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The auxin-inducible degron 2 technology provides sharp degradation control in yeast, mammalian cells, and mice

2020· article· en· 574 citations· W3102624934 on OpenAlex· 10.1038/s41467-020-19532-z

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Canadian funderA Canadian agency funded it. The work may carry no Canadian affiliation at all.

No Canadian affiliation. An affiliation-only frame — the usual design — would never have seen this work. It is one of the works that make the case for inverting the frame.

Machine scores (provisional)

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

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Opus teacher head0.012
GPT teacher head0.253
Teacher spread
0.241 · how far apart the two teachers sit on this one work
Validation status
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Abstract

Protein knockdown using the auxin-inducible degron (AID) technology is useful to study protein function in living cells because it induces rapid depletion, which makes it possible to observe an immediate phenotype. However, the current AID system has two major drawbacks: leaky degradation and the requirement for a high dose of auxin. These negative features make it difficult to control precisely the expression level of a protein of interest in living cells and to apply this method to mice. Here, we overcome these problems by taking advantage of a bump-and-hole approach to establish the AID version 2 (AID2) system. AID2, which employs an OsTIR1(F74G) mutant and a ligand, 5-Ph-IAA, shows no detectable leaky degradation, requires a 670-times lower ligand concentration, and achieves even quicker degradation than the conventional AID. We demonstrate successful generation of human cell mutants for genes that were previously difficult to deal with, and show that AID2 achieves rapid target depletion not only in yeast and mammalian cells, but also in mice.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

The record

Venue
Nature Communications
Topic
Protein Degradation and Inhibitors
Field
Biochemistry, Genetics and Molecular Biology
Canadian institutions
Funders
Institute of GeneticsJapan Science and Technology AgencyJapan Agency for Medical Research and DevelopmentJapan Society for the Promotion of ScienceMinistry of Education, Culture, Sports, Science and TechnologyUniversity of DundeeAsahi Glass FoundationTakeda Science Foundation
Keywords
DegronGene knockdownMutantCell biologyYeastDegradation (telecommunications)Saccharomyces cerevisiaeFunction (biology)PhenotypeProtein degradationAuxinChemistryBiologyGeneBiochemistryComputer scienceUbiquitin ligaseUbiquitin
Has abstract in OpenAlex
yes