title: Functions of the 19S complex in proteasomal degradation.
abstract: The 26S proteasome degrades ubiquitylated proteins. It consists of the 20S proteasome and the PA700/19S complex. PA700 plays essential roles in processing ubiquitylated substrates; it can bind, deubiquitylate, and unfold ubiquitylated proteins, which then translocate into the proteolytic chamber of the 20S proteasome for degradation. Here, we summarize the current knowledge of PA700-mediated substrate binding and deubiquitylation, and provide models to explain how substrate binding and deubiquitylation could regulate proteasomal degradation. We also discuss the features and potential therapeutic uses of the two recently identified small molecule inhibitors of the proteasome-residing deubiquitylating enzymes.
authors.affiliation: Department of Biochemistry and Molecular Genetics, University of Colorado School of Medicine, 12801 E. 17th Ave, Aurora, CO 80045, USA. changwei.liu@ucdenver.edu
authors.forename: Chang-Wei
authors.initials: CW
authors.lastname: Liu
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Jacobson
mesh_terms: D000818:Animals; D006801:Humans; D008958:Models, Molecular; D046988:Proteasome Endopeptidase Complex / Q000737:chemistry* / Q000378:metabolism*; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D059748:Proteolysis; D013379:Substrate Specificity; D025801:Ubiquitin / Q000737:chemistry / Q000378:metabolism; D054875:Ubiquitination
chemical_list: D025801:Ubiquitin; D046988:Proteasome Endopeptidase Complex; C119011:26S proteasome non-ATPase regulatory subunit 13