Evidence map›Paper›PMID 31709703›Full record

ArticleEMBO reports2020

TBK1-mediated phosphorylation of LC3C and GABARAP-L2 controls autophagosome shedding by ATG4 protease.

Lina Herhaus, Ramachandra M Bhaskara, Alf Håkon Lystad, Uxía Gestal-Mato, Adriana Covarrubias-Pinto, Florian Bonn, Anne Simonsen, Gerhard Hummer, Ivan Dikic

Open access · hybridAbstract read
In one paragraph

Article in EMBO reports, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers.

0numbers the graph read from it
0cells of the map it votes in
55citing papers in PubMed
8.0field-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

55 citing papers in PubMed, 87 citations in OpenAlex.

  1. Article
  2. Autophagy · 2026
    Review
  3. Review
  4. TBK1 restricts IRGQ-mediated autophagy.Nature communications · 2026
    Article
  5. Article
  6. Review
  7. Article
  8. Review
  9. Article
  10. Article
  11. Article
  12. Article
  13. Review
  14. Review
  15. Review
  16. The Autophagy ReceptorViruses · 2024
    Article
  17. Article
  18. Review
  19. Article
  20. Role of TBK1 Inhibition in Targeted Therapy of Cancer.Mini reviews in medicinal chemistry · 2024
    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

9 authors at 3 institutions in 2 countries.

Lina HerhausInstitute of Biochemistry II, School of Medicine, Goethe University, Frankfurt am Main, Germany.
Ramachandra M BhaskaraDepartment of Theoretical Biophysics, Max Planck Institute of Biophysics, Frankfurt am Main, Germany.
Alf Håkon LystadDepartment of Molecular Medicine, Faculty of Medicine, Institute of Basic Medical Sciences and Centre for Cancer Cell Reprogramming, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
Uxía Gestal-MatoInstitute of Biochemistry II, School of Medicine, Goethe University, Frankfurt am Main, Germany.
Adriana Covarrubias-PintoInstitute of Biochemistry II, School of Medicine, Goethe University, Frankfurt am Main, Germany.
Florian BonnInstitute of Biochemistry II, School of Medicine, Goethe University, Frankfurt am Main, Germany.
Anne SimonsenDepartment of Molecular Medicine, Faculty of Medicine, Institute of Basic Medical Sciences and Centre for Cancer Cell Reprogramming, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.ORCID 0000-0003-4711-7057
Gerhard HummerDepartment of Theoretical Biophysics, Max Planck Institute of Biophysics, Frankfurt am Main, Germany.ORCID 0000-0001-7768-746X
Ivan DikicInstitute of Biochemistry II, School of Medicine, Goethe University, Frankfurt am Main, Germany.ORCID 0000-0001-8156-9511
Goethe University Frankfurt · DEUniversity of Oslo · NOMax Planck Institute of Biophysics · DE

Funding

Deutsche Forschungsgemeinschaft (DFG) SFB1117Kreftforeningen (Norwegian Cancer Society) 171318Max-Planck-Gesellschaft (MPG)MPCDF
6 · The paper itself

Abstract

Autophagy is a highly conserved catabolic process through which defective or otherwise harmful cellular components are targeted for degradation via the lysosomal route. Regulatory pathways, involving post-translational modifications such as phosphorylation, play a critical role in controlling this tightly orchestrated process. Here, we demonstrate that TBK1 regulates autophagy by phosphorylating autophagy modifiers LC3C and GABARAP-L2 on surface-exposed serine residues (LC3C S93 and S96; GABARAP-L2 S87 and S88). This phosphorylation event impedes their binding to the processing enzyme ATG4 by destabilizing the complex. Phosphorylated LC3C/GABARAP-L2 cannot be removed from liposomes by ATG4 and are thus protected from ATG4-mediated premature removal from nascent autophagosomes. This ensures a steady coat of lipidated LC3C/GABARAP-L2 throughout the early steps in autophagosome formation and aids in maintaining a unidirectional flow of the autophagosome to the lysosome. Taken together, we present a new regulatory mechanism of autophagy, which influences the conjugation and de-conjugation of LC3C and GABARAP-L2 to autophagosomes by TBK1-mediated phosphorylation.

Indexed as

AutophagosomesMicrotubule-Associated ProteinsAutophagyAutophagy-Related Protein 8 FamilyHEK293 CellsHeLa CellsHumansPeptide HydrolasesPhosphorylationAutophagy-Related Protein 8 FamilyMicrotubule-Associated ProteinsPeptide HydrolasesATG4ATG8autophagyphosphorylationTBK1

Identifiers

PMID31709703
PMCPMC6945063
OpenAlexW2983605677

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.