Dataset Information

ATG8-Binding UIM Proteins Define a New Class of Autophagy Adaptors and Receptors.

ABSTRACT: During autophagy, vesicle dynamics and cargo recruitment are driven by numerous adaptors and receptors that become tethered to the phagophore through interactions with lipidated ATG8/LC3 decorating the expanding membrane. Most currently described ATG8-binding proteins exploit a well-defined ATG8-interacting motif (AIM, or LC3-interacting region [LIR]) that contacts a hydrophobic patch on ATG8 known as the LIR/AIM docking site (LDS). Here we describe a new class of ATG8 interactors that exploit ubiquitin-interacting motif (UIM)-like sequences for high-affinity binding to an alternative ATG8 interaction site. Assays with candidate UIM-containing proteins together with unbiased screens identified a large collection of UIM-based ATG8 interactors in plants, yeast, and humans. Analysis of a subset also harboring ubiquitin regulatory X (UBX) domains revealed a role for UIM-directed autophagy in clearing non-functional CDC48/p97 complexes, including some impaired in human disease. With this new class of adaptors and receptors, we greatly extend the reach of selective autophagy and identify new factors regulating autophagic vesicle dynamics.

SUBMITTER: Marshall RS

PROVIDER: S-EPMC6810650 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature

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ATG8-Binding UIM Proteins Define a New Class of Autophagy Adaptors and Receptors.

Marshall Richard S RS Hua Zhihua Z Mali Sujina S McLoughlin Fionn F Vierstra Richard D RD

Cell 20190404 3

During autophagy, vesicle dynamics and cargo recruitment are driven by numerous adaptors and receptors that become tethered to the phagophore through interactions with lipidated ATG8/LC3 decorating the expanding membrane. Most currently described ATG8-binding proteins exploit a well-defined ATG8-interacting motif (AIM, or LC3-interacting region [LIR]) that contacts a hydrophobic patch on ATG8 known as the LIR/AIM docking site (LDS). Here we describe a new class of ATG8 interactors that exploit u ...[more]

PMID: 30955882

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Project description:The Atg8-family proteins are subdivided into two subfamilies: the GABARAP and LC3 subfamilies. These proteins, which are major players of the autophagy pathway, present a conserved glycine in their C-terminus necessary for their association to the autophagosome membrane. This family of proteins present multiple roles from autophagy induction to autophagosome-lysosome fusion and have been described to play a role during cancer progression. Indeed, GABARAPs are described to be downregulated in cancers, and high expression has been linked to a good prognosis. Regarding LC3 s, their expression does not correlate to a particular tumor type or stage. The involvement of Atg8-family proteins during cancer, therefore, remains unclear, and it appears that their anti-tumor role may be associated with their implication in selective protein degradation by autophagy but might also be independent, in some cases, of their conjugation to autophagosomes. In this review, we will then focus on the involvement of GABARAP and LC3 subfamilies during autophagy and cancer and highlight the similarities but also the differences of action of each subfamily member.Abbreviations: AIM: Atg8-interacting motif; AMPK: adenosine monophosphate-associated protein kinase; ATG: autophagy-related; BECN1: beclin 1; BIRC6/BRUCE: baculoviral IAP repeat containing 6; BNIP3L/NIX: BCL2 interacting protein 3 like; GABARAP: GABA type A receptor-associated protein; GABARAPL1/2: GABA type A receptor associated protein like 1/2; GABRA/GABAA: gamma-aminobutyric acid type A receptor subunit; LAP: LC3-associated phagocytosis; LMNB1: lamin B1; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; MTOR: mechanistic target of rapamycin kinase; PI4K2A/PI4KIIα: phosphatidylinositol 4-kinase type 2 alpha; PLEKHM1: plecktrin homology and RUN domain containing M1; PtdIns3K-C1: class III phosphatidylinositol 3-kinase complex 1; SQSTM1: sequestosome 1; ULK1: unc51-like autophagy activating kinase 1.

Dataset Information

ATG8-Binding UIM Proteins Define a New Class of Autophagy Adaptors and Receptors.

Publications

ATG8-Binding UIM Proteins Define a New Class of Autophagy Adaptors and Receptors.

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