools for studying and controlling dynamic cellular processes. To date, these approaches have relied primarily on intermolecular regulation. Here we report a computationally guided framework for engineering intramolecular regulation of protein function. We utilize this framework to develop chemically inducible activator of RAS (CIAR), a single-component RAS rheostat that directly activates endogenous RAS in response to a small molecule. Using CIAR, we show that direct RAS activation elicits markedly different RAS-ERK signaling dynamics from growth factor stimulation, and that these dynamics differ among cell types. We also found that the clinically approved RAF inhibitor vemurafenib potently primes cells to respond to direct wild-type RAS activation. These results demonstrate the utility of CIAR for quantitatively interrogating RAS signaling. Finally, we demonstrate the general utility of our approach in design of intramolecularly regulated protein tools by applying it to the Rho family of guanine nucleotide exchange factors.
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Registered trials
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.