ArticleAutophagy2019
Redundancy of human ATG4 protease isoforms in autophagy and LC3/GABARAP processing revealed in cells.
Article in Autophagy, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 140 papers, 1 of them a synthesis that pooled 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.
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.
Who cites it
140 citing papers in PubMed, 1 synthesis or guideline pooled it, 233 citations in OpenAlex.
- Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)Autophagy · 2021Guideline
- The ATG4 isotype is a key regulator in CSE/HGenes & diseases · 2027Article
- The ROCK1 PHC1 domain mediates recruitment to Rho activity zones and contractility signaling.Life science alliance · 2026Article
- Canonical and noncanonical autophagy in immunity.Immunity · 2026Review
- Lipid-gated vesicular trafficking directs HSPA1A to the plasma membrane through the endo-lysosomal network.Cell stress & chaperones · 2026Article
- Dual targeting of SLC6A14 and autophagy/macropinocytosis enhances therapeutic efficacy in pancreatic ductal adenocarcinoma.The Biochemical journal · 2026Article
- Review
- Regulatory mechanisms of post-translational modifications on autophagic flux in neurons following ischemic stroke.Molecular biology reports · 2026Review
- Autophagic Pathway on GABARAP Involved in GABANeurochemical research · 2026Review
- Pharmacological restoration of impaired autophagy in retinal ganglion cells prevents abnormal mitochondrial accumulation and glaucomatous neurodegeneration.Molecular neurodegeneration · 2026Article
- TDP-43: [GU]-ardian of the transcriptome.Molecular neurodegeneration · 2026Review
- The Small Molecule H89 Facilitates Mesenchymal Stem Cell-derived Extracellular Vesicle Release and Optimizes Therapeutic Efficacy in Liver Regeneration.Journal of extracellular vesicles · 2026Article
- Lactate treatment improves brain biochemistry and cognitive function in transgenic Alzheimer's and wild-type mice.Scientific reports · 2026Article
- Article
- Specificity and recognition of the ADP-ribosyl-ubiquitin modification in the DNA damage response.PLoS biology · 2026Article
- Nuclear Localization of Effector BPE159: A Pivotal Mechanism for Intracellular Persistence ofMicroorganisms · 2026Article
- ATG4B is required for mTORC1-mediated anabolic activity and is associated with clinical outcomes in non-small cell lung cancer.FEBS open bio · 2026Article
- Spatially Resolved Multiomics Reveals Metabolic Remodeling and Autophagy Activation in Adamantinomatous Craniopharyngiomas.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- U2AF2 controls alternative splicing in speckle-proximal regions in an RS domain-dependent manner.Nucleic acids research · 2026Article
- Rapid optogenetic manipulation of autophagy reveals that the nuclear pore complex is a robust autophagy substrate.bioRxiv : the preprint server for biology · 2026Article
80 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Macroautophagy/autophagy is a cellular degradation pathway that delivers cytoplasmic material to lysosomes via double-membrane organelles called autophagosomes. Lipidation of ubiquitin-like LC3/GABARAP proteins on the autophagosome membrane is important for autophagy. The cysteine protease ATG4 executes 2 LC3/GABARAP processing events: priming of newly synthesized pro-LC3/GABARAP to enable subsequent lipidation, and delipidation/deconjugation of lipidated LC3/GABARAP (the exact purpose of which is unclear in mammals). Four ATG4 isoforms (ATG4A to ATG4D) exist in mammals; however, the functional redundancy of these proteins in cells is poorly understood. Here we show that human HAP1 and HeLa cells lacking ATG4B exhibit a severe but incomplete defect in LC3/GABARAP processing and autophagy. By further genetic depletion of ATG4 isoforms using CRISPR-Cas9 and siRNA we uncover that ATG4A, ATG4C and ATGD all contribute to residual priming activity, which is sufficient to enable lipidation of endogenous GABARAPL1 on autophagic structures. We also demonstrate that expressing high levels of pre-primed LC3B in ATG4-deficient cells can rescue a defect in autophagic degradation of the cargo receptor SQSTM1/p62, suggesting that delipidation by human ATG4 is not essential for autophagosome formation and fusion with lysosomes. Overall, our study provides a comprehensive characterization of ATG4 isoform function during autophagy in human cells. Abbreviations: Atg: autophagy-related; baf A1: bafilomycin A
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.