Evidence map›Paper›PMID 31042464›Full record

ArticleCell reports2019

Active Protein Neddylation or Ubiquitylation Is Dispensable for Stress Granule Dynamics.

Sebastian Markmiller, Amit Fulzele, Reneé Higgins, Marilyn Leonard, Gene W Yeo, Eric J Bennett

Abstract read
In one paragraph

Article in Cell reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.

0numbers the graph read from it
0cells of the map it votes in
43citing 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

43 citing papers in PubMed.

  1. Review
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  11. Article
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  13. Proteotoxic stress and the ubiquitin proteasome system.Seminars in cell & developmental biology · 2024
    Review
  14. Article
  15. Article
  16. Review
  17. Review
  18. Review
  19. Review
  20. TheActa biochimica et biophysica Sinica · 2023
    Article
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

6 authors.

Sebastian MarkmillerDepartment of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 92093, USA; Stem Cell Program, University of California, San Diego, La Jolla, CA 92093, USA; Institute for Genomic Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
Amit FulzeleCell and Developmental Biology, Division of Biological Sciences, University of California, San Diego, La Jolla, CA 92093, USA.
Reneé HigginsCell and Developmental Biology, Division of Biological Sciences, University of California, San Diego, La Jolla, CA 92093, USA.
Marilyn LeonardCell and Developmental Biology, Division of Biological Sciences, University of California, San Diego, La Jolla, CA 92093, USA.
Gene W YeoDepartment of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 92093, USA; Stem Cell Program, University of California, San Diego, La Jolla, CA 92093, USA; Institute for Genomic Medicine, University of California, San Diego, La Jolla, CA 92093, USA. Electronic address: geneyeo@ucsd.edu.
Eric J BennettCell and Developmental Biology, Division of Biological Sciences, University of California, San Diego, La Jolla, CA 92093, USA. Electronic address: e1bennett@ucsd.edu.

Funding

Functional RNA elements in the human genomeR01HG004659 · NHGRI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Kevin Daniel Corbett, Eugene Wei-Ming Yeo · 2008 to 2026
$12.4M
Therapeutic strategies for microsatellite expansion diseases using RNA-targeting CRISPR/CasR01NS103172 · NINDS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI MAURICE SCOTT SWANSON, Eugene Wei-Ming Yeo · 2017 to 2026
$5.6M
Manipulating Protein Homeostasis through Specialized Quality Control RibosomesDP2GM119132 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI BENNETT, ERIC J · 2015 to 2015
$2.3M
Leveraging orphan protein degradation pathways to target cells with unstable proteomesR01GM127681 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI BENNETT, ERIC J · 2018 to 2021
$1.2M
NHGRI NIH HHS R01 HG004659NIGMS NIH HHS DP2 GM119132NIGMS NIH HHS R01 GM127681NINDS NIH HHS R01 NS103172
6 · The paper itself

Abstract

Stress granule (SG) formation is frequently accompanied by ubiquitin proteasome system (UPS) impairment and ubiquitylated protein accumulation. SGs, ubiquitin, and UPS components co-localize, but the relationship between the ubiquitin pathway and SGs has not been systematically characterized. We utilize pharmacological inhibition of either the ubiquitin- or NEDD8-activating enzyme (UAE or NAE) to probe whether active ubiquitylation or neddylation modulate SG dynamics. We show that UAE inhibition results in rapid loss of global protein ubiquitylation using ubiquitin-specific proteomics. Critically, inhibiting neither UAE nor NAE significantly affected SG formation or disassembly, indicating that active protein ubiquitylation or neddylation is dispensable for SG dynamics. Using antibodies with varying preference for free ubiquitin or polyubiquitin and fluorescently tagged ubiquitin variants in combination with UAE inhibition, we show that SGs co-localize primarily with unconjugated ubiquitin rather than polyubiquitylated proteins. These findings clarify the role of ubiquitin in SG biology and suggest that free ubiquitin may alter SG protein interactions.

Indexed as

Stress, PhysiologicalUbiquitinationCytoplasmic GranulesHCT116 CellsHEK293 CellsHeLa CellsHumansNEDD8 ProteinProteasome Endopeptidase ComplexUbiquitin-Activating EnzymesNEDD8 ProteinNEDD8 protein, humanProteasome Endopeptidase ComplexUbiquitin-Activating EnzymescentrosomeNedd8neurodegenerationoxidative stressproteasomeprotein aggregationprotein homeostasissodium arsenitestress granuleubiquitin

Identifiers

PMID31042464
PMCPMC6508666

What OpenQuestion holds

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LicenceCC BY-NC-ND
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.