title: The ubiquitin specific protease-4 (USP4) interacts with the S9/Rpn6 subunit of the proteasome.
abstract: The proteasome is the major non-lysosomal proteolytic machine in cells that, through degradation of ubiquitylated substrates, regulates virtually all cellular functions. Numerous accessory proteins influence the activity of the proteasome by recruiting or deubiquitylating proteasomal substrates, or by maintaining the integrity of the complex. Here we show that the ubiquitin specific protease (USP)-4, a deubiquitylating enzyme with specificity for both Lys48 and Lys63 ubiquitin chains, interacts with the S9/Rpn6 subunit of the proteasome via an internal ubiquitin-like (UBL) domain. S9/Rpn6 acts as a molecular clamp that holds together the proteasomal core and regulatory sub-complexes. Thus, the interaction with USP4 may regulate the structure and function of the proteasome or the turnover of specific proteasomal substrates.
authors.affiliation: Department of Cell and Molecular Biology, Karolinska Institutet, Box 285, 17177 Stockholm, Sweden.
authors.forename: Bin
authors.initials: B
authors.lastname: Zhao
authors.forename: Kelly
authors.initials: K
authors.lastname: Velasco
authors.forename: Ramakrishna
authors.initials: R
authors.lastname: Sompallae
authors.forename: Thorsten
authors.initials: T
authors.lastname: Pfirrmann
authors.forename: Maria G
authors.initials: MG
authors.lastname: Masucci
authors.forename: Kristina
authors.initials: K
authors.lastname: Lindsten
mesh_terms: D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D046988:Proteasome Endopeptidase Complex / Q000737:chemistry / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D043222:Ubiquitin Thiolesterase / Q000378:metabolism*; D064570:Ubiquitin-Specific Proteases
chemical_list: C486203:USP4 protein, human; D043222:Ubiquitin Thiolesterase; D064570:Ubiquitin-Specific Proteases; D046988:Proteasome Endopeptidase Complex; C119011:26S proteasome non-ATPase regulatory subunit 13