Evidence map›Paper›PMID 33025907›Full record

ArticleeLife2020

Feedback control of Wnt signaling based on ultrastable histidine cluster co-aggregation between Naked/NKD and Axin.

Melissa V Gammons, Miha Renko, Joshua E Flack, Juliusz Mieszczanek, Mariann Bienz

Abstract read
In one paragraph

Article in eLife, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
–field-weighted citation impact
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

7 citing papers in PubMed.

  1. Article
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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

5 authors.

Melissa V Gammons *MRC Laboratory of Molecular Biology, Cambridge Biomedical Campus, Cambridge, United Kingdom.ORCID 0000-0001-9661-9331
Miha Renko *MRC Laboratory of Molecular Biology, Cambridge Biomedical Campus, Cambridge, United Kingdom.
Joshua E Flack *MRC Laboratory of Molecular Biology, Cambridge Biomedical Campus, Cambridge, United Kingdom.
Juliusz Mieszczanek *MRC Laboratory of Molecular Biology, Cambridge Biomedical Campus, Cambridge, United Kingdom.
Mariann BienzMRC Laboratory of Molecular Biology, Cambridge Biomedical Campus, Cambridge, United Kingdom.ORCID 0000-0002-7170-8706

Funding

Cancer Research UK 24639Cancer Research UK C7379/A24639Medical Research Council MC_U105192713Medical Research Council U105192713
6 · The paper itself

Abstract

Feedback control is a universal feature of cell signaling pathways. Naked/NKD is a widely conserved feedback regulator of Wnt signaling which controls animal development and tissue homeostasis. Naked/NKD destabilizes Dishevelled, which assembles Wnt signalosomes to inhibit the β-catenin destruction complex via recruitment of Axin. Here, we discover that the molecular mechanism underlying Naked/NKD function relies on its assembly into ultra-stable decameric core aggregates via its conserved C-terminal histidine cluster (HisC). HisC aggregation is facilitated by Dishevelled and depends on accumulation of Naked/NKD during prolonged Wnt stimulation. Naked/NKD HisC cores co-aggregate with a conserved histidine cluster within Axin, to destabilize it along with Dishevelled, possibly via the autophagy receptor p62, which binds to HisC aggregates. Consistent with this, attenuated Wnt responses are observed in CRISPR-engineered flies and human epithelial cells whose Naked/NKD HisC has been deleted. Thus, HisC aggregation by Naked/NKD provides context-dependent feedback control of prolonged Wnt responses.

Indexed as

AnimalsAxin ProteinDrosophila melanogasterDrosophila ProteinsFeedbackHistidineLarvaWnt Signaling PathwayAxin ProteinAxn protein, DrosophilaDrosophila ProteinsHistidinenkd protein, DrosophilaAxin degradationbiochemistrycell biologychemical biologyDishevelledD. melanogasterfeedback controlhistidine clusterNaked/NKDp62 autophagy receptor

Identifiers

PMID33025907
PMCPMC7581431

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Registered trials

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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.