Evidence map›Paper›PMID 28986324›Full record

ArticleNeurobiology of disease2018

The ubiquitin conjugating enzyme Ube2W regulates solubility of the Huntington's disease protein, huntingtin.

Bo Wang, Li Zeng, Sean A Merillat, Svetlana Fischer, Joseph Ochaba, Leslie M Thompson, Sami J Barmada, Kenneth M Scaglione, Henry L Paulson

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Neurobiology of disease, 2018. 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
1.6field-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.

  1. Article
  2. Review
  3. Article
  4. Ubiquitin-modifying enzymes in Huntington's disease.Frontiers in molecular biosciences · 2023
    Review
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  7. Article
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  11. Article
  12. Protein Misfolding and ER Stress in Huntington's Disease.Frontiers in molecular biosciences · 2019
    Review
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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

9 authors at 3 institutions in 2 countries.

Bo WangDepartment of Neurology, University of Michigan, Ann Arbor, MI 48109, USA; Neuroscience Program, University of Michigan, Ann Arbor, MI 48109, USA; Department of Dermatology, Ruijin Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China.
Li ZengDepartment of Neurology, University of Michigan, Ann Arbor, MI 48109, USA; Department of Neurology, Sichuan Provincial Academy of Medical Sciences and Sichuan Provincial People's Hospital, Chengdu, China.
Sean A MerillatDepartment of Neurology, University of Michigan, Ann Arbor, MI 48109, USA.
Svetlana FischerDepartment of Neurology, University of Michigan, Ann Arbor, MI 48109, USA.
Joseph OchabaDepartment of Neurobiology and Behavior, Institute of Memory Impairment and Neurological Disorders, University of California, Irvine, CA 92697, USA; Department of Psychiatry and Human Behavior, Institute of Memory Impairment and Neurological Disorders, University of California, Irvine, CA 92697, USA.
Leslie M ThompsonDepartment of Neurobiology and Behavior, Institute of Memory Impairment and Neurological Disorders, University of California, Irvine, CA 92697, USA; Department of Psychiatry and Human Behavior, Institute of Memory Impairment and Neurological Disorders, University of California, Irvine, CA 92697, USA.
Sami J BarmadaDepartment of Neurology, University of Michigan, Ann Arbor, MI 48109, USA.
Kenneth M ScaglioneNeuroscience Research Center and Department of Biochemistry, Medical College of Wisconsin, Milwaukee, WI 53226, USA.
Henry L PaulsonDepartment of Neurology, University of Michigan, Ann Arbor, MI 48109, USA; Neuroscience Program, University of Michigan, Ann Arbor, MI 48109, USA. Electronic address: henryp@med.umich.edu.
University of Michigan · USUniversity of California, Irvine · USMedical College of Wisconsin · US

Funding

Michigan Alzheimer's Disease Core CenterP30AG053760 · NIA · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI ROBERTS, SCOTT · 2016 to 2020
$10.1M
Mechanisms of Polyglutamine NeurodegenerationR01NS038712 · NINDS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI PAULSON, HENRY L · 2000 to 2019
$8.1M
RNA decay in amyotrophic lateral sclerosis and frontotemporal lobar degenerationR01NS097542 · NINDS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI BARMADA, SAMI · 2016 to 2025
$3.8M
Neuroregulatory Mechanisms of PIAS1 and Implications for Huntington's DiseaseR01NS090390 · NINDS · UNIVERSITY OF CALIFORNIA-IRVINE · PI DAVIDSON, BEVERLY L., THOMPSON, LESLIE MICHELS · 2015 to 2018
$1.8M
Integrating Quality Control: Studies of CHIP in Age-related NeurodegenerationR01AG034228 · NIA · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI PAULSON, HENRY L · 2009 to 2013
$1.5M
Protein fate in neurodegeneration: Investigations of novel regulatory mechanismsR00NS073936 · NINDS · MEDICAL COLLEGE OF WISCONSIN · PI SCAGLIONE, KENNETH MATTHEW · 2014 to 2016
$741k
Protein fate in neurodegeneration: Investigations of novel regulatory mechanismsK99NS073936 · NINDS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI SCAGLIONE, KENNETH MATTHEW · 2012 to 2013
$197k
NIA NIH HHS P30 AG053760NIA NIH HHS R01 AG034228NINDS NIH HHS K99 NS073936NINDS NIH HHS R00 NS073936NINDS NIH HHS R01 NS038712NINDS NIH HHS R01 NS090390NINDS NIH HHS R01 NS097542
6 · The paper itself

Abstract

Huntington's disease (HD) is caused by a CAG repeat expansion that encodes a polyglutamine (polyQ) expansion in the HD disease protein, huntingtin (HTT). PolyQ expansion promotes misfolding and aggregation of mutant HTT (mHTT) within neurons. The cellular pathways, including ubiquitin-dependent processes, by which mHTT is regulated remain incompletely understood. Ube2W is the only ubiquitin conjugating enzyme (E2) known to ubiquitinate substrates at their amino (N)-termini, likely favoring substrates with disordered N-termini. By virtue of its N-terminal polyQ domain, HTT has an intrinsically disordered amino terminus. In studies employing immortalized cells, primary neurons and a knock-in (KI) mouse model of HD, we tested the effect of Ube2W deficiency on mHTT levels, aggregation and neurotoxicity. In cultured cells, deficiency of Ube2W activity markedly decreases mHTT aggregate formation and increases the level of soluble monomers, while reducing mHTT-induced cytotoxicity. Consistent with this result, the absence of Ube2W in HdhQ200 KI mice significantly increases levels of soluble monomeric mHTT while reducing insoluble oligomeric species. This study sheds light on the potential function of the non-canonical ubiquitin-conjugating enzyme, Ube2W, in this polyQ neurodegenerative disease.

Indexed as

AnimalsCorpus StriatumDisease Models, AnimalGene Knock-In TechniquesHEK293 CellsHumansHuntingtin ProteinHuntington DiseaseInclusion BodiesMaleMice, Inbred C57BLMice, KnockoutNeuronsPrimary Cell CultureUbiquitin-Conjugating EnzymesHtt protein, mouseHuntingtin ProteinUBE2W protein, mouseUbiquitin-Conjugating EnzymesHuntingtinHuntington's diseaseNeurodegenerationProtein misfoldingUbe2WUbiquitinationUbiquitin-conjugating enzyme

Identifiers

PMID28986324
PMCPMC5973538
OpenAlexW2760914811

What OpenQuestion holds

Textmetadata
LicenceTDM
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.