Evidence map›Paper›PMID 31692446›Full record

ArticleeLife2019

Negative regulation of autophagy by UBA6-BIRC6-mediated ubiquitination of LC3.

Rui Jia, Juan S Bonifacino

Open access · goldAbstract read
In one paragraph

Article in eLife, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers.

0numbers the graph read from it
0cells of the map it votes in
61citing papers in PubMed
7.3field-weighted citation impact, top 2% 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

61 citing papers in PubMed, 102 citations in OpenAlex.

  1. Article
  2. Autophagy · 2026
    Review
  3. The IAP family member BRUCE/BIRC6: an emerging new player in balancing life and death.Apoptosis : an international journal on programmed cell death · 2026
    Review
  4. The emerging importance of UBA6 in ubiquitylation and proteostasis.Nature reviews. Molecular cell biology · 2026
    Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Review
  11. Article
  12. Article
  13. Article
  14. Article
  15. Review
  16. Article
  17. Article
  18. Neddylation modification stabilizes LC3B by antagonizing its ubiquitin-mediated degradation and promoting autophagy in skin.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  19. Article
  20. Article

1 more citing papers are in PubMed but not listed here.

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

2 authors at 1 institution in 1 country.

Rui JiaNeurosciences and Cellular and Structural Biology Division, Eunice Kennedy Shriver National Institute of Child Health and Human Development National Institutes of Health, Bethesda, United States.ORCID 0000-0002-1797-4069
Juan S BonifacinoNeurosciences and Cellular and Structural Biology Division, Eunice Kennedy Shriver National Institute of Child Health and Human Development National Institutes of Health, Bethesda, United States.ORCID 0000-0002-5673-6370
National Institutes of Health · US

Funding

Protein Trafficking In The Endosomal-Lysosomal SystemZIAHD001607 · NICHD · EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT · PI BONIFACINO, JUAN · 2009 to 2025
$48.3M
Intramural NIH HHS ZIA HD001607NICHD NIH HHS ZIA HD001607NIH HHS ZIA HD001607
6 · The paper itself

Abstract

Although the process of autophagy has been extensively studied, the mechanisms that regulate it remain insufficiently understood. To identify novel autophagy regulators, we performed a whole-genome CRISPR/Cas9 knockout screen in H4 human neuroglioma cells expressing endogenous LC3B tagged with a tandem of GFP and mCherry. Using this methodology, we identified the ubiquitin-activating enzyme UBA6 and the hybrid ubiquitin-conjugating enzyme/ubiquitin ligase BIRC6 as autophagy regulators. We found that these enzymes cooperate to monoubiquitinate LC3B, targeting it for proteasomal degradation. Knockout of UBA6 or BIRC6 increased autophagic flux under conditions of nutrient deprivation or protein synthesis inhibition. Moreover, UBA6 or BIRC6 depletion decreased the formation of aggresome-like induced structures in H4 cells, and α-synuclein aggregates in rat hippocampal neurons. These findings demonstrate that UBA6 and BIRC6 negatively regulate autophagy by limiting the availability of LC3B. Inhibition of UBA6/BIRC6 could be used to enhance autophagic clearance of protein aggregates in neurodegenerative disorders.

Indexed as

AutophagyUbiquitinationCell LineGene Expression Regulation, EnzymologicGene Knockout TechniquesGenetic TestingHumansInhibitor of Apoptosis ProteinsMicrotubule-Associated ProteinsProteasome Endopeptidase ComplexProtein Interaction MapsProteolysisUbiquitin-Activating EnzymesBIRC6 protein, humanInhibitor of Apoptosis ProteinsMAP1LC3B protein, humanMicrotubule-Associated ProteinsProteasome Endopeptidase ComplexUBA6 protein, humanUbiquitin-Activating EnzymesautophagyBIRC6cell biologyhumanLC3ratUBA6ubiquitination

Identifiers

PMID31692446
PMCPMC6863627
OpenAlexW2988977920

What OpenQuestion holds

Textmetadata
LicenceCC0
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.