Evidence map›Paper›PMID 28821708›Full record

ArticleNature communications2017

A reversible phospho-switch mediated by ULK1 regulates the activity of autophagy protease ATG4B.

N Pengo, A Agrotis, K Prak, J Jones, R Ketteler

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 86 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
86citing papers in PubMed, 1 pooled it
9.7field-weighted citation impact, top 1% 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

86 citing papers in PubMed, 1 synthesis or guideline pooled it, 146 citations in OpenAlex.

  1. Guideline
  2. Autophagy · 2026
    Review
  3. Review
  4. Review
  5. Article
  6. Article
  7. Article
  8. The human autophagy-initiating complexes ULK1C and PI3KC3-C1.The Journal of biological chemistry · 2025
    Review
  9. Review
  10. Article
  11. Article
  12. Article
  13. Circular RNA-Encoded Proteins in Disease Pathogenesis.International journal of biological sciences · 2025
    Review
  14. Article
  15. Article
  16. Physiological functions of ULK1/2.Journal of molecular biology · 2024
    Review
  17. Article
  18. Autophagy Dysfunction: The Kernel of Hair Loss?Clinical, cosmetic and investigational dermatology · 2024
    Review
  19. Article
  20. Article

26 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

5 authors at 1 institution in 1 country.

N PengoMRC Laboratory for Molecular Cell Biology, University College London, Gower Street, London, WC1E 6BT, UK.
A AgrotisMRC Laboratory for Molecular Cell Biology, University College London, Gower Street, London, WC1E 6BT, UK.
K PrakMRC Laboratory for Molecular Cell Biology, University College London, Gower Street, London, WC1E 6BT, UK.
J JonesMRC Laboratory for Molecular Cell Biology, University College London, Gower Street, London, WC1E 6BT, UK.ORCID http://orcid.org/0000-0002-7382-5105
R KettelerMRC Laboratory for Molecular Cell Biology, University College London, Gower Street, London, WC1E 6BT, UK. r.ketteler@ucl.ac.uk.ORCID http://orcid.org/0000-0002-2786-7291
MRC Laboratory for Molecular Cell Biology · GB

Funding

Medical Research Council MC_EX_G0800785Medical Research Council MC_PC_12024
6 · The paper itself

Abstract

Upon induction of autophagy, the ubiquitin-like protein LC3 is conjugated to phosphatidylethanolamine (PE) on the inner and outer membrane of autophagosomes to allow cargo selection and autophagosome formation. LC3 undergoes two processing steps, the proteolytic cleavage of pro-LC3 and the de-lipidation of LC3-PE from autophagosomes, both executed by the same cysteine protease ATG4. How ATG4 activity is regulated to co-ordinate these events is currently unknown. Here we find that ULK1, a protein kinase activated at the autophagosome formation site, phosphorylates human ATG4B on serine 316. Phosphorylation at this residue results in inhibition of its catalytic activity in vitro and in vivo. On the other hand, phosphatase PP2A-PP2R3B can remove this inhibitory phosphorylation. We propose that the opposing activities of ULK1-mediated phosphorylation and PP2A-mediated dephosphorylation provide a phospho-switch that regulates the cellular activity of ATG4B to control LC3 processing.Upon autophagy induction, LC3 is cleaved by the protease ATG4 and conjugated to the autophagosomal membrane; however, its removal is mediated by the same protease. Here the authors show that ULK1-mediated phosphorylation and PP2A-mediated dephosphorylation of ATG4 regulates its cellular activity to control LC3 processing.

Indexed as

AutophagyAmino Acid SequenceAnimalsAutophagosomesAutophagy-Related Protein-1 HomologAutophagy-Related ProteinsBase SequenceBlotting, WesternCells, CulturedCysteine EndopeptidasesHEK293 CellsHeLa CellsHumansMiceMicroscopy, ConfocalMicrotubule-Associated ProteinsATG4B protein, humanAutophagy-Related Protein-1 HomologAutophagy-Related ProteinsCysteine EndopeptidasesMAP1LC3B protein, humanMicrotubule-Associated ProteinsProtein Phosphatase 2Serine

Identifiers

PMID28821708
PMCPMC5562857
OpenAlexW2742831394

What OpenQuestion holds

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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.