ArticleAutophagy2017
ATG4B contains a C-terminal LIR motif important for binding and efficient cleavage of mammalian orthologs of yeast Atg8.
Article in Autophagy, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 69 papers.
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Who cites it
69 citing papers in PubMed, 99 citations in OpenAlex.
- HFGuidedDesign:Chemical science · 2026Article
- Generation of an autophagy-targeting influenza A virus as live attenuated vaccine.Nature communications · 2026Article
- NCOA4 initiates ferritinophagy by avidly binding GATE16 using two short linear interaction motifs.Life science alliance · 2026Article
- A proteome-wide biochemical screen defines binding determinants of the core autophagy protein LC3B.bioRxiv : the preprint server for biology · 2026Article
- PRDX1 promotes testosterone synthesis and attenuates aging via redox regulation of ATG4B to modulate lipophagy.Nature communications · 2025Article
- Cancer-associated mutations in autophagy-related proteins analyzed in yeast and human cells.Autophagy · 2025Article
- Differential roles of N- and C-terminal LIR motifs in the catalytic activity and membrane targeting of RavZ and ATG4B proteins.BMB reports · 2024Article
- Article
- UBE3C tunes autophagy via ATG4B ubiquitination.Autophagy · 2024Article
- Atg8 family proteins, LIR/AIM motifs and other interaction modes.Autophagy reports · 2023Article
- ATNC: Versatile Nanobody Chimeras for Autophagic Degradation of Intracellular Unligandable and Undruggable Proteins.Journal of the American Chemical Society · 2023Article
- Loss of ATG4B and ATG4A results in two-stage cell cycle defects in pancreatic ductal adenocarcinoma cells.Journal of cell science · 2023Article
- The LC3B FRET biosensor monitors the modes of action of ATG4B during autophagy in living cells.Autophagy · 2023Article
- Semisynthetic LC3 Probes for Autophagy Pathways Reveal a Noncanonical LC3 Interacting Region Motif Crucial for the Enzymatic Activity of Human ATG3.ACS central science · 2023Article
- Article
- ATG4B and pS383/392-ATG4B serve as potential biomarkers and therapeutic targets of colorectal cancer.Cancer cell international · 2023Article
- Nitidine chloride induces cardiac hypertrophy in mice by targeting autophagy-related 4B cysteine peptidase.Acta pharmacologica Sinica · 2023Article
- Bi-allelic ATG4D variants are associated with a neurodevelopmental disorder characterized by speech and motor impairment.NPJ genomic medicine · 2023Article
- Prevention of Bleomycin-Induced Pulmonary Inflammation and Fibrosis in Mice by Bilobalide.Evidence-based complementary and alternative medicine : eCAM · 2023Article
- Structural biology of the Atg8 and Atg12 conjugation systems.Autophagy reports · 2023Review
9 more citing papers are in PubMed but not listed here.
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Authors and funding
12 authors at 2 institutions in 2 countries.
Funding
Abstract
The cysteine protease ATG4B cleaves off one or more C-terminal residues of the inactive proform of proteins of the ortholog and paralog LC3 and GABARAP subfamilies of yeast Atg8 to expose a C-terminal glycine that is conjugated to phosphatidylethanolamine during autophagosome formation. We show that ATG4B contains a C-terminal LC3-interacting region (LIR) motif important for efficient binding to and cleavage of LC3 and GABARAP proteins. We solved the crystal structures of the GABARAPL1-ATG4B C-terminal LIR complex. Analyses of the structures and in vitro binding assays, using specific point mutants, clearly showed that the ATG4B LIR binds via electrostatic-, aromatic HP1 and hydrophobic HP2 pocket interactions. Both these interactions and the catalytic site-substrate interaction contribute to binding between LC3s or GABARAPs and ATG4B. We also reveal an unexpected role for ATG4B in stabilizing the unlipidated forms of GABARAP and GABARAPL1. In mouse embryonic fibroblast (MEF) atg4b knockout cells, GABARAP and GABARAPL1 were unstable and degraded by the proteasome. Strikingly, the LIR motif of ATG4B was required for stabilization of the unlipidated forms of GABARAP and GABARAPL1 in cells.
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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.