Evidence map›Paper›PMID 29362455›Full record

ArticleScientific reports2018

Dynamic recruitment of ubiquitin to mutant huntingtin inclusion bodies.

Katrin Juenemann, Anne H P Jansen, Luigi van Riel, Remco Merkx, Monique P C Mulder, Heeseon An, Alexander Statsyuk, Janine Kirstein, Huib Ovaa, Eric A Reits

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
23citing papers in PubMed, 1 pooled it
2.3field-weighted citation impact, top 12% 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

23 citing papers in PubMed, 1 synthesis or guideline pooled it, 37 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Article
  4. Prevention of ubiquitination at K6 and K9 in mutant huntingtin exacerbates disease pathology in a knock-in mouse model.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  5. Article
  6. Article
  7. Review
  8. Review
  9. Review
  10. Article
  11. Article
  12. Ubiquitin-modifying enzymes in Huntington's disease.Frontiers in molecular biosciences · 2023
    Review
  13. Article
  14. Article
  15. Article
  16. Article
  17. Article
  18. Assay Systems for Profiling Deubiquitinating Activity.International journal of molecular sciences · 2020
    Review
  19. Article
  20. 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

10 authors at 5 institutions in 3 countries.

Katrin JuenemannDepartment of Medical Biology, Academic Medical Center, 1105 AZ, Amsterdam, The Netherlands.
Anne H P JansenDepartment of Medical Biology, Academic Medical Center, 1105 AZ, Amsterdam, The Netherlands.
Luigi van RielDepartment of Medical Biology, Academic Medical Center, 1105 AZ, Amsterdam, The Netherlands.
Remco MerkxNetherlands Cancer Institute, 1066 CX, Amsterdam, The Netherlands.
Monique P C MulderNetherlands Cancer Institute, 1066 CX, Amsterdam, The Netherlands.
Heeseon AnDepartment of Cell Biology, Harvard Medical School, Boston, MA, 02115, USA.
Alexander StatsyukDepartment of Pharmacological and Pharmaceutical Sciences, University of Houston, Houston, Texas, TX, 77204, USA.
Janine KirsteinLeibniz-Forschungsinstitut für Molekulare Pharmakologie, 13125, Berlin, Germany.
Huib OvaaNetherlands Cancer Institute, 1066 CX, Amsterdam, The Netherlands.
Eric A ReitsDepartment of Medical Biology, Academic Medical Center, 1105 AZ, Amsterdam, The Netherlands. e.a.reits@amc.uva.nl.
Academic Medical Center · NLLeibniz-Forschungsinstitut für Molekulare Pharmakologie · DEThe Netherlands Cancer Institute · NLUniversity of Houston · USLeiden University Medical Center · NL

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Many neurodegenerative diseases, such as Huntington's disease, are hallmarked by the formation of intracellular inclusion bodies (IBs) that are decorated with ubiquitin, proteasomes and chaperones. The apparent enrichment of ubiquitin and components involved in protein quality control at IBs suggests local ubiquitin-dependent enzymatic activity. In this study, we examine recruitment of ubiquitin to IBs of polyglutamine-expanded huntingtin fragments (mHtt) by using synthesized TAMRA-labeled ubiquitin moieties. We show that intracellular TAMRA-ubiquitin is dynamic at mHtt IBs and is incorporated into poly-ubiquitin chains of intracellular substrates, such as mHtt, in a conjugation-dependent manner. Furthermore, we report that mHtt IBs recruit catalytically active enzymes involved in (de)-ubiquitination processes based on novel activity-based probes. However, we also find that the overexpression of the GFP-ubiquitin reporter, unlike the endogenous ubiquitin and TAMRA-ubiquitin, becomes irreversibly sequestered as a ring-like structure around the mHtt IBs, suggesting a methodical disadvantage of GFP-tagged ubiquitin. Our data provide supportive evidence for dynamic recruitment of ubiquitin and ubiquitin (de)-conjugating activity at mHtt initiated IBs.

Indexed as

MutationAnimalsCatalysisCell LineCytoplasmHumansHuntingtin ProteinInclusion BodiesMiceRatsRhodaminesUbiquitinUbiquitination5-carboxytetramethylrhodamine succinimidyl esterHTT protein, humanHuntingtin ProteinRhodaminesUbiquitin

Identifiers

PMID29362455
PMCPMC5780509
OpenAlexW2792900873

What OpenQuestion holds

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LicenceCC BY
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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.