Evidence map›Paper›PMID 34865044›Full record

ArticleGenetics2022

The auxin-inducible degron 2 (AID2) system enables controlled protein knockdown during embryogenesis and development in Caenorhabditis elegans.

Takefumi Negishi, Saho Kitagawa, Natsumi Horii, Yuka Tanaka, Nami Haruta, Asako Sugimoto, Hitoshi Sawa, Ken-Ichiro Hayashi, Masahiko Harata, Masato T Kanemaki

Open access · bronzeAbstract read
In one paragraph

Article in Genetics, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.

0numbers the graph read from it
0cells of the map it votes in
37citing papers in PubMed
3.1field-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

37 citing papers in PubMed, 59 citations in OpenAlex.

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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

10 authors at 3 institutions in 1 country.

Takefumi NegishiMulticellular Organization Laboratory, Department of Gene Function and Phenomics, National Institute of Genetics, Research Organization of Information and Systems (ROIS), Mishima, Shizuoka 411-8540, Japan.
Saho KitagawaLaboratory of Molecular Biology, Division of Life Science, Graduate School of Agricultural Science, Tohoku University, Aoba-ku, Sendai 980-0845, Japan.
Natsumi HoriiLaboratory of Molecular Biology, Division of Life Science, Graduate School of Agricultural Science, Tohoku University, Aoba-ku, Sendai 980-0845, Japan.
Yuka TanakaDepartment of Biochemistry, Okayama University of Science, Okayama 700-0005, Japan.
Nami HarutaLaboratory of Developmental Dynamics, Department of Integrative Life Sciences, Graduate School of Life Sciences, Tohoku University, Aoba-ku, Sendai 980-8577, Japan.
Asako SugimotoLaboratory of Developmental Dynamics, Department of Integrative Life Sciences, Graduate School of Life Sciences, Tohoku University, Aoba-ku, Sendai 980-8577, Japan.
Hitoshi SawaMulticellular Organization Laboratory, Department of Gene Function and Phenomics, National Institute of Genetics, Research Organization of Information and Systems (ROIS), Mishima, Shizuoka 411-8540, Japan.
Ken-Ichiro HayashiDepartment of Biochemistry, Okayama University of Science, Okayama 700-0005, Japan.
Masahiko HarataLaboratory of Molecular Biology, Division of Life Science, Graduate School of Agricultural Science, Tohoku University, Aoba-ku, Sendai 980-0845, Japan.
Masato T KanemakiDepartment of Genetics, School of Life Science, SOKENDAI (The Graduate University for Advanced Studies), Mishima, Shizuoka 411-8540, Japan.ORCID 0000-0002-7657-1649
Tohoku University · JPNational Institute of Genetics · JPOkayama University of Science · JP

Funding

Enhancing and expanding the CGC Strain CollectionP40OD010440 · OD · UNIVERSITY OF MINNESOTA · PI Aric L Daul, Ann E. Rougvie · 2012 to 2026
$7.5M
NIH HHS P40 OD010440
6 · The paper itself

Abstract

Targeted protein degradation using the auxin-inducible degron (AID) system is garnering attention in the research field of Caenorhabditis elegans, because of the rapid and efficient target depletion it affords, which can be controlled by treating the animals with the phytohormone auxin. However, the current AID system has drawbacks, i.e., leaky degradation in the absence of auxin and the requirement for high auxin doses. Furthermore, it is challenging to deplete degron-fused proteins in embryos because of their eggshell, which blocks auxin permeability. Here, we apply an improved AID2 system utilizing AtTIR1(F79G) and 5-phenyl-indole-3-acetic acid (5-Ph-IAA) to C. elegans and demonstrated that it confers better degradation control vs the previous system by suppressing leaky degradation and inducing sharp degradation using 1,300-fold lower 5-Ph-IAA doses. We successfully degraded the endogenous histone H2A.Z protein fused to an mAID degron and disclosed its requirement in larval growth and reproduction, regardless of the presence of maternally inherited H2A.Z molecules. Moreover, we developed an eggshell-permeable 5-Ph-IAA analog, 5-Ph-IAA-AM, that affords an enhanced degradation in laid embryos. Our improved system will contribute to the disclosure of the roles of proteins in C. elegans, in particular those that are involved in embryogenesis and development, through temporally controlled protein degradation.

Indexed as

Caenorhabditis elegansIndoleacetic AcidsAnimalsEmbryonic DevelopmentProteinsProteolysisIndoleacetic AcidsProteins5-Ph-IAA5-Ph-IAA-AMAIDauxinCaenorhabditis elegansdegronhistone H2A.Zprotein knockdowntargeted protein degradation

Identifiers

PMID34865044
PMCPMC9208642
OpenAlexW4200300327

What OpenQuestion holds

Textmetadata
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.