Evidence map›Paper›PMID 21725303›Full record

ArticleNature chemical biology2011

Small-molecule displacement of a cryptic degron causes conditional protein degradation.

Kimberly M Bonger, Ling-chun Chen, Corey W Liu, Thomas J Wandless

Open access · greenAbstract read
In one paragraph

Article in Nature chemical biology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 108 papers.

0numbers the graph read from it
0cells of the map it votes in
108citing papers in PubMed
4.1field-weighted citation impact, top 5% 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

108 citing papers in PubMed, 205 citations in OpenAlex.

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

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

4 authors at 2 institutions in 1 country.

Kimberly M BongerDepartment of Chemical & Systems Biology, Stanford University, Stanford, California, USA.
Ling-chun Chen
Corey W Liu
Thomas J Wandless
Stanford University · USResonance Research (United States) · US

Funding

Novel Molecules as In Vivo Biological ProbesR01GM073046 · NIGMS · STANFORD UNIVERSITY · PI WANDLESS, THOMAS JAMES · 2006 to 2017
$3.6M
NIGMS NIH HHS GM073046NIGMS NIH HHS R01 GM073046
6 · The paper itself

Abstract

The ability to rapidly regulate the functions of specific proteins in living cells is a valuable tool for biological research. Here we describe a new technique by which the degradation of a specific protein is induced by a small molecule. A protein of interest is fused to a ligand-induced degradation (LID) domain, resulting in the expression of a stable and functional fusion protein. The LID domain is comprised of the FK506- and rapamycin-binding protein (FKBP) and a 19-amino-acid degron fused to the C terminus of FKBP. In the absence of the small molecule Shield-1, the degron is bound to the FKBP fusion protein and the protein is stable. When present, Shield-1 binds tightly to FKBP, displacing the degron and inducing rapid and processive degradation of the LID domain and any fused partner protein. Structure-function studies of the 19-residue peptide showed that a 4-amino-acid sequence within the peptide is responsible for degradation.

Indexed as

Protein DenaturationAmino Acid SequenceAnimalsBacterial ProteinsCatalytic DomainCell LineCloning, MolecularGene Expression RegulationLuminescent ProteinsMiceModels, MolecularMorpholinesPeptidesProtein Structure, TertiaryTacrolimus Binding ProteinsBacterial ProteinsLuminescent ProteinsMorpholinesPeptidesShield-1 compoundTacrolimus Binding Proteinsyellow fluorescent protein, Bacteria

Identifiers

PMID21725303
PMCPMC3139708
OpenAlexW2078434863

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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.