Evidence map›Paper›PMID 32555187›Full record

ArticleNature communications2020

Phosphoregulated orthogonal signal transduction in mammalian cells.

Leo Scheller, Marc Schmollack, Adrian Bertschi, Maysam Mansouri, Pratik Saxena, Martin Fussenegger

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
3.8field-weighted citation impact, top 7% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

18 citing papers in PubMed, 33 citations in OpenAlex.

  1. Human Synthetic Biology and Programmable Gene Regulation Control.Annual review of genomics and human genetics · 2025
    Review
  2. Engineering signalling pathways in mammalian cells.Nature biomedical engineering · 2024
    Review
  3. Perspectives on Synthetic Protein Circuits in Mammalian Cells.Current opinion in biomedical engineering · 2024
    Article
  4. Review
  5. Article
  6. Review
  7. Engineering synthetic phosphorylation signaling networks in human cells.bioRxiv : the preprint server for biology · 2023
    Article
  8. Rational design of small-molecule responsive protein switches.Protein science : a publication of the Protein Society · 2023
    Review
  9. Article
  10. Review
  11. Article
  12. The evolution of synthetic receptor systems.Nature chemical biology · 2022
    Review
  13. Article
  14. Review
  15. Review
  16. Review
  17. Article
  18. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors at 2 institutions in 2 countries.

Leo SchellerDepartment of Biosystems Science and Engineering, ETH Zurich, Mattenstrasse 26, CH-4058, Basel, Switzerland.ORCID http://orcid.org/0000-0003-2490-4015
Marc SchmollackDepartment of Biosystems Science and Engineering, ETH Zurich, Mattenstrasse 26, CH-4058, Basel, Switzerland.
Adrian BertschiDepartment of Biosystems Science and Engineering, ETH Zurich, Mattenstrasse 26, CH-4058, Basel, Switzerland.ORCID http://orcid.org/0000-0002-1981-1618
Maysam MansouriDepartment of Biosystems Science and Engineering, ETH Zurich, Mattenstrasse 26, CH-4058, Basel, Switzerland.
Pratik SaxenaDepartment of Biosystems Science and Engineering, ETH Zurich, Mattenstrasse 26, CH-4058, Basel, Switzerland.
Martin FusseneggerDepartment of Biosystems Science and Engineering, ETH Zurich, Mattenstrasse 26, CH-4058, Basel, Switzerland. martin.fussenegger@bsse.ethz.ch.ORCID http://orcid.org/0000-0001-8545-667X
ETH Zurich · CHUniversity of Basel · CH

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Orthogonal tools for controlling protein function by post-translational modifications open up new possibilities for protein circuit engineering in synthetic biology. Phosphoregulation is a key mechanism of signal processing in all kingdoms of life, but tools to control the involved processes are very limited. Here, we repurpose components of bacterial two-component systems (TCSs) for chemically induced phosphotransfer in mammalian cells. TCSs are the most abundant multi-component signal-processing units in bacteria, but are not found in the animal kingdom. The presented phosphoregulated orthogonal signal transduction (POST) system uses induced nanobody dimerization to regulate the trans-autophosphorylation activity of engineered histidine kinases. Engineered response regulators use the phosphohistidine residue as a substrate to autophosphorylate an aspartate residue, inducing their own homodimerization. We verify this approach by demonstrating control of gene expression with engineered, dimerization-dependent transcription factors and propose a phosphoregulated relay system of protein dimerization as a basic building block for next-generation protein circuits.

Indexed as

Signal TransductionAdipose TissueAnimalsBacterial ProteinsFemaleGene Expression RegulationHEK293 CellsHistidineHistidine KinaseHumansInduced Pluripotent Stem CellsMesenchymal Stem CellsMiddle AgedNanotechnologyPhosphorylationProtein DomainsBacterial ProteinsHistidineHistidine KinaseTranscription Factors

Identifiers

PMID32555187
PMCPMC7303213
OpenAlexW3036774895

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.