title: An N-terminal SIAH-interacting motif regulates the stability of the ubiquitin specific protease (USP)-19.
abstract: The Ubiquitin Specific Protease-19 (USP19) regulates cell cycle progression and is involved in the cellular response to different types of stress, including the unfolded protein response (UPR), hypoxia and muscle atrophy. Using the unique N-terminal domain as bait in a yeast-two hybrid screen we have identified the ubiquitin ligases Seven In Absentia Homolog (SIAH)-1 and SIAH2 as binding partners of USP19. The interaction is mediated by a SIAH-consensus binding motif and promotes USP19 ubiquitylation and proteasome-dependent degradation. These findings identify USP19 as a common substrate of the SIAH ubiquitin ligases.
authors.affiliation: Department of Cell and Molecular Biology, Karolinska Institutet, 171 77 Stockholm, Sweden.
authors.forename: Kelly
authors.initials: K
authors.lastname: Velasco
authors.forename: Bin
authors.initials: B
authors.lastname: Zhao
authors.forename: Simone
authors.initials: S
authors.lastname: Callegari
authors.forename: Mikael
authors.initials: M
authors.lastname: Altun
authors.forename: Haiyin
authors.initials: H
authors.lastname: Liu
authors.forename: Gerco
authors.initials: G
authors.lastname: Hassink
authors.forename: Maria G
authors.initials: MG
authors.lastname: Masucci
authors.forename: Kristina
authors.initials: K
authors.lastname: Lindsten
mesh_terms: D020816:Amino Acid Motifs; D015153:Blotting, Western; D019295:Computational Biology / Q000379:methods; D010450:Endopeptidases / Q000235:genetics / Q000378:metabolism*; D004795:Enzyme Stability; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D047468:Immunoprecipitation; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D011485:Protein Binding; D025941:Protein Interaction Mapping; D059748:Proteolysis; D020798:Two-Hybrid System Techniques; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism*; D054875:Ubiquitination; D000098563:Seven in Absentia Proteins
chemical_list: D009687:Nuclear Proteins; D044767:Ubiquitin-Protein Ligases; D000098563:Seven in Absentia Proteins; D010450:Endopeptidases; C559917:USP19 protein, human; D046988:Proteasome Endopeptidase Complex