title: The deubiquitinating enzyme USP36 controls selective autophagy activation by ubiquitinated proteins.
abstract: Initially described as a nonspecific degradation process induced upon starvation, autophagy is now known also to be involved in the degradation of specific ubiquitinated substrates such as mitochondria, bacteria and aggregated proteins, ensuring crucial functions in cell physiology and immunity. We report here that the deubiquitinating enzyme USP36 controls selective autophagy activation in Drosophila and in human cells. We show that dUsp36 loss of function autonomously inhibits cell growth while activating autophagy. Despite the phenotypic similarity, dUSP36 is not part of the TOR signaling pathway. Autophagy induced by dUsp36 loss of function depends on p62/SQSTM1, an adaptor for delivering cargo marked by polyubiquitin to autophagosomes. Consistent with p62 requirement, dUsp36 mutant cells display nuclear aggregates of ubiquitinated proteins, including Histone H2B, and cytoplasmic ubiquitinated proteins; the latter are eliminated by autophagy. Importantly, USP36 function in p62-dependent selective autophagy is conserved in human cells. Our work identifies a novel, crucial role for a deubiquitinating enzyme in selective autophagy.
authors.affiliation: CEA/Institut de Recherches en Technologies et Sciences pour le Vivant, Laboratoire de Biologie à Grande Echelle, Grenoble, France. emmanuel.taillebourg@cea.fr
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Taillebourg
authors.forename: Isabel
authors.initials: I
authors.lastname: Gregoire
authors.forename: Perrine
authors.initials: P
authors.lastname: Viargues
authors.forename: Anne-Claire
authors.initials: AC
authors.lastname: Jacomin
authors.forename: Dominique
authors.initials: D
authors.lastname: Thevenon
authors.forename: Mathias
authors.initials: M
authors.lastname: Faure
authors.forename: Marie-Odile
authors.initials: MO
authors.lastname: Fauvarque
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000818:Animals; D001343:Autophagy; D002467:Cell Nucleus / Q000378:metabolism; D049109:Cell Proliferation; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000166:cytology* / Q000201:enzymology*; D010450:Endopeptidases / Q000378:metabolism*; D004789:Enzyme Activation; D005216:Fat Body / Q000166:cytology / Q000378:metabolism; D020868:Gene Silencing; D006367:HeLa Cells; D006801:Humans; D007814:Larva / Q000166:cytology / Q000201:enzymology / Q000254:growth & development; D009154:Mutation / Q000235:genetics; D009687:Nuclear Proteins / Q000378:metabolism; D000071456:Sequestosome-1 Protein; D015398:Signal Transduction; D043222:Ubiquitin Thiolesterase / Q000378:metabolism*; D057149:Ubiquitinated Proteins / Q000378:metabolism*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D009687:Nuclear Proteins; C099718:SQSTM1 protein, human; D000071456:Sequestosome-1 Protein; C501066:USP36 protein, human; D057149:Ubiquitinated Proteins; C439909:imd protein, Drosophila; C080596:ref(2)P protein, Drosophila; D010450:Endopeptidases; D043222:Ubiquitin Thiolesterase; C534688:ubiquitin specific protease 36, Drosophila