Evidence map›Paper›PMID 29458288›Full record

ArticleAutophagy2018

Delipidation of mammalian Atg8-family proteins by each of the four ATG4 proteases.

Karlina J Kauffman, Shenliang Yu, Jiaxin Jin, Brian Mugo, Nathan Nguyen, Aidan O'Brien, Shanta Nag, Alf Håkon Lystad, Thomas J Melia

Open access · bronzeAbstract read
In one paragraph

Article in Autophagy, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers.

0numbers the graph read from it
0cells of the map it votes in
62citing papers in PubMed
9.1field-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

62 citing papers in PubMed, 99 citations in OpenAlex.

  1. Emerging mechanisms of ATG8-independent non-canonical autophagy.Journal of physiology and biochemistry · 2026
    Review
  2. Review
  3. Autophagy · 2026
    Review
  4. Autophagy · 2026
    Article
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2 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

9 authors at 3 institutions in 3 countries.

Karlina J Kauffmana Department of Cell Biology , Yale University School of Medicine , New Haven , CT , USA.
Shenliang Yua Department of Cell Biology , Yale University School of Medicine , New Haven , CT , USA.
Jiaxin Jina Department of Cell Biology , Yale University School of Medicine , New Haven , CT , USA.
Brian Mugoa Department of Cell Biology , Yale University School of Medicine , New Haven , CT , USA.
Nathan Nguyena Department of Cell Biology , Yale University School of Medicine , New Haven , CT , USA.
Aidan O'Briena Department of Cell Biology , Yale University School of Medicine , New Haven , CT , USA.
Shanta Naga Department of Cell Biology , Yale University School of Medicine , New Haven , CT , USA.
Alf Håkon Lystadc Department of Molecular Medicine , Institute of Basic Medical Sciences, University of Oslo , Norway.
Thomas J Meliaa Department of Cell Biology , Yale University School of Medicine , New Haven , CT , USA.
Yale University · USLanzhou University · CNUniversity of Oslo · NO

Funding

Skill Development for Diverse Scientific Careers: A New Course Predoctoral Program in Cellular and Molecular BiologyT32GM007223 · NIGMS · YALE UNIVERSITY · PI BASERGA, SUSAN J · 1985 to 2019
$31.0M
Regulation of Autophagosome Membrane Dynamics by the AtgB Family of ProteinsR01GM100930 · NIGMS · YALE UNIVERSITY · PI MELIA, THOMAS JAMES · 2013 to 2024
$5.4M
Autophagy and NeurodegenerationR01NS063973 · NINDS · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI MELIA, THOMAS JAMES, YAMAMOTO, AI · 2008 to 2019
$3.8M
NIGMS NIH HHS R01 GM100930NIGMS NIH HHS T32 GM007223NINDS NIH HHS R01 NS063973
6 · The paper itself

Abstract

During macroautophagy/autophagy, mammalian Atg8-family proteins undergo 2 proteolytic processing events. The first exposes a COOH-terminal glycine used in the conjugation of these proteins to lipids on the phagophore, the precursor to the autophagosome, whereas the second releases the lipid. The ATG4 family of proteases drives both cleavages, but how ATG4 proteins distinguish between soluble and lipid-anchored Atg8 proteins is not well understood. In a fully reconstituted delipidation assay, we establish that the physical anchoring of mammalian Atg8-family proteins in the membrane dramatically shifts the way ATG4 proteases recognize these substrates. Thus, while ATG4B is orders of magnitude faster at processing a soluble unprimed protein, all 4 ATG4 proteases can be activated to similar enzymatic activities on lipid-attached substrates. The recognition of lipidated but not soluble substrates is sensitive to a COOH-terminal LIR motif both in vitro and in cells. We suggest a model whereby ATG4B drives very fast priming of mammalian Atg8 proteins, whereas delipidation is inherently slow and regulated by all ATG4 homologs.

Indexed as

Adaptor Proteins, Signal TransducingAmino Acid SequenceAnimalsAutophagy-Related Protein 8 FamilyCell MembraneCysteine EndopeptidasesHumansLipidsMammalsMiceMicrotubule-Associated ProteinsSolubilityStatic ElectricitySubstrate SpecificityAdaptor Proteins, Signal TransducingAutophagy-Related Protein 8 FamilyCysteine EndopeptidasesGABARAPL1 protein, humanLipidsMicrotubule-Associated ProteinsATG4delipidationinterfacial regulationLC3-interacting regionRavZ

Identifiers

PMID29458288
PMCPMC6103404
OpenAlexW2800318609

What OpenQuestion holds

Textmetadata
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.