title: It's all about talking: two-way communication between proteasomal and lysosomal degradation pathways via ubiquitin.
abstract: Selective degradation of proteins requires a fine-tuned coordination of the two major proteolytic pathways, the ubiquitin-proteasome system (UPS) and autophagy. Substrate selection and proteolytic activity are defined by a plethora of regulatory cofactors influencing each other. Both proteolytic pathways are initiated by ubiquitylation to mark substrate proteins for degradation, although the size and/or topology of the modification are different. In this context E3 ubiquitin ligases, ensuring the covalent attachment of activated ubiquitin to the substrate, are of special importance. The regulation of E3 ligase activity, competition between different E3 ligases for binding E2 conjugation enzymes and substrates, as well as their interplay with deubiquitylating enzymes (DUBs) represent key events in the cross talk between the UPS and autophagy. The coordination between both degradation routes is further influenced by heat shock factors and ubiquitin-binding proteins (UBPs) such as p97, p62, or optineurin. Mutations in enzymes and ubiquitin-binding proteins or a general decline of both proteolytic systems during aging result in accumulation of damaged and aggregated proteins. Thus further mechanistic understanding of how UPS and autophagy communicate might allow therapeutic intervention especially against age-related diseases.
authors.affiliation: Institute for Genetics and Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne, Germany.
authors.forename: Martina P
authors.initials: MP
authors.lastname: Liebl
authors.affiliation: Institute for Genetics and Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne, Germany thorsten.hoppe@uni-koeln.de.
authors.forename: Thorsten
authors.initials: T
authors.lastname: Hoppe
mesh_terms: D001343:Autophagy / Q000502:physiology; D002352:Carrier Proteins / Q000378:metabolism; D006801:Humans; D008247:Lysosomes / Q000378:metabolism*; D053858:Metabolic Networks and Pathways / Q000502:physiology; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D059748:Proteolysis; D025801:Ubiquitin / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism
chemical_list: D002352:Carrier Proteins; D025801:Ubiquitin; D044767:Ubiquitin-Protein Ligases; D046988:Proteasome Endopeptidase Complex
keywords: UPS; aging; autophagy; proteasome; proteostasis; ubiquitin