Evidence map›Paper›PMID 26214256›Full record

ArticleNature chemical biology2015

Tunable and reversible drug control of protein production via a self-excising degron.

Hokyung K Chung, Conor L Jacobs, Yunwen Huo, Jin Yang, Stefanie A Krumm, Richard K Plemper, Roger Y Tsien, Michael Z Lin

Open access · greenAbstract read
In one paragraph

Article in Nature chemical biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 146 papers.

0numbers the graph read from it
0cells of the map it votes in
146citing papers in PubMed
5.9field-weighted citation impact, top 3% 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

146 citing papers in PubMed, 233 citations in OpenAlex.

  1. Post-Translational Regulation Using Degrons in Ewing Sarcoma.Methods in molecular biology (Clifton, N.J.) · 2027
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  8. Humanized extracellular vesicles for efficient RNA delivery.Proceedings of the National Academy of Sciences of the United States of America · 2026
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  18. Humanized Extracellular Vesicles for Efficient RNA Delivery.bioRxiv : the preprint server for biology · 2025
    Article
  19. Article
  20. Article

86 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

8 authors at 3 institutions in 1 country.

Hokyung K ChungDepartment of Biology, Stanford University, Stanford, California, USA.
Conor L JacobsDepartment of Biology, Stanford University, Stanford, California, USA.
Yunwen HuoDepartment of Pediatrics, Stanford University, Stanford, California, USA.
Jin YangDepartment of Pharmacology, University of California, San Diego, La Jolla, California, USA.
Stefanie A KrummDepartment of Pediatrics, Emory University, Atlanta, Georgia, USA.
Richard K Plemper1] Department of Pediatrics, Emory University, Atlanta, Georgia, USA. [2] Institute for Biomedical Sciences, Georgia State University, Atlanta, Georgia, USA.
Roger Y Tsien1] Department of Pharmacology, University of California, San Diego, La Jolla, California, USA. [2] Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, California, USA. [3] Howard Hughes Medical Institute, University of California, San Diego, La Jolla, California, USA.
Michael Z Lin1] Department of Pediatrics, Stanford University, Stanford, California, USA. [2] Department of Bioengineering, Stanford University, Stanford, California, USA.
Stanford University · USEmory University · USUniversity of California, San Diego · US

Funding

TRAINING & OUTREACH COREP50GM107615 · NIGMS · STANFORD UNIVERSITY · PI COVERT, MARKUS W · 2013 to 2017
$10.9M
Identification and Pre-Clinical Evaluation of Measles Virus InhibitorsR01AI071002 · NIAID · GEORGIA STATE UNIVERSITY · PI PLEMPER, RICHARD K. · 2006 to 2022
$6.6M
Novel Therapeutics against Respiratory Syncytial Virus InfectionR01HD079327 · NICHD · GEORGIA STATE UNIVERSITY · PI PLEMPER, RICHARD K. · 2014 to 2018
$2.8M
Cryo-Electron and Biochemical Anaysis of Native Paramyxovirus Fusion ComplexesR01AI083402 · NIAID · GEORGIA STATE UNIVERSITY · PI PLEMPER, RICHARD K. · 2011 to 2015
$1.7M
A Molecular Tag for Drug-Regulated Synthesis of Specific ProteinsR01GM098734 · NIGMS · STANFORD UNIVERSITY · PI LIN, MICHAEL Z. · 2011 to 2014
$1.2M
Identification and Hit-to-Lead Development of Influenza A Virus InhibitorsR21AI119196 · NIAID · GEORGIA STATE UNIVERSITY · PI PLEMPER, RICHARD K. · 2015 to 2016
$436k
NIAID NIH HHS 5R01AI071002NIAID NIH HHS 5R01AI083402NIAID NIH HHS R01 AI071002NIAID NIH HHS R01 AI083402NIAID NIH HHS R21 AI119196NICHD NIH HHS R01 HD079327NIGMS NIH HHS 5R01GM098734NIGMS NIH HHS P50 GM107615NIGMS NIH HHS R01 GM098734
6 · The paper itself

Abstract

An effective method for direct chemical control over the production of specific proteins would be widely useful. We describe small molecule-assisted shutoff (SMASh), a technique in which proteins are fused to a degron that removes itself in the absence of drug, resulting in the production of an untagged protein. Clinically tested HCV protease inhibitors can then block degron removal, inducing rapid degradation of subsequently synthesized copies of the protein. SMASh allows reversible and dose-dependent shutoff of various proteins in multiple mammalian cell types and in yeast. We also used SMASh to confer drug responsiveness onto an RNA virus for which no licensed inhibitors exist. As SMASh does not require the permanent fusion of a large domain, it should be useful when control over protein production with minimal structural modification is desired. Furthermore, as SMASh involves only a single genetic modification and does not rely on modulating protein-protein interactions, it should be easy to generalize to multiple biological contexts.

Indexed as

Amino Acid SequenceAnimalsBacterial ProteinsBinding SitesCarrier ProteinsChlorocebus aethiopsDEAD-box RNA HelicasesGene Expression RegulationHEK293 CellsHeLa CellsHepacivirusHumansIntracellular Signaling Peptides and ProteinsIsoquinolinesLuminescent ProteinsMolecular Sequence DataasunaprevirBacterial ProteinsCarrier ProteinsDEAD-box RNA HelicasesIntracellular Signaling Peptides and ProteinsIsoquinolinesLuminescent ProteinsNS3 protein, hepatitis C virusNS4A cofactor peptide, Hepatitis C virusNucleoside-TriphosphataseProtease InhibitorsRecombinant Fusion ProteinsSerine EndopeptidasesSulfonamidesViral Nonstructural ProteinsViral Proteasesyellow fluorescent protein, Bacteria

Identifiers

PMID26214256
PMCPMC4543534
OpenAlexW1043004949

What OpenQuestion holds

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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.