Evidence map›Paper›PMID 35264151›Full record

ArticleBMC biology2022

Ubiquitylation is required for the incorporation of the Notch receptor into intraluminal vesicles to prevent prolonged and ligand-independent activation of the pathway.

Björn Schnute, Hideyuki Shimizu, Marvin Lyga, Martin Baron, Thomas Klein

Open access · goldAbstract read
In one paragraph

Article in BMC biology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
0.3field-weighted citation impact, top 46% 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

3 citing papers in PubMed, 4 citations in OpenAlex.

  1. Review
  2. Article
  3. Review
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 at 2 institutions in 2 countries.

Björn SchnuteInstitute of Genetics, Heinrich-Heine-University Duesseldorf, Universitaetsstr. 1, 40225, Duesseldorf, Germany.
Hideyuki ShimizuSchool of Biological Sciences, University of Manchester, Michael Smith Building, Oxford Road, Manchester, M13 9PT, UK.
Marvin LygaInstitute of Genetics, Heinrich-Heine-University Duesseldorf, Universitaetsstr. 1, 40225, Duesseldorf, Germany.
Martin BaronSchool of Biological Sciences, University of Manchester, Michael Smith Building, Oxford Road, Manchester, M13 9PT, UK.
Thomas KleinInstitute of Genetics, Heinrich-Heine-University Duesseldorf, Universitaetsstr. 1, 40225, Duesseldorf, Germany. thomas.klein@hhu.de.ORCID 0000-0002-2719-9617
Heinrich Heine University Düsseldorf · DEUniversity of Manchester · GB

Funding

Biotechnology and Biological Sciences Research Council BB/C503162/1Biotechnology and Biological Sciences Research Council BB/E002285/1Biotechnology and Biological Sciences Research Council BB/H000976/1
6 · The paper itself

Abstract

backgroundUbiquitylation of the ligands and the receptor plays an important part in the regulation of the activity of the evolutionary conserved Notch signalling pathway. However, its function for activation of Notch is not completely understood, despite the identification of several E3 ligases devoted to the receptor.

resultsHere we analysed a variant of the Notch receptor where all lysines in its intracellular domain are replaced by arginines. Our analysis of this variant revealed that ubiquitylation of Notch is not essential for its endocytosis. We identified two functions for ubiquitylation of lysines in the Notch receptor. First, it is required for the degradation of free Notch intracellular domain (NICD) in the nucleus, which prevents a prolonged activation of the pathway. More importantly, it is also required for the incorporation of Notch into intraluminal vesicles of maturing endosomes to prevent ligand-independent activation of the pathway from late endosomal compartments.

conclusionsThe findings clarify the role of lysine-dependent ubiquitylation of the Notch receptor and indicate that Notch is endocytosed by several independent operating mechanisms.

Indexed as

Drosophila ProteinsReceptors, NotchEndocytosisLigandsSignal TransductionUbiquitinationUbiquitin-Protein LigasesDrosophila ProteinsLigandsReceptors, NotchUbiquitin-Protein LigasesDxE3-ligaseEndocytosisItchNotch signallingSu(dx)Ubiquitylation

Identifiers

PMID35264151
PMCPMC8908686
OpenAlexW4220757586

What Socratic holds

Textmetadata
LicenceCC BY
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 Socratic graph.