Evidence map›Paper›PMID 27555585›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2016

Hedgehog-dependent E3-ligase Midline1 regulates ubiquitin-mediated proteasomal degradation of Pax6 during visual system development.

Thorsten Pfirrmann, Enrico Jandt, Swantje Ranft, Ashwin Lokapally, Herbert Neuhaus, Muriel Perron, Thomas Hollemann

Abstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
1.2field-weighted citation impact, top 19% 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

16 citing papers in PubMed, 27 citations in OpenAlex.

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  15. Ubiquitylation at the crossroads of development and disease.Nature reviews. Molecular cell biology · 2018
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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

7 authors at 3 institutions in 2 countries.

Thorsten PfirrmannInstitute for Physiological Chemistry, University of Halle-Wittenberg, 06114 Halle, Germany;
Enrico JandtInstitute for Physiological Chemistry, University of Halle-Wittenberg, 06114 Halle, Germany;
Swantje RanftInstitute for Physiological Chemistry, University of Halle-Wittenberg, 06114 Halle, Germany; Gynecological Hospital, University Medical Center Mannheim, 68167 Mannheim, Germany;
Ashwin LokapallyInstitute for Physiological Chemistry, University of Halle-Wittenberg, 06114 Halle, Germany;
Herbert NeuhausInstitute for Physiological Chemistry, University of Halle-Wittenberg, 06114 Halle, Germany;
Muriel PerronParis-Saclay Institute of Neuroscience, CNRS, Univ Paris Sud, Université Paris-Saclay, 91405 Orsay, France.
Thomas HollemannInstitute for Physiological Chemistry, University of Halle-Wittenberg, 06114 Halle, Germany; thomas.hollemann@medizin.uni-halle.de.ORCID 0000-0002-5168-4540
Martin Luther University Halle-Wittenberg · DECentre National de la Recherche Scientifique · FRHeidelberg University · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Pax6 is a key transcription factor involved in eye, brain, and pancreas development. Although pax6 is expressed in the whole prospective retinal field, subsequently its expression becomes restricted to the optic cup by reciprocal transcriptional repression of pax6 and pax2 However, it remains unclear how Pax6 protein is removed from the eyestalk territory on time. Here, we report that Mid1, a member of the RBCC/TRIM E3 ligase family, which was first identified in patients with the X-chromosome-linked Opitz BBB/G (OS) syndrome, interacts with Pax6. We found that the forming eyestalk is a major domain of mid1 expression, controlled by the morphogen Sonic hedgehog (Shh). Here, Mid1 regulates the ubiquitination and proteasomal degradation of Pax6 protein. Accordantly, when Mid1 levels are knocked down, Pax6 expression is expanded and eyes are enlarged. Our findings indicate that remaining or misaddressed Pax6 protein is cleared from the eyestalk region to properly set the border between the eyestalk territory and the retina via Mid1. Thus, we identified a posttranslational mechanism, regulated by Sonic hedgehog, which is important to suppress Pax6 activity and thus breaks pax6 autoregulation at defined steps during the formation of the visual system.

Indexed as

AnimalsEmbryo, NonmammalianEyeEye ProteinsFeedback, PhysiologicalGene Expression Regulation, DevelopmentalHedgehog ProteinsHEK293 CellsHeLa CellsHumansOrganogenesisOrgan SizePAX6 Transcription FactorProteasome Endopeptidase ComplexProteolysisSignal TransductionEye ProteinsHedgehog ProteinsPax6 protein, XenopusPAX6 Transcription FactorProteasome Endopeptidase ComplexShh protein, XenopusUbiquitin-Protein LigasesXenopus Proteinseye developmentmid1pax6ubiquitinXenopus

Identifiers

PMID27555585
PMCPMC5018744
OpenAlexW2514732099

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.