title: Paradigms of protein degradation by the proteasome.
abstract: The proteasome is the main proteolytic machine in the cytosol and nucleus of eukaryotic cells where it degrades hundreds of regulatory proteins, removes damaged proteins, and produces peptides that are presented by MHC complexes. New structures of the proteasome particle show how its subunits are arranged and provide insights into how the proteasome is regulated. Proteins are targeted to the proteasome by tags composed of several ubiquitin moieties. The structure of the tags tunes the order in which proteins are degraded. The proteasome itself edits the ubiquitin tags and drugs that interfere in this process can enhance the clearance of toxic proteins from cells. Finally, the proteasome initiates degradation at unstructured regions within its substrates and this step contributes to substrate selection.
authors.affiliation: Frontier Research Core for Life Sciences, University of Toyama, Toyama 930-8555, Japan.
authors.forename: Tomonao
authors.initials: T
authors.lastname: Inobe
authors.affiliation: Department of Molecular Biosciences, The University of Texas at Austin, Austin, TX 78712, USA. Electronic address: matouschek@austin.utexas.edu.
authors.forename: Andreas
authors.initials: A
authors.lastname: Matouschek
mesh_terms: D000818:Animals; D006801:Humans; D008958:Models, Molecular; D046988:Proteasome Endopeptidase Complex / Q000737:chemistry / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism; D059748:Proteolysis; D025801:Ubiquitin / Q000378:metabolism; D054875:Ubiquitination
chemical_list: D011506:Proteins; D025801:Ubiquitin; D046988:Proteasome Endopeptidase Complex